SHORT INTERFERING NUCLEIC ACID (siNA) MOLECULES AND USES THEREOF FOR CORONAVIRUS DISEASES

FIELD OF THE INVENTION

The present invention is in the field of pharmaceutical compounds and preparations and method of their use in the treatment of disease. Described are short interfering nucleic acid (siNA) molecules comprising modified nucleotides, compositions containing the same, and uses thereof for treating or preventing coronavirus infections. In particular, the present invention is in the field of siNA molecules effective against a broad spectrum of coronaviruses, and especially the β-coronaviruses, including SARS-CoV-2, the causative agent of COVID-19.

BACKGROUND

The following discussion is merely provided to aid the reader in understanding the disclosure and is not admitted to describe or constitute prior art thereto.

Coronavirus disease 2019 (COVID-19) (also referred to as novel coronavirus pneumonia or 2019-nCoV acute respiratory disease) is an infectious disease caused by the virus severe respiratory syndrome coronavirus 2 (SARS-CoV-2) (also referred to as novel coronavirus 2019, or 2019-nCoV). The disease was first identified in December 2019 and spread globally, causing a pandemic. Symptoms of COVID-19 include fever, cough, shortness of breath, fatigue, headache, loss of smell, nasal congestion, sore throat, coughing up sputum, pain in muscles or joints, chills, nausea, vomiting, and diarrhea. In severe cases, symptoms can include difficulty waking, confusion, blueish face or lips, coughing up blood, decreased white blood cell count, and kidney failure. Complications can include pneumonia, viral sepsis, acute respiratory distress syndrome, and kidney failure.

COVID-19 is especially threatening to public health. The virus is highly contagious, and studies currently indicate that it can be spread by asymptomatic carriers or by those who are pre-symptomatic. Likewise, the early stage of the disease is slow-progressing enough that carriers do not often realize they are infected, leading them to expose numerous others to the virus. The combination of COVID-19's ease of transmission, its high rate of hospitalization of victims, and its death rate make the virus a substantial public health risk, especially for countries without a healthcare system equipped to provide supportive care to pandemic-level numbers of patients. There is not yet a vaccine or specific antiviral treatment for COVID-19 and accordingly, there is a pressing need for treatments or cures.

SARS-CoV-2 is not the only coronavirus that causes disease. It is a β-coronavirus, a genus of coronaviruses that includes other human pathogens, including SARS-CoV (the causative agent of SARS), MERS-CoV (the causative agent of MERS), and HCoV-OC43 (a causative agent of the common cold). The infectivity of these viruses, and the severity of the diseases they cause, varies widely. B-coronaviruses can also manifest as zoonotic infections, spread to and from humans and animals. Additionally, non-human species such as camels, bats, tigers, non-human primates, and rabbits can be susceptible to β-coronaviruses. Accordingly, there is a pressing need for treatments or cures to multiple coronaviruses.

RNA interference (RNAi) is a biological response to double-stranded RNA that mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes. The short interfering nucleic acids (siNA), such as siRNA, have been developed for RNAi therapy to treat a variety of diseases. For instance, RNAi therapy has been proposed for the treatment of metabolic diseases, neurodegenerative diseases, cancer, and pathogenic infections (See e.g., Rondindone, Biotechniques, 2018, 40(4S), doi.org/10.2144/000112163, Boudreau and Davidson, Curr Top Dev Biol, 2006, 75:73-92, Chalbatani et al., Int J Nanomedicine, 2019, 14:3111-3128, Arbuthnot, Drug News Perspect, 2010, 23(6):341-50, and Chernikov et. al., Front. Pharmacol., 2019, doi.org/10.3389/fphar.2019.00444, each of which are incorporated by reference in their entirety).

The present disclosure provides siNA molecules useful against coronaviruses, and especially SARS-CoV-2, the causative agent of COVID-19. Accordingly, the present disclosure fulfills the need in the art for compounds that can be safely and effectively treat or prevent coronavirus infections in humans.

SUMMARY OF THE INVENTION

Disclosed herein are short interfering nucleic acid (siNA) molecules, which can be used to treat and/or prevent viral disease and infections, such as diseases (e.g., COVID-19) or infections caused by coronavirus like SARS-CoV-2. In some embodiments, the siNA can be a double-stranded siNA (ds-siNA).

In one aspect, the present disclosure provides siNA that comprise (a) a sense strand comprising a first nucleotide sequence, wherein the first nucleotide sequence is 15 to 30 nucleotides in length and comprises a nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to of any one of SEQ ID NOs: 1-1203 and 2411-3392; and (b) an antisense strand comprising a second nucleotide sequence, wherein the second nucleotide sequence is 15 to 30 nucleotides in length and comprises a nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the first nucleotide sequence.

In another aspect, the present disclosure provides siNA that comprise a sense strand comprises (a) a first nucleotide sequence, wherein the first nucleotide sequence is identical to an RNA corresponding to 15 to 30 nucleotides within positions 190-216, 233-279, 288-324, 455-477, 626-651, 704-723, 3352-3378, 5384-5403, 6406-6483, 7532-7551, 9588-9606, 10484-10509, 11609-11630, 11834-11853, 12023-12045, 12212-12234, 12401-12420, 12839-12867, 12885-12924, 12966-12990, 13151-13176, 13363-13386, 13388-13416, 13458-13416, 13458-13520, 13762-13790, 14290-14312, 14404-14429, 14500-14531, 14623-14642, 14650-14687, 14698-14717, 14722-14748, 14750-14777, 14821-14846, 14854-14873, 14875-14903, 14962-14990, 14992-15020, 15055-15140, 15172-15200, 15310-15332, 15346-15367, 15496-15518, 15622-15644, 15838-15869, 15886-15905, 15985-16010, 16057-16079, 16186-16205, 16430-16448, 16822-16865, 16954-16976, 17008-17042, 17080-17111, 17137-17156, 17269-17289, 17530-17549, 17563-17582, 17680-17699, 17746-17765, 17857-17876, 17956-17975, 18100-18122, 18196-18218, 19618-19639, 19783-19802, 19831-19850, 20107-20130, 20776-20795, 21502-21524, 24302-24325, 24446-24465, 24620-24651, 24662-24684, 25034-25057, 25104-25128, 25364-25387, 25502-25530, 26191-26227, 26232-26267, 26269-26330, 26332-26394, 26450-26481, 26574-26600, 27003-27064, 27093-27111, 27183-27212, 27382-27407, 27511-27533, 27771-27818, 28270-28296, 28397-28434, 28513-28546, 28673-28692, 28706-28726, 28744-28794, 28799-28827, 28946-28972, 28976-29034, 29144-29172, 29174-29196, 29228-29259, 29285-29305, 29342-29394, 29444-29463, 29543-29566, 29598-29630, 29652-29687, 29689-29731, 29733-29757, or 29770-29828 of SEQ ID NO: 2407 and (b) an antisense strand.

In another aspect, the present disclosure provides siNA that comprise an antisense strand comprising (a) a second nucleotide sequence, wherein the second nucleotide sequence is complementary to an RNA corresponding to 15 to 30 nucleotides within positions 190-216, 233-279, 288-324, 455-477, 626-651, 704-723, 3352-3378, 5384-5403, 6406-6483, 7532-7551, 9588-9606, 10484-10509, 11609-11630, 11834-11853, 12023-12045, 12212-12234, 12401-12420, 12839-12867, 12885-12924, 12966-12990, 13151-13176, 13363-13386, 13388-13416, 13458-13416, 13458-13520, 13762-13790, 14290-14312, 14404-14429, 14500-14531, 14623-14642, 14650-14687, 14698-14717, 14722-14748, 14750-14777, 14821-14846, 14854-14873, 14875-14903, 14962-14990, 14992-15020, 15055-15140, 15172-15200, 15310-15332, 15346-15367, 15496-15518, 15622-15644, 15838-15869, 15886-15905, 15985-16010, 16057-16079, 16186-16205, 16430-16448, 16822-16865, 16954-16976, 17008-17042, 17080-17111, 17137-17156, 17269-17289, 17530-17549, 17563-17582, 17680-17699, 17746-17765, 17857-17876, 17956-17975, 18100-18122, 18196-18218, 19618-19639, 19783-19802, 19831-19850, 20107-20130, 20776-20795, 21502-21524, 24302-24325, 24446-24465, 24620-24651, 24662-24684, 25034-25057, 25104-25128, 25364-25387, 25502-25530, 26191-26227, 26232-26267, 26269-26330, 26332-26394, 26450-26481, 26574-26600, 27003-27064, 27093-27111, 27183-27212, 27382-27407, 27511-27533, 27771-27818, 28270-28296, 28397-28434, 28513-28546, 28673-28692, 28706-28726, 28744-28794, 28799-28827, 28946-28972, 28976-29034, 29144-29172, 29174-29196, 29228-29259, 29285-29305, 29342-29394, 29444-29463, 29543-29566, 29598-29630, 29652-29687, 29689-29731, 29733-29757, or 29770-29828 of SEQ ID NO: 2407 and (b) a sense strand.

In another aspect, the present disclosure provides siNA that comprise (a) a sense strand comprising a nucleotide sequence identical to an RNA corresponding to any one of SEQ ID NOs: 1-1203 and 2411-3392 and (b) an antisense strand.

In another aspect, the present disclosure provides siNA that comprise (a) an antisense strand comprising a nucleotide sequence identical to an RNA corresponding to any one of SEQ ID NOs: 1204-2406 and 3393-4374 and (b) a sense strand.

In some embodiments, the sense strand can comprise 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end is a 2′-fluoro nucleotide; and the antisense strand can comprise 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide.

In some embodiments, the sense strand can comprise 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and the antisense strand can comprise 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end is a 2′-fluoro nucleotide.

In some embodiments, the sense strand can comprise 16, 17, 18, 19, 20, 21, 22, 23, or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In some embodiments, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotides in the sense strand can be modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide.

In some embodiments, (i) at least 2, 3, 4, 5, or 6 modified nucleotides of the sense strand are 2′-fluoro nucleotides; (ii) no more than 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the sense strand are 2′-fluoro nucleotides; (iii) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 modified nucleotides of the sense strand sequence are 2′-O-methyl nucleotides; and/or (iv) no more than 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the sense strand are 2′-O-methyl nucleotides.

In some embodiments, the antisense strand can comprise 16, 17, 18, 19, 20, 21, 22, 23, or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In some embodiments, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotides in the antisense strand are modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide.

In some embodiments, (i) at least 2, 3, 4, 5, or 6 modified nucleotides of the antisense strand are 2′-fluoro nucleotides; (ii) no more than 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the antisense strand are 2′-fluoro nucleotides; (iii) at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 modified nucleotides of the antisense strand sequence are 2′-O-methyl nucleotides; and/or (iv) no more than 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the antisense strand are 2′-O-methyl nucleotides.

In some embodiments, the sense strand and/or the antisense strand can comprise one or more phosphorothioate internucleoside linkage(s). In some embodiments, the siNA can further comprise a phosphorylation blocker and/or a 5′-stabilized end cap.

In some embodiments, the sense strand can further comprise a TT sequence adjacent to the first nucleotide sequence.

In some embodiments, at least one end of the siNA can be a blunt end. In some embodiments, at least one end of the siNA can comprise an overhang, wherein the overhang comprises at least one nucleotide. In some embodiments, both ends of the siNA can comprise an overhang, wherein the overhang comprises at least one nucleotide.

In some embodiments, the sense strand can further comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more phosphorothioate internucleotide linkages. In some embodiments, the antisense strand can further comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more phosphorothioate internucleotide linkages.

In some embodiments, the sense strand and/or the antisense strand can comprise one or more modified nucleotides. In some embodiments, the modified nucleotides are independently selected from 2′-O-methyl nucleotides and 2′-fluoro nucleotides. In some embodiments, at least one 2′-fluoro nucleotide or 2′-O-methyl nucleotide is a 2′-fluoro or 2′-O-methyl nucleotide mimic of Formula (V):

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wherein R¹is a nucleobase, aryl, heteroaryl, or H, Q¹and Q²are independently S or O, R⁵is —OCD₃, —F, or —OCH₃, and R⁶and R⁷are independently H or D.

In some embodiments, the sense strand and/or antisense strand comprises at least one modified nucleotide selected from

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where R is H or alkyl (or AmNA(N-Me)) when R is alkyl);

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wherein B is a nucleobase.

In some embodiments, the siNA can further comprise a phosphorylation blocker and/or a 5′-stabilized end cap. In some embodiments, the phosphorylation blocker has the structure of Formula (IV):

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wherein R¹is a nucleobase, R⁴is —O—R³⁰or —NR³¹R³², R³⁰is C₁-C₈substituted or unsubstituted alkyl; and

R³¹and R³²together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic ring. In some embodiments, R⁴is —OCH₃or —N(CH₂CH₂)₂O. In some embodiments, the phosphorylation blocker is attached to the 5′ end of the sense strand. In some embodiments, the phosphorylation blocker is attached to the 5′ end of the sense strand via one or more linkers independently selected from a phosphodiester linker, phosphorothioate linker, and phosphorodithioate linker.

In some embodiments, the 5′-stabilized end cap is a 5′ vinylphosphonate. In some embodiments, the 5′ vinylphosphonate is selected from a 5′-(E)-vinyl phosphonate or 5′-(Z)-vinyl phosphonate. In some embodiments, the 5′-vinylphosphonate is a deuterated vinyl phosphonate. In some embodiments, the deuterated vinylphosphonate is a mono-deuterated vinylphosphonate or a di-deuterated vinylphosphonate

In some embodiments, the 5′-stabilized end cap has the structure of Formula (Ia):

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wherein R¹is a nucleobase, aryl, heteroaryl, or H; R²is

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—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_n—Z or —(C₂-C₆alkenylene)-Z and R²⁰is hydrogen, or R²and R²⁰together form a 3- to 7-membered carbocyclic ring substituted with —(CR²¹R²²)_n—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4;

Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_mCO₂R²³, —OP(S)OH(CH₂)_mCO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_mP(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴, or —NR²³SO₂R²⁵; R²¹and R²²either are independently hydrogen or C₁-C₆alkyl, or R²¹and R²²together form an oxo group; R²³is hydrogen or C₁-C₆alkyl, R²⁴is —SO₂R²⁵or —C(O)R²⁵, or R²³and R²⁴together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic ring; R²⁵is C₁-C₆alkyl; and m is 1, 2, 3, or 4. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, the 5′-stabilized end cap has the structure of Formula (Ib):

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wherein

R¹is a nucleobase, aryl, heteroaryl, or H,

R²is

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—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_n—Z, or —(C₂-C₆alkenylene)-Z and R²⁰is hydrogen; or

R²and R²⁰together form a 3- to 7-membered carbocyclic ring substituted with —(CR²¹R²²)_n—Z or —(C₂-C₆alkenylene)-Z;

n is 1, 2, 3, or 4;

Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_mCO₂R²³, —OP(S)OH(CH₂)_mCO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_mP(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴,

R²¹and R²²are independently hydrogen or C₁-C₆alkyl; R²¹and R²²together form an oxo group;

R²³is hydrogen or C₁-C₆alkyl;

R²⁴is —SO₂R²⁵or —C(O)R²⁵; or

R²³and R²⁴together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic ring;

R²⁵is C₁-C₆alkyl; and

m is 1, 2, 3, or 4.

In some embodiments, the 5′-stabilized end cap is selected from the group consisting of Formula (1) to Formula (15), Formula (9X) to Formula (12X), and Formula (9Y) to Formula (12Y):

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wherein R¹is a nucleobase, aryl, heteroaryl, or H.

In some embodiments, the 5′-stabilized end cap is selected from the group consisting of Formulas (1A)-(15A), Formulas (9B)-(12B), Formulas (9AX)-(12AX), Formulas (9AY)-(12AY), Formulas (9BX)-(12BX), and Formulas (9BY)-(12BY):

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In some embodiments, the 5′-stabilized end cap can be attached to the 5′ end of the antisense strand. In some embodiments, the 5′-stabilized end cap can be attached to the 5′ end of the antisense strand via one or more linkers independently selected from a phosphodiester linker, phosphorothioate linker, phosphoramidite (HEG) linker, triethylene glycol (TEG) linker, or phosphorodithioate linker.

In some embodiments, the sense strand consists of 21 nucleotides. In some embodiments, 2′-O-methyl nucleotides are at positions 18-21 from the 5′ end of the sense strand.

In some embodiments, the antisense strand consists of 23 nucleotides. In some embodiments, 2′-O-methyl nucleotides are at positions 18-23 from the 5′ end of the antisense strand.

In another aspect, the present disclosure provides, a siNA selected from ds-siNA-005; ds-siNA-006; ds-siNA-007; ds-siNA-008; ds-siNA-009; ds-siNA-010; ds-siNA-011; ds-siNA-012; ds-siNA-013; ds-siNA-014; ds-siNA-015; ds-siNA-016; ds-siNA-017; ds-siNA-018; ds-siNA-019; ds-siNA-020; ds-siNA-021; ds-siNA-022; ds-siNA-023; ds-siNA-024; ds-siNA-025; ds-siNA-026; ds-siNA-027; ds-siNA-028; ds-siNA-029; ds-siNA-030; ds-siNA-031; ds-siNA-032; ds-siNA-033; ds-siNA-034; ds-siNA-035; ds-siNA-036; ds-siNA-037; ds-siNA-038; ds-siNA-039; ds-siNA-040; ds-siNA-041; ds-siNA-042; ds-siNA-043; ds-siNA-044; ds-siNA-045; ds-siNA-046; ds-siNA-047; ds-siNA-048; ds-siNA-049; ds-siNA-050; ds-siNA-051; ds-siNA-052; ds-siNA-053; ds-siNA-054; ds-siNA-055; ds-siNA-056; ds-siNA-057; ds-siNA-058; ds-siNA-059; ds-siNA-060; ds-siNA-061; ds-siNA-062; ds-siNA-063; ds-siNA-064; ds-siNA-065; ds-siNA-066; ds-siNA-067; ds-siNA-068; ds-siNA-069; ds-siNA-070; ds-siNA-071; ds-siNA-072; ds-siNA-073; ds-siNA-074; ds-siNA-075; ds-siNA-076; ds-siNA-077; ds-siNA-078; ds-siNA-079; ds-siNA-080; ds-siNA-081; ds-siNA-082; ds-siNA-083; ds-siNA-084; ds-siNA-085; ds-siNA-086; ds-siNA-087; ds-siNA-088; ds-siNA-089; ds-siNA-090; ds-siNA-091; ds-siNA-092; ds-siNA-093; ds-siNA-094; ds-siNA-095; ds-siNA-096; ds-siNA-097; ds-siNA-098; ds-siNA-099; ds-siNA-100; ds-siNA-101; ds-siNA-102; ds-siNA-103; ds-siNA-104; ds-siNA-105; ds-siNA-106; ds-siNA-107; ds-siNA-108; ds-siNA-109; ds-siNA-110; ds-siNA-111; ds-siNA-112; ds-siNA-113; ds-siNA-114; ds-siNA-115; ds-siNA-116; ds-siNA-117; ds-siNA-118; ds-siNA-119; ds-siNA-120; ds-siNA-121; ds-siNA-122; ds-siNA-123; ds-siNA-124; ds-siNA-125; ds-siNA-126; ds-siNA-127; ds-siNA-128; ds-siNA-129; ds-siNA-130; ds-siNA-131; ds-siNA-132; ds-siNA-133; ds-siNA-134; ds-siNA-135; ds-siNA-136; ds-siNA-137; ds-siNA-138; ds-siNA-139; ds-siNA-140; ds-siNA-141; ds-siNA-142; ds-siNA-143; ds-siNA-144; ds-siNA-145; ds-siNA-146; ds-siNA-147; ds-siNA-148; ds-siNA-149; ds-siNA-150; ds-siNA-151; ds-siNA-152; ds-siNA-153; ds-siNA-154; ds-siNA-155; ds-siNA-156; ds-siNA-157; ds-siNA-158; ds-siNA-159; ds-siNA-160; ds-siNA-161; ds-siNA-162; ds-siNA-163; ds-siNA-164; ds-siNA-165; ds-siNA-166; ds-siNA-167; ds-siNA-168; ds-siNA-169; ds-siNA-170; ds-siNA-171; ds-siNA-172; ds-siNA-173; ds-siNA-174; ds-siNA-175; ds-siNA-176; ds-siNA-177; ds-siNA-178; ds-siNA-179; ds-siNA-180; ds-siNA-181; ds-siNA-182; ds-siNA-183; ds-siNA-184; ds-siNA-185; ds-siNA-186; ds-siNA-187; ds-siNA-188; ds-siNA-189; ds-siNA-190; ds-siNA-191; ds-siNA-192; ds-siNA-193; ds-siNA-194; ds-siNA-195; ds-siNA-196; ds-siNA-197; ds-siNA-198; ds-siNA-199; ds-siNA-200; ds-siNA-201; ds-siNA-202; ds-siNA-203; ds-siNA-204; ds-siNA-205; ds-siNA-206; ds-siNA-207; ds-siNA-208; ds-siNA-209; ds-siNA-210; ds-siNA-211; ds-siNA-212; ds-siNA-213; ds-siNA-214; ds-siNA-215; ds-siNA-216; ds-siNA-217; ds-siNA-218; ds-siNA-219; ds-siNA-220; ds-siNA-221; and ds-siNA-222.

In some embodiments, the siNA is selected from ds-siNA-196 (sense and antisense respectively comprising SEQ ID NOs: 4578 and 4800), ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs: 4579 and 4801), ds-siNA-198 (sense and antisense respectively comprising SEQ ID NOs: 4580 and 4802), ds-siNA-199 (sense and antisense respectively comprising SEQ ID NOs: 4581 and 4803), ds-siNA-217 (sense and antisense respectively comprising SEQ ID NOs: 4599 and 4821), ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisense respectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisense respectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs: 4603 and 4825), and ds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs: 4604 and 4826).

In some embodiments, the siNA is selected from, ds-siNA-217 (sense and antisense respectively comprising SEQ ID NOs: 4599 and 4821), ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisense respectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisense respectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs: 4603 and 4825), and ds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs: 4604 and 4826).

In another aspect, the present disclosure provides pharmaceutical compositions comprising at least one siNA according to any one of the embodiments described herein and a pharmaceutically acceptable carrier or diluent.

In some embodiments, the pharmaceutical composition can comprise two or more siNA according to any of the embodiments described herein.

In another aspect, the present disclosure provides methods for treating a disease in a subject in need thereof, comprising administering the subject a pharmaceutical composition according to any of the embodiments described herein.

In another aspect, the present disclosure provides uses of a ds-siRNA according to any of the embodiments described herein in the manufacture of a medicament for treating a disease.

In another aspect, the present disclosure provides methods for treating a disease in a subject in need thereof, comprising administering the subject a siNA according to any of the embodiments described herein. In some embodiments, wherein the disease is a viral disease. In some embodiments, the viral disease is caused by an RNA virus. In some embodiments, the RNA virus is a single-stranded RNA virus (ssRNA virus). In some embodiments, the ssRNA virus is a positive-sense single-stranded RNA virus ((+)ssRNA virus). In some embodiments, the (+)ssRNA virus is a coronavirus. In some embodiments, the coronavirus is a β-coronavirus. In some embodiments, the β-coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also known by the provisional name 2019 novel coronavirus, or 2019-nCoV), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV, also known by the provisional name 2012 novel coronavirus, or 2012-nCoV), or severe acute respiratory syndrome-related coronavirus (SARS-CoV, also known as SARS-CoV-1). In some embodiments, the β-coronavirus is SARS-CoV-2. In some embodiments, the (3-coronavirus is SARS-CoV. In some embodiments, the β-coronavirus is MERS-CoV. In some embodiments, the β-coronavirus is hCoV-OC43.

In some embodiments, the disease is a respiratory disease. In some embodiments, the respiratory disease is viral pneumonia. In some embodiments, the respiratory disease is an acute respiratory infection. In some embodiments, the respiratory disease is a cold. In some embodiments, the respiratory disease is severe acute respiratory syndrome (SARS). In some embodiments, the respiratory disease is Middle East respiratory syndrome (MERS). In some embodiments, the disease is coronavirus disease 2019 (COVID-19). In some embodiments, the respiratory disease causes one or more symptoms selected from coughing, sore throat, runny nose, sneezing, headache, fever, shortness of breath, myalgia, abdominal pain, fatigue, difficulty breathing, persistent chest pain or pressure, difficulty waking, loss of smell and taste, muscle or joint pain, chills, nausea or vomiting, nasal congestion, diarrhea, haemoptysis, conjunctival congestion, sputum production, chest tightness, and palpitations. In some embodiments, the respiratory disease can cause complications selected from sinusitis, otitis media, pneumonia, acute respiratory distress syndrome, disseminated intravascular coagulation, pericarditis, and kidney failure. In some embodiments, the respiratory disease is idiopathic.

In another aspect, the present disclosure provides methods of treating a β-coronavirus-caused disease in a subject in need thereof, comprising administering the subject a siNA comprising a sense strand that is 15 to 30 nucleotides in length, wherein the sense strand is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequence within a region of either two, three, or four of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, the sense strand is identical to an RNA sequence corresponding to a region of each of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, the sense strand is selected from the group consisting of sequences corresponding to SEQ ID NOs: 1-1203 and 2411-3392.

In another aspect, the present disclosure provides methods of treating a β-coronavirus-caused disease in a subject in need thereof, comprising administering the subject a siNA comprising antisense strand that is 15 to 30 nucleotides in length, wherein the antisense strand is complementary to a sequence within a region of either two, three, or four of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, the second nucleotide sequence is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to an RNA sequence corresponding to a region of each of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, the antisense strand comprises a sequence corresponding to one of SEQ ID NOs: 1204-2406 and 3393-4374.

In another aspect, the present disclosure provides methods of treating a β-coronavirus-caused disease in a subject in need thereof, comprising administering the subject a siNA comprising a sense strand that is 15 to 30 nucleotides in length, wherein the sense strand is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to a sequence within a region of either two, three, or four of the genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and severe acute respiratory syndrome-related coronavirus (SARS-CoV). In some embodiments, the sense strand is identical to a sequence within a region of each of the genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and severe acute respiratory syndrome-related coronavirus (SARS-CoV).

In another aspect, the present disclosure provides methods of treating a β-coronavirus-caused disease in a subject in need thereof, comprising administering the subject a siNA comprising an antisense strand that is 15 to 30 nucleotides in length, wherein the antisense strand is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to a sequence within a region of either two, three, or four of the genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and severe acute respiratory syndrome-related coronavirus (SARS-CoV). In some embodiments, the second nucleotide sequence is complementary to a sequence within a region of each of the genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and severe acute respiratory syndrome-related coronavirus (SARS-CoV).

A method of treating a β-coronavirus-caused disease in a subject in need thereof, comprising administering the subject a siNA selected from ds-siNA-005; ds-siNA-006; ds-siNA-007; ds-siNA-008; ds-siNA-009; ds-siNA-010; ds-siNA-011; ds-siNA-012; ds-siNA-013; ds-siNA-014; ds-siNA-015; ds-siNA-016; ds-siNA-017; ds-siNA-018; ds-siNA-019; ds-siNA-020; ds-siNA-021; ds-siNA-022; ds-siNA-023; ds-siNA-024; ds-siNA-025; ds-siNA-026; ds-siNA-027; ds-siNA-028; ds-siNA-029; ds-siNA-030; ds-siNA-031; ds-siNA-032; ds-siNA-033; ds-siNA-034; ds-siNA-035; ds-siNA-036; ds-siNA-037; ds-siNA-038; ds-siNA-039; ds-siNA-040; ds-siNA-041; ds-siNA-042; ds-siNA-043; ds-siNA-044; ds-siNA-045; ds-siNA-046; ds-siNA-047; ds-siNA-048; ds-siNA-049; ds-siNA-050; ds-siNA-051; ds-siNA-052; ds-siNA-053; ds-siNA-054; ds-siNA-055; ds-siNA-056; ds-siNA-057; ds-siNA-058; ds-siNA-059; ds-siNA-060; ds-siNA-061; ds-siNA-062; ds-siNA-063; ds-siNA-064; ds-siNA-065; ds-siNA-066; ds-siNA-067; ds-siNA-068; ds-siNA-069; ds-siNA-070; ds-siNA-071; ds-siNA-072; ds-siNA-073; ds-siNA-074; ds-siNA-075; ds-siNA-076; ds-siNA-077; ds-siNA-078; ds-siNA-079; ds-siNA-080; ds-siNA-081; ds-siNA-082; ds-siNA-083; ds-siNA-084; ds-siNA-085; ds-siNA-086; ds-siNA-087; ds-siNA-088; ds-siNA-089; ds-siNA-090; ds-siNA-091; ds-siNA-092; ds-siNA-093; ds-siNA-094; ds-siNA-095; ds-siNA-096; ds-siNA-097; ds-siNA-098; ds-siNA-099; ds-siNA-100; ds-siNA-101; ds-siNA-102; ds-siNA-103; ds-siNA-104; ds-siNA-105; ds-siNA-106; ds-siNA-107; ds-siNA-108; ds-siNA-109; ds-siNA-110; ds-siNA-111; ds-siNA-112; ds-siNA-113; ds-siNA-114; ds-siNA-115; ds-siNA-116; ds-siNA-117; ds-siNA-118; ds-siNA-119; ds-siNA-120; ds-siNA-121; ds-siNA-122; ds-siNA-123; ds-siNA-124; ds-siNA-125; ds-siNA-126; ds-siNA-127; ds-siNA-128; ds-siNA-129; ds-siNA-130; ds-siNA-131; ds-siNA-132; ds-siNA-133; ds-siNA-134; ds-siNA-135; ds-siNA-136; ds-siNA-137; ds-siNA-138; ds-siNA-139; ds-siNA-140; ds-siNA-141; ds-siNA-142; ds-siNA-143; ds-siNA-144; ds-siNA-145; ds-siNA-146; ds-siNA-147; ds-siNA-148; ds-siNA-149; ds-siNA-150; ds-siNA-151; ds-siNA-152; ds-siNA-153; ds-siNA-154; ds-siNA-155; ds-siNA-156; ds-siNA-157; ds-siNA-158; ds-siNA-159; ds-siNA-160; ds-siNA-161; ds-siNA-162; ds-siNA-163; ds-siNA-164; ds-siNA-165; ds-siNA-166; ds-siNA-167; ds-siNA-168; ds-siNA-169; ds-siNA-170; ds-siNA-171; ds-siNA-172; ds-siNA-173; ds-siNA-174; ds-siNA-175; ds-siNA-176; ds-siNA-177; ds-siNA-178; ds-siNA-179; ds-siNA-180; ds-siNA-181; ds-siNA-182; ds-siNA-183; ds-siNA-184; ds-siNA-185; ds-siNA-186; ds-siNA-187; ds-siNA-188; ds-siNA-189; ds-siNA-190; ds-siNA-191; ds-siNA-192; ds-siNA-193; ds-siNA-194; ds-siNA-195; ds-siNA-196; ds-siNA-197; ds-siNA-198; ds-siNA-199; ds-siNA-200; ds-siNA-201; ds-siNA-202; ds-siNA-203; ds-siNA-204; ds-siNA-205; ds-siNA-206; ds-siNA-207; ds-siNA-208; ds-siNA-209; ds-siNA-210; ds-siNA-211; ds-siNA-212; ds-siNA-213; ds-siNA-214; ds-siNA-215; ds-siNA-216; ds-siNA-217; ds-siNA-218; ds-siNA-219; ds-siNA-220; ds-siNA-221; and ds-siNA-222. In some embodiments, the siNA is selected from ds-siNA-196 (sense and antisense respectively comprising SEQ ID NOs: 4578 and 4800), ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs: 4579 and 4801), ds-siNA-198 (sense and antisense respectively comprising SEQ ID NOs: 4580 and 4802), ds-siNA-199 (sense and antisense respectively comprising SEQ ID NOs: 4581 and 4803), ds-siNA-217 (sense and antisense respectively comprising SEQ ID NOs: 4599 and 4821), ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisense respectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisense respectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs: 4603 and 4825), and ds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs: 4604 and 4826). In some embodiments, the siNA is selected from ds-siNA-196 (sense and antisense respectively comprising SEQ ID NOs: 4578 and 4800), ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs: 4579 and 4801), ds-siNA-198 (sense and antisense respectively comprising SEQ ID NOs: 4580 and 4802), and ds-siNA-199 (sense and antisense respectively comprising SEQ ID NOs: 4581 and 4803). In some embodiments, the siNA is selected from, ds-siNA-217 (sense and antisense respectively comprising SEQ ID NOs: 4599 and 4821), ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisense respectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisense respectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs: 4603 and 4825), and ds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs: 4604 and 4826). In some embodiments, the (3-coronavirus can be SARS-CoV-2. In some embodiments, the β-coronavirus-caused disease can be COVID-19.

In some embodiments of the disclosed methods and uses, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human primate. In some embodiments, the subject is a cat. In some embodiments, the subject is a camel.

In some embodiments of the disclosed methods and uses, the siNA is administered intravenously, subcutaneously, or via inhalation.

In some embodiments of the disclosed methods and uses, the subject has been treated with one or more additional coronavirus treatment agents. In some embodiments of the disclosed methods, the subject is concurrently treated with one or more additional coronavirus treatment agents.

The foregoing general description and following detailed description are exemplary and explanatory and are intended to provide further explanation of the disclosure as claimed. Other objects, advantages, and novel features will be readily apparent to those skilled in the art from the following brief description of the drawings and detailed description of the disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 (FIG. 1) shows the coronaviridae family and its four genera (top panel) and the full length genome of NCBI 407 (bottom panel), which encodes 28 proteins across multiple open reading frames (ORF s).

FIG. 2 (FIG. 2) shows the percent identity between multiple coronavirus, including sudden acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus OC43 (top panel), and an alignment of the highly similar region of the genomes encodings non-structural protein 8 (nsp8) to non-structural protein (nsp15) (bottom panel).

FIG. 3 (FIG. 3) shows details of nsp8-nsp15.

FIG. 4 (FIG. 4) shows an exemplary siNA molecule.

FIG. 5 (FIG. 5) shows an exemplary siNA molecule.

FIGS. 6A-6I (FIGS. 6A-6I) show exemplary double-stranded siNA molecules.

DETAILED DESCRIPTION

Disclosed herein are short interfering nucleic acid (siNA) molecules. In some embodiments, the siNA is a double-stranded siNA (ds-siNA). In some embodiments, the ds-siNA comprises a sense strand and an antisense strand. In some embodiments, the ds-siNA comprises (a) a sense strand comprising a first nucleotide sequence, wherein the first nucleotide sequence is 15 to 30 nucleotides in length; and (b) an antisense strand comprising a second nucleotide sequence, wherein the second nucleotide sequence is 15 to 30 nucleotides in length and comprises a nucleotide sequence that is the reverse complement of the first nucleotide sequence.

Further disclosed herein are pharmaceutical compositions comprising the ds-siNA according to any one of the embodiments described herein and a pharmaceutically acceptable carrier or diluent. In some embodiments the disclosed compositions may comprise two or more ds-siNA according to any of the embodiments described herein.

Further disclosed herein is a method for treating a disease in a subject in need thereof, comprising administering the subject one or more siNA or pharmaceutical compositions of any of the embodiments described herein. In some embodiments, the disease is a viral infection, such as a coronavirus infection (e.g., COVID-19).

Further disclosed herein is the use of one or more ds-siRNA according to any of the embodiments described herein in the manufacture of a medicament for treating a disease, such as a viral infection or, more specifically, a coronavirus infection (e.g., COVID-19).

Further disclosed herein is a method for treating a disease in a subject in need thereof, comprising administering the subject one or more ds-siNA or pharmaceutical compositions of any of the embodiments described herein.

Further disclosed herein is a method of treating a β-coronavirus-caused disease (e.g., COVID-19) in a subject in need thereof, comprising administering the subject one or more ds-siNA according to any of the embodiments described herein.

As described in more detail below, the disclose siNA molecules may comprise modified nucleotides. The modified nucleotides may be selected from 2′-O-methyl nucleotides and 2′-fluoro nucleotides. The siNA molecules described herein may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more phosphorothioate internucleoside linkages. The siNA molecules described herein may comprise at least one phosphorylation blocker. The siNA molecules described herein may comprise a 5′-stabilized end cap. The siNA molecules described herein may comprise one or more blunt ends. The siNA molecules described herein may comprise one or more overhangs.

Further, the disclosed siNA molecules may comprise (a) a phosphorylation blocker; and (b) a siNA. The siNA may comprise at least 5 nucleotides. The nucleotides may be modified nucleotides, non-modified nucleotides, or any combination thereof. The nucleotides may be ribonucleotides, deoxyribonucleotides, or any combination thereof. The siNA may be single-stranded. Alternatively, the siNA is double-stranded. The double-stranded siNA may comprise one or more blunt ends. The double-stranded siNA may comprise one or more overhangs. The double-stranded siNA may comprise a blunt end and an overhang.

Further, the disclosed siNA molecules may comprise (a) a conjugated moiety; and (b) a siNA. The siNA may comprise at least 5 nucleotides. The nucleotides may be modified nucleotides, non-modified nucleotides, or any combination thereof. The nucleotides may be ribonucleotides, deoxyribonucleotides, or any combination thereof. The siNA may be single-stranded. Alternatively, the siNA is double-stranded. The double-stranded siNA may comprise one or more blunt ends. The double-stranded siNA may comprise one or more overhangs. The double-stranded siNA may comprise a blunt end and an overhang.

Further, the disclosed siNA molecules may comprise (a) a 5′-stabilized end cap; and (b) a siNA. The siNA may comprise at least 5 nucleotides. The nucleotides may be modified nucleotides, non-modified nucleotides, or any combination thereof. The nucleotides may be ribonucleotides, deoxyribonucleotides, or any combination thereof. The siNA may be single-stranded. Alternatively, the siNA is double-stranded. The double-stranded siNA may comprise one or more blunt ends. The double-stranded siNA may comprise one or more overhangs. The double-stranded siNA may comprise a blunt end and an overhang.

Further, the disclosed siNA molecules may comprise (a) at least one phosphorylation blocker, conjugated moiety, or 5′-stabilized end cap; and (b) a siNA. The siNA may comprise at least 5 nucleotides. The nucleotides may be modified nucleotides, non-modified nucleotides, or any combination thereof. The nucleotides may be ribonucleotides, deoxyribonucleotides, or any combination thereof. The siNA may be single-stranded. Alternatively, the siNA is double-stranded. The double-stranded siNA may comprise one or more blunt ends. The double-stranded siNA may comprise one or more overhangs. The double-stranded siNA may comprise a blunt end and an overhang.

Exemplary siNA, which may be used to treat and/or prevent coronavirus infections (e.g., COVID-19) are also described herein.

Definitions

It is to be understood that methods are not limited to the particular embodiments described, and as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. The scope of the present technology will be limited only by the appended claims.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are now described.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

As used in the specification and claims, the singular form “a,” “an” and “the” include singular and plural references unless the context clearly dictates otherwise.

As used herein, the term “comprising” is intended to mean that the compositions and methods include the recited elements, but not excluding others. “Consisting essentially of” when used to define compositions and methods, shall mean excluding other elements of any essential significance to the composition or method. “Consisting of” shall mean excluding more than trace elements of other ingredients for claimed compositions and substantial method steps. Embodiments defined by each of these transition terms are within the scope of this disclosure. Accordingly, it is intended that the methods and compositions can include additional steps and components (comprising) or alternatively including steps and compositions of no significance (consisting essentially of) or alternatively, intending only the stated method steps or compositions (consisting of).

As used herein, “about” means plus or minus 10% as well as the specified number. For example, “about 10” should be understood as both “10” and “9-11.”

As used herein, “optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

The terms “individual,” “subject,” and “patient” are used interchangeably herein, and refer to any individual mammal, e.g., bovine, canine, feline, equine, simian, porcine, camelid, bat, or human, being treated according to the disclosed methods or uses. In preferred embodiments, the subject is a human.

As used herein, the phrases “effective amount,” “therapeutically effective amount,” and “therapeutic level” mean the siNA dosage or concentration in a subject that provides the specific pharmacological effect for which the siNA is administered in a subject in need of such treatment, i.e. to treat or prevent a coronavirus infection (e.g., MERS, SARS, or COVID-19). It is emphasized that a therapeutically effective amount or therapeutic level of an siNA will not always be effective in treating the infections described herein, even though such dosage is deemed to be a therapeutically effective amount by those of skill in the art. For convenience only, exemplary dosages, drug delivery amounts, therapeutically effective amounts, and therapeutic levels are provided below. Those skilled in the art can adjust such amounts in accordance with standard practices as needed to treat a specific subject and/or condition. The therapeutically effective amount may vary based on the route of administration and dosage form, the age and weight of the subject, and/or the subject's condition, including the type and severity of the coronavirus infection.

The terms “treatment” or “treating” as used herein with reference to a coronavirus infections refer to reducing or eliminating viral load and/or improving or ameliorating one or more symptoms of an infection such as cough, shortness of breath, body aches, chills, and/or fever.

The terms “prevent” or “preventing” as used herein with reference to a coronavirus infections refer to precluding an infection from developing in a subject exposed to a coronavirus and/or avoiding the development of one or more symptoms of an infection such as cough, shortness of breath, body aches, chills, and/or fever. “Prevention” may occur when the viral load is never allowed to exceed beyond a threshold level at which point the subject begins to feel sick or exhibit symptoms. “Prevention” may also, in some embodiments, refer to the prevention of a subsequent infection once an initial infection has been treated or cured.

As used herein, the term “pharmaceutical composition” refers to the combination of an active agent with a carrier, inert or active, making the composition especially suitable for diagnostic or therapeutic use in vivo or ex vivo.

As used herein, the term “pharmaceutically acceptable carrier” refers to any of the standard pharmaceutical carriers, such as a phosphate buffered saline solution, water, emulsions (e.g., such as an oil/water or water/oil emulsions), and various types of wetting agents. The compositions also can include stabilizers and preservatives. For examples of carriers, stabilizers and adjuvants, see, for example, Martin, Remington's Pharmaceutical Sciences, 15th Ed., Mack Publ. Co., Easton, Pa. [1975].

The phrases “parenteral administration” and “administered parenterally” as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

The phrases “systemic administration,” “administered systemically,” “peripheral administration” and “administered peripherally” as used herein mean the administration of a compound, drug or other material other than directly into the central nervous system, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration.

As used herein, the term “nucleobase” refers to a nitrogen-containing biological compound that forms a nucleoside. Examples of nucleobases include, but are not limited to, thymine, uracil, adenine, cytosine, guanine, aryl, heteroaryl, and an analogue or derivative thereof.

The target gene may be any gene in a cell or virus. Here, “target gene” and “target sequence” are used synonymously.

For the purposes of the present disclosure, a DNA sequence that replaces all the U residues of an RNA sequence with T residues is “identical” to the RNA sequence, and vice versa. Accordingly, a sequence that is “identical to an RNA corresponding to” a DNA sequence constitutes the DNA sequence with all T replaced by U. The presence of modified nucleotides or 2′-deoxynucleotides in a sequence does not make a sequence not “identical to an RNA” but rather a modified RNA.

As used herein, “modified nucleotide” includes any nucleic acid or nucleic acid analogue residue that contains a modification or substitution in the chemical structure of an unmodified nucleotide base, sugar (including, but not limited to, 2′-substitution), or phosphate (including, but not limited to, alternate internucleotide linkers, such as phosphorothioates or the substitution of bridging oxygens in phosphate linkers with bridging sulfurs), or a combination thereof. Non-limiting examples of modified nucleotides are shown herein.

As used herein, the term “d2vd3 nucleotide” refers to a nucleotide comprising a 5′-stabilized end cap of Formula (10):

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Throughout the description, where compositions are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are compositions of the present disclosure that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present disclosure that consist essentially of, or consist of, the recited processing steps.

As a general matter, compositions specifying a percentage are by weight unless otherwise specified. Further, if a variable is not accompanied by a definition, then the previous definition of the variable controls.

Coronaviruses and Coronavirus Infections

The siNA molecules and compositions described herein may be administered to a subject to treat a disease. Further disclosed herein are uses of any of the siNA molecules or compositions disclosed herein in the manufacture of a medicament for treating a disease.

In some embodiments of the disclosed method and uses, the disease being treated is a viral disease. In some embodiments, the viral disease is caused by an RNA virus. In some embodiments, the RNA virus is a single-stranded RNA virus (ssRNA virus). In some embodiments, the ssRNA virus is a positive-sense single-stranded RNA virus ((+)ssRNA virus). In some embodiments, the (+)ssRNA virus is a coronavirus.

Coronaviruses are a family of viruses (i.e., the coronaviridae family) that cause respiratory infections in mammals and that comprise a genome that is roughly 30 kilobases in length. The coronaviridae family is divided into four genera and the genome encodes 28 proteins across multiple open reading frames, including 16 non-structural proteins (nsp) that are post-translationally cleaved from a polyprotein (see FIG. 1).

The coronaviridae family includes both α-coronaviruses or β-coronaviruses, which both mainly infect bats, but can also infect other mammals like humans, camels, and rabbits. β-coronaviruses have, to date, been of greater clinical importance, having caused epidemics including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19. Other disease-causing β-coronaviruses include OC44, and HKU1. Non-limiting examples of disease-causing α-coronaviruses include, but are not limited to, 229E and NL63.

In some embodiments, the coronavirus is a β-coronaviruses. In some embodiments, the β-coronaviruses is selected from the group consisting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also known by the provisional name 2019 novel coronavirus, or 2019-nCoV), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV, also known by the provisional name 2012 novel coronavirus, or 2012-nCoV), and severe acute respiratory syndrome-related coronavirus (SARS-CoV, also known as SARS-CoV-1). In some embodiments, the β-coronaviruses is SARS-CoV-2, the causative agent of COVID-19.

As shown in FIGS. 2 and 3, several disease-causing coronaviruses share a high degree of homology in the regions of the genome encoding non-structural proteins (nsp), and more specifically, in the region encoding nsp8-nsp15. Indeed, there is roughly 65% identity across the roughly 7 kB sequence of β-coronaviruses from about nucleotide 12900 to about nucleotide 19900 of 2019-nCoV, and some subsections of the genomic span of nsp8 to nsp15 may comprise 95% or more identity. All of the genes in this region encode non-structural proteins associated with replication. Accordingly, this segment of the genome is suitable for targeting with an siNA that can provide a broad spectrum treatment for multiple different types of coronavirus, such as MERS-CoV, SARS-CoV-1, and SARS-CoV-2.

Without wishing to be bound by theory, upon entry into a cell, any of the ds-siNA molecules disclosed herein may interact with proteins in the cell to form a RNA-Induced Silencing Complex (RISC). Once the ds-siNA is part of the RISC, the ds-siNA may be unwound to form a single-stranded siNA (ss-siNA). The ss-siNA may comprise the antisense strand of the ds-siNA. The antisense strand may bind to a complementary messenger RNA (mRNA), which results in silencing of the gene that encodes the mRNA.

In some embodiments, the target gene is a viral gene. In some embodiments, the viral gene is from an RNA virus. In some embodiments, the RNA virus is a single-stranded RNA virus (ssRNA virus). In some embodiments, the ssRNA virus is a positive-sense single-stranded RNA virus ((+)ssRNA virus). In some embodiments, the (+)ssRNA virus is a coronavirus. In some embodiments, the coronavirus is a β-coronavirus. In some embodiments, the β-coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also known by the provisional name 2019 novel coronavirus, or 2019-nCoV), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV, also known by the provisional name 2012 novel coronavirus, or 2012-nCoV), severe acute respiratory syndrome-related coronavirus (SARS-CoV, also known as SARS-CoV-1). In some embodiments, the β-coronavirus is SARS-CoV-2.

In some embodiments, the target gene is selected from genome of SARS-CoV-2. In some embodiments, SARS-CoV-2 has a genome sequence shown in the nucleotide sequence of SEQ ID NO: 2407, which corresponds to the nucleotide sequence of GenBank Accession No. NC_045512.2, which is incorporated by reference in its entirety.

In some embodiments, the target gene is selected from genome of SARS-CoV. In some embodiments, SARS-CoV has a genome sequence shown in the nucleotide sequence of SEQ ID NO: 2408, which corresponds to the nucleotide sequence of GenBank Accession No. NC_004718.3, which is incorporated by reference in its entirety.

In some embodiments, the target gene is selected from the genome of MERS-CoV. In some embodiments, MERS-CoV has a genome sequence shown in the nucleotide sequence of SEQ ID NO: 2409, which corresponds to the nucleotide sequence of GenBank Accession No. NC_019843.3, which is incorporated by reference in its entirety.

In some embodiments, the target gene is selected from the genome of hCoV-OC43. In some embodiments, hCoV-OC43 has a genome sequence shown in the nucleotide sequence of SEQ ID NO: 2410, which corresponds to the nucleotide sequence of GenBank Accession No. NC_006213.1, which is incorporated by reference in its entirety.

Short Interfering Nucleic Acid (siNA) Molecules

As indicated above, the present disclosure provides siNA molecules comprising modified nucleotides. Any of the siNA molecules described herein may be double-stranded siNA (ds-siNA) molecules. The terms “siNA molecules” and “ds-siNA molecules” may be used interchangeably. In some embodiments, the ds-siNA molecules comprise a sense strand and an antisense strand.

The disclosed siNA molecules may comprise (a) at least one phosphorylation blocker, conjugated moiety, or 5′-stabilized end cap; and (b) a short interfering nucleic acid (siNA). In some embodiments, the phosphorylation blocker is a phosphorylation blocker disclosed herein. In some embodiments, the 5′-stabilized end cap is a 5′-stabilized end cap disclosed herein. The siNA may comprise any of the first nucleotide, second nucleotide, sense strand, or antisense strand sequences disclosed herein. The siNA may comprise 5 to 100, 5 to 90, 10 to 100, 10 to 90, 10 to 80, 10 to 70, 10 to 60, 10 to 50, 10 to 30, 10 to 25, 15 to 100, 15 to 90, 15 to 80, 15 to 70, 15 to 60, 15 to 50, 15 to 30, or 15 to 25 nucleotides. The siNA may comprise at least 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 nucleotides. The siNA may comprise less than or equal to 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, or 19 nucleotides. The nucleotides may be modified nucleotides. The siNA may be single stranded. The siNA may be double stranded. The siNA may comprise (a) a sense strand comprising 15 to 30, 15 to 25, 15 to 24, 15 to 23, 15 to 22, 15 to 21, 17 to 30, 17 to 25, 17 to 24, 17 to 23, 17 to 22, 17 to 21, 18 to 30, 18 to 25, 18 to 24, 18 to 23, 18 to 22, 18 to 21, 19 to 30, 19 to 25, 19 to 24, 19 to 23, 19 to 22, 19 to 21, 20 to 25, 20 to 24, 20 to 23, 21 to 25, 21 to 24, or 21 to 23 nucleotides; and (b) an antisense strand comprising 15 to 30, 15 to 25, 15 to 24, 15 to 23, 15 to 22, 15 to 21, 17 to 30, 17 to 25, 17 to 24, 17 to 23, 17 to 22, 17 to 21, 18 to 30, 18 to 25, 18 to 24, 18 to 23, 18 to 22, 18 to 21, 19 to 30, 19 to 25, 19 to 24, 19 to 23, 19 to 22, 19 to 21, 20 to 25, 20 to 24, 20 to 23, 21 to 25, 21 to 24, or 21 to 23 nucleotides. The siNA may comprise (a) a sense strand comprising about 15, 16, 17, 18, 19, 20, 21, 22, or 23 nucleotides; and (b) an antisense strand comprising about 15, 16, 17, 18, 19, 20, 21, 22, or 23 nucleotides. The siNA may comprise (a) a sense strand comprising about 19 nucleotides; and (b) an antisense strand comprising about 21 nucleotides. The siNA may comprise (a) a sense strand comprising about 21 nucleotides; and (b) an antisense strand comprising about 23 nucleotides.

In some embodiments, any of the siNA molecules disclosed herein further comprise one or more linkers independently selected from a phosphodiester (PO) linker, phosphorothioate (PS) linker, phosphorodithioate linker, and PS-mimic linker. In some embodiments, the PS-mimic linker is a sulfur linker. In some embodiments, the linkers are internucleotide linkers. Alternatively, or additionally, the linkers connect a nucleotide of the siNA molecule to at least one phosphorylation blocker, conjugated moiety, or 5′-stabilized end cap. In some embodiments, the linkers connect a conjugated moiety to a phosphorylation blocker or 5′-stabilized end cap.

Table 1 details sequences of the present disclosure useful for sense and antisense strands, disclosed in SEQ ID NOs: 1-2406 and 3393-4374. Table 2 details representative genome sequences of four pathogenic β-coronaviruses, disclosed in SEQ ID NOs: 2407-2410. It is understood that RNA sequences corresponding to these sequences constitute identical sequences with all T replaced with U.

In some embodiments, the target gene a sequence 15 to 30, 15 to 25, 15 to 23, 17 to 23, 19 to 23, or 19 to 21 nucleotides in length, and preferably 19 or 21 nucleotides in length, within a region of either two, three, or four of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, the first nucleotide sequence is identical to an RNA sequence corresponding to a region of each of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, the target gene a sequence 15 to 30, 15 to 25, 15 to 23, 17 to 23, 19 to 23, or 19 to 21 nucleotides in length, and preferably 19 or 21 nucleotides in length, within a region of either two, three, or four of the genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and severe acute respiratory syndrome-related coronavirus (SARS-CoV). In some embodiments, the first nucleotide sequence is identical to an RNA sequence corresponding to a region of each of two, three, or four of the genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (hCoV-OC43), Middle East respiratory syndrome-related coronavirus (MERS-CoV), and severe acute respiratory syndrome-related coronavirus (SARS-CoV). In some embodiments, the first nucleotide sequence is identical to the target gene. In some embodiments, the second nucleotide sequence is complementary to the target gene.

In some embodiments, the second nucleotide sequence is complementary to a sequence within a region of either two, three, or four of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, the second nucleotide sequence is complementary to an RNA sequence corresponding to a region of each of SEQ ID NOs: 2407, 2408, 2409, and 2410. In some embodiments, the second nucleotide sequence comprises a sequence corresponding to one of SEQ ID NOs: 1204-2406 and 3393-4374.

In some embodiments, the second nucleotide is complementary to a nucleotide region within SEQ ID NO: 2407, 2408, 2409, or 2410. In some embodiments, the second nucleotide sequence is complementary to 15 to 30, 15 to 25, 15 to 23, 15 to 22, 15 to 21, 17 to 25, 17 to 23, 17 to 22, 17 to 21, or 19 to 21 nucleotides, and preferably 19 to 21 nucleotides, and more preferably 19 or 21 nucleotides, within positions 190-216, 233-279, 288-324, 455-477, 626-651, 704-723, 3352-3378, 5384-5403, 6406-6483, 7532-7551, 9588-9606, 10484-10509, 11609-11630, 11834-11853, 12023-12045, 12212-12234, 12401-12420, 12839-12867, 12885-12924, 12966-12990, 13151-13176, 13363-13386, 13388-13416, 13458-13416, 13458-13520, 13762-13790, 14290-14312, 14404-14429, 14500-14531, 14623-14642, 14650-14687, 14698-14717, 14722-14748, 14750-14777, 14821-14846, 14854-14873, 14875-14903, 14962-14990, 14992-15020, 15055-15140, 15172-15200, 15310-15332, 15346-15367, 15496-15518, 15622-15644, 15838-15869, 15886-15905, 15985-16010, 16057-16079, 16186-16205, 16430-16448, 16822-16865, 16954-16976, 17008-17042, 17080-17111, 17137-17156, 17269-17289, 17530-17549, 17563-17582, 17680-17699, 17746-17765, 17857-17876, 17956-17975, 18100-18122, 18196-18218, 19618-19639, 19783-19802, 19831-19850, 20107-20130, 20776-20795, 21502-21524, 24302-24325, 24446-24465, 24620-24651, 24662-24684, 25034-25057, 25104-25128, 25364-25387, 25502-25530, 26191-26227, 26232-26267, 26269-26330, 26332-26394, 26450-26481, 26574-26600, 27003-27064, 27093-27111, 27183-27212, 27382-27407, 27511-27533, 27771-27818, 28270-28296, 28397-28434, 28513-28546, 28673-28692, 28706-28726, 28744-28794, 28799-28827, 28946-28972, 28976-29034, 29144-29172, 29174-29196, 29228-29259, 29285-29305, 29342-29394, 29444-29463, 29543-29566, 29598-29630, 29652-29687, 29689-29731, 29733-29757, or 29770-29828 of SEQ ID NO: 2407. In some embodiments, the second nucleotide sequence is complementary to any one of SEQ ID NOs: 1-1203 and 2411-3392. In some embodiments, the second nucleotide sequence is identical to an RNA corresponding to any one of SEQ ID NOs: 1204-2406 and 3393-4374.

In some embodiments, the first nucleotide sequence is identical to a nucleotide region within SEQ ID NOs: 2407, 2408, 2409, or 2410, with the exception that the thymines (Ts) in SEQ ID NOs: 2407, 2408, 2409, or 2410 are replaced with uracil (U). In some embodiments, the first nucleotide sequence is identical to 15 to 30, 15 to 25, 15 to 23, 15 to 22, 15 to 21, 17 to 25, 17 to 23, 17 to 22, 17 to 21, or 19 to 21 nucleotides, and preferably 19 to 21 nucleotides, and more preferably 19 or 21 nucleotides, within positions 190-216, 233-279, 288-324, 455-477, 626-651, 704-723, 3352-3378, 5384-5403, 6406-6483, 7532-7551, 9588-9606, 10484-10509, 11609-11630, 11834-11853, 12023-12045, 12212-12234, 12401-12420, 12839-12867, 12885-12924, 12966-12990, 13151-13176, 13363-13386, 13388-13416, 13458-13416, 13458-13520, 13762-13790, 14290-14312, 14404-14429, 14500-14531, 14623-14642, 14650-14687, 14698-14717, 14722-14748, 14750-14777, 14821-14846, 14854-14873, 14875-14903, 14962-14990, 14992-15020, 15055-15140, 15172-15200, 15310-15332, 15346-15367, 15496-15518, 15622-15644, 15838-15869, 15886-15905, 15985-16010, 16057-16079, 16186-16205, 16430-16448, 16822-16865, 16954-16976, 17008-17042, 17080-17111, 17137-17156, 17269-17289, 17530-17549, 17563-17582, 17680-17699, 17746-17765, 17857-17876, 17956-17975, 18100-18122, 18196-18218, 19618-19639, 19783-19802, 19831-19850, 20107-20130, 20776-20795, 21502-21524, 24302-24325, 24446-24465, 24620-24651, 24662-24684, 25034-25057, 25104-25128, 25364-25387, 25502-25530, 26191-26227, 26232-26267, 26269-26330, 26332-26394, 26450-26481, 26574-26600, 27003-27064, 27093-27111, 27183-27212, 27382-27407, 27511-27533, 27771-27818, 28270-28296, 28397-28434, 28513-28546, 28673-28692, 28706-28726, 28744-28794, 28799-28827, 28946-28972, 28976-29034, 29144-29172, 29174-29196, 29228-29259, 29285-29305, 29342-29394, 29444-29463, 29543-29566, 29598-29630, 29652-29687, 29689-29731, 29733-29757, or 29770-29828 of SEQ ID NO: 2407. In some embodiments, the first nucleotide sequence is identical to an RNA corresponding to any one of SEQ ID NOs: 1-1203 and 2411-3392. In some embodiments, the first nucleotide sequence is complementary to any one of SEQ ID NOs: 1204-2406 and 3393-4374.

An exemplary siNA molecule of the present disclosure is shown in FIG. 4. As shown in FIG. 4, an exemplary siNA molecule can comprise a sense strand (101) and an antisense strand (102). The sense strand (101) may comprise a first oligonucleotide sequence (103). The first oligonucleotide sequence (103) may comprise one or more phosphorothioate internucleoside linkages (109). The phosphorothioate internucleoside linkage (109) may be between the nucleotides at the 5′ or 3′ terminal end of the first oligonucleotide sequence (103). The phosphorothioate internucleoside linkage (109) may be between the first three nucleotides from the 5′ end of the first oligonucleotide sequence (103). The first oligonucleotide sequence (103) may comprise one or more 2′-fluoro nucleotides (110). The first oligonucleotide sequence (103) may comprise one or more 2′-O-methyl nucleotides (111). The first oligonucleotide sequence (103) may comprise 15 or more modified nucleotides independently selected from 2′-fluoro nucleotides (110) and 2′-O-methyl nucleotides (111). The sense strand (101) may further comprise a phosphorylation blocker (105). The sense strand (101) may further comprise an optional conjugated moiety (106). The antisense strand (102) may comprise a second oligonucleotide sequence (104). The second oligonucleotide sequence (104) may comprise one or more phophorothioate internucleoside linkages (109). The phosphorothioate internucleoside linkage (109) may be between the nucleotides at the 5′ or 3′ terminal end of the second oligonucleotide sequence (104). The phosphorothioate internucleoside linkage (109) may be between the first three nucleotides from the 5′ end of the second oligonucleotide sequence (104). The phosphorothioate internucleoside linkage (109) may be between the first three nucleotides from the 3′ end of the second oligonucleotide sequence (104). The second oligonucleotide sequence (104) may comprise one or more 2′-fluoro nucleotides (110). The second oligonucleotide sequence (104) may comprise one or more 2′-O-methyl nucleotides (111). The second oligonucleotide sequence (104) may comprise 15 or more modified nucleotides independently selected from 2′-fluoro nucleotides (110) and 2′-O-methyl nucleotides (111). The antisense strand (102) may further comprise a 5′-stabilized end cap (107). The siNA may further comprise one or more blunt ends. Alternatively, or additionally, one end of the siNA may comprise an overhang (108). The overhang (108) may be part of the sense strand (101). The overhang (108) may be part of the antisense strand (102). The overhang (108) may be distinct from the first nucleotide sequence (103). The overhang (108) may be distinct from the second nucleotide sequence (104). The overhang (108) may be part of the first nucleotide sequence (103). The overhang (108) may be part of the second nucleotide sequence (104). The overhang (108) may comprise 1 or more nucleotides. The overhang (108) may comprise 1 or more deoxyribonucleotides. The overhang (108) may comprise 1 or more modified nucleotides. The overhang (108) may comprise 1 or more modified ribonucleotides. The sense strand (101) may be shorter than the antisense strand (102). The sense strand (101) may be the same length as the antisense strand (102). The sense strand (101) may be longer than the antisense strand (102).

Another exemplary siNA molecule of the present disclosure is shown in FIG. 5. As shown in FIG. 5, an exemplary siNA molecule can comprise a sense strand (201) and an antisense strand (202). The sense strand (201) may comprise a first oligonucleotide sequence (203). The first oligonucleotide sequence (203) may comprise one or more phophorothioate internucleoside linkages (209). The phosphorothioate internucleoside linkage (209) may be between the nucleotides at the 5′ or 3′ terminal end of the first oligonucleotide sequence (203). The phosphorothioate internucleoside linkage (209) may be between the first three nucleotides from the 5′ end of the first oligonucleotide sequence (203). The first oligonucleotide sequence (203) may comprise one or more 2′-fluoro nucleotides (210). The first oligonucleotide sequence (203) may comprise one or more 2′-O-methyl nucleotides (211). The first oligonucleotide sequence (203) may comprise 15 or more modified nucleotides independently selected from 2′-fluoro nucleotides (210) and 2′-O-methyl nucleotides (211). The sense strand (201) may further comprise a phosphorylation blocker (205). The sense strand (201) may further comprise an optional conjugated moiety (206). The antisense strand (202) may comprise a second oligonucleotide sequence (204). The second oligonucleotide sequence (204) may comprise one or more phophorothioate internucleoside linkages (209). The phosphorothioate internucleoside linkage (209) may be between the nucleotides at the 5′ or 3′ terminal end of the second oligonucleotide sequence (204). The phosphorothioate internucleoside linkage (209) may be between the first three nucleotides from the 5′ end of the second oligonucleotide sequence (204). The phosphorothioate internucleoside linkage (209) may be between the first three nucleotides from the 3′ end of the second oligonucleotide sequence (204). The second oligonucleotide sequence (204) may comprise one or more 2′-fluoro nucleotides (210). The second oligonucleotide sequence (204) may comprise one or more 2′-O-methyl nucleotides (211). The second oligonucleotide sequence (204) may comprise 15 or more modified nucleotides independently selected from 2′-fluoro nucleotides (210) and 2′-O-methyl nucleotides (211). The antisense strand (202) may further comprise a 5′-stabilized end cap (207). The siNA may further comprise one or more overhangs (208). The overhang (208) may be part of the sense strand (201). The overhang (208) may be part of the antisense strand. (202). The overhang (208) may be distinct from the first nucleotide sequence (203). The overhang (208) may be distinct from the second nucleotide sequence (204). The overhang (208) may be part of the first nucleotide sequence (203). The overhang (208) may be part of the second nucleotide sequence (204). The overhang (208) may be adjacent to the 3′ end of the first nucleotide sequence (203). The overhang (208) may be adjacent to the 5′ end of the first nucleotide sequence (203). The overhang (208) may be adjacent to the 3′ end of the second nucleotide sequence (204). The overhang (208) may be adjacent to the 5′ end of the second nucleotide sequence (204). The overhang (208) may comprise 1 or more nucleotides. The overhang (208) may comprise 1 or more deoxyribonucleotides. The overhang (208) may comprise a TT sequence. The overhang (208) may comprise 1 or more modified nucleotides. The overhang (208) may comprise 1 or more modified nucleotides disclosed herein (e.g., 2-fluoro nucleotide, 2′-O-methyl nucleotide, 2′-fluoro nucleotide mimic, 2′-O-methyl nucleotide mimic, or a nucleotide comprising a modified nucleobase). The overhang (208) may comprise 1 or more modified ribonucleotides. The sense strand (201) may be shorter than the antisense strand (202). The sense strand (201) may be the same length as the antisense strand (202). The sense strand (201) may be longer than the antisense strand (202).

FIGS. 6A-6I depict exemplary ds-siNA modification patterns. As shown in FIGS. 6A-6G, an exemplary ds-siNA molecule may have the following formula:

5′-A_n¹B_n²A_n³B_n⁴A_n⁵B_n⁶A_n⁷B_n⁸A_n⁹-3′

3′-C_q¹A_q²B_q³A_q⁴B_q⁵A_q⁶B_q⁷A_q⁸B_q⁹A_q¹⁰B_q¹¹A_q¹²-5′

wherein:

the top strand is a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence comprises 15 to 30 nucleotides;

the bottom strand is an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence comprises 15 to 30 nucleotides;

each A is independently a 2′-O-methyl nucleotide or a nucleotide comprising a 5′ stabilized end cap or phosphorylation blocker;

B is a 2′-fluoro nucleotide;

C represents overhanging nucleotides and is a 2′-O-methyl nucleotide;

n¹=1-4 nucleotides in length;

each n², n⁶, n⁸, q³, q⁵, q⁷, q⁹, q¹¹, and q¹²is independently 0-1 nucleotides in length;

each n³and n⁴is independently 1-3 nucleotides in length;

n⁵is 1-10 nucleotides in length;

n⁷is 0-4 nucleotides in length;

each n⁹, q¹, and q²is independently 0-2 nucleotides in length;

q⁴is 0-3 nucleotides in length;

q⁶is 0-5 nucleotides in length;

q⁸is 2-7 nucleotides in length; and

q¹⁰is 2-11 nucleotides in length.

The ds-siNA may further comprise a conjugated moiety. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2 and positions 2 and 3 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the antisense strand. The ds-siNA may further comprise a 5′-stabilizing end cap. The 5′-stabilizing end cap may be a vinyl phosphonate. The 5′-stabilizing end cap may be attached to the 5′ end of the antisense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. An exemplary ds-siNA molecule may have the following formula:

5′-A_2-4B₁A_1-3B_2-3A_2-10B_0-1A_0-4B_0-1A_0-2-3′

3′-C₂A_0-2B_0-1A_0-3B_0-1A_0-5B_0-1A_2-7B₁A_2-11B₁A₁-5′

The ds-siNA may further comprise a conjugated moiety. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2 and positions 2 and 3 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the antisense strand. The ds-siNA may further comprise a 5′-stabilizing end cap. The 5′-stabilizing end cap may be a vinyl phosphonate. The vinyl phosphonate may be a deuterated vinyl phosphonate. The deuterated vinyl phosphonate may be a mono-deuterated vinyl phosphonate. The deuterated vinyl phosphonate may be a mono-di-deuterated vinyl phosphonate. The 5′-stabilizing end cap may be attached to the 5′ end of the antisense strand. The 5′-stabilizing end cap may be attached to the 3′ end of the antisense strand. The 5′-stabilizing end cap may be attached to the 5′ end of the sense strand. The 5′-stabilizing end cap may be attached to the 3′ end of the sense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker.

The exemplary ds-siNA shown in FIGS. 6A-6I comprise (i) a sense strand comprising 19-21 nucleotides; and (ii) an antisense strand comprising 21-23 nucleotides. The ds-siNA may further comprise (iii) an optional conjugated moiety, wherein the conjugated moiety is attached to the 3′ end of the antisense strand and, in some embodiments, no ps would be needed at the 3′-end of the sense strand if it is conjugated to a moiety and such conjugation my also result in removal of the 5′ overhang on the sense strand. The ds-siNA may comprise a 2-nucleotide overhang consisting of nucleotides at positions 20 and 21 from the 5′ end of the antisense strand. The ds-siNA may comprise a 2-nucleotide overhang consisting of nucleotides at positions 22 and 23 from the 5′ end of the antisense strand. The ds-siNA may further comprise 1, 2, 3, 4, 5, 6 or more phosphorothioate (ps) internucleoside linkages. At least one phosphorothioate internucleoside linkage may be between the nucleotides at positions 1 and 2 or positions 2 and 3 from the 5′ end of the sense strand. At least one phosphorothioate internucleoside linkage may be between the nucleotides at positions 1 and 2 or positions 2 and 3 from the 5′ end of the antisense strand. At least one phosphorothioate internucleoside linkage may be between the nucleotides at positions 19 and 20, positions 20 and 21, positions 21 and 22, or positions 22 and 23 from the 5′ end of the antisense strand. As shown in FIGS. 6A-6G, 4-6 nucleotides in the sense strand may be 2′-fluoro nucleotides. As shown in FIGS. 6A-6G, 2-5 nucleotides in the antisense strand may be 2′-fluoro nucleotides. As shown in FIGS. 6A-6G, 13-15 nucleotides in the sense strand may be 2′-O-methyl nucleotides. As shown in FIGS. 6A-6G, 14-19 nucleotides in the antisense strand may be 2′-O-methyl nucleotides. As shown in FIGS. 6A-6G, the ds-siNA does not contain a base pair between 2′-fluoro nucleotides on the sense and antisense strands. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker.

As shown in FIG. 6A, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 3, 7-9, 12, and 17 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 2, 4-6, 10, 11, 13-16, and 18-21 from the 5′ end of the sense strand; (b) an antisense strand consisting of 21 nucleotides, wherein nucleotides at positions 2 and 14 from the 5′ end of the antisense strand are 2′-fluoro nucleotides; and wherein nucleotides at positions 1, 3-13, and 15-21 are 2′-O-methyl nucleotides. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the antisense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6B, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 3, 7, 8, 12, and 17 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 2, 4-6, 9-11, 13-16, and 18-21 from the 5′ end of the sense strand; (b) an antisense strand consisting of 21 nucleotides, wherein nucleotides at positions 2 and 14 from the 5′ end of the antisense strand are 2′-fluoro nucleotides; and wherein nucleotides at positions 1, 3-13, and 15-21 are 2′-O-methyl nucleotides. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the antisense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6C, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 3, 7-9, 12, and 17 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 2, 4-6, 10, 11, 13-16, and 18-21 from the 5′ end of the sense strand; (b) an antisense strand consisting of 21 nucleotides, wherein the nucleotides in the antisense strand comprise an alternating 1:3 modification pattern, and wherein 1 nucleotide is a 2′-fluoro nucleotide and 3 nucleotides are 2′-O-methyl nucleotides. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; and positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the antisense strand. The ds-siNA may comprise 2-5 alternating 1:3 modification patterns on the antisense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6D, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 5 and 7-9 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1-4, 6, and 10-21 from the 5′ end of the sense strand; (b) an antisense strand consisting of 21 nucleotides, wherein the nucleotides in the antisense strand comprise an alternating 1:3 modification pattern, and wherein 1 nucleotide is a 2′-fluoro nucleotide and 3 nucleotides are 2′-O-methyl nucleotides. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the antisense strand. The ds-siNA may comprise 2-5 alternating 1:3 modification patterns on the antisense strand. The alternating 1:3 modification pattern may start at the nucleotide at any of positions 2, 6, 10, 14, and/or 18 from the 5′ end of the antisense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6E, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 5 and 7-9 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1-4, 6, and 10-21 from the 5′ end of the sense strand; (b) an antisense strand consisting of 21 nucleotides, wherein nucleotides at positions 2, 5, 8, 14, and 17 from the 5′ end of the antisense strand are 2′-fluoro nucleotides; and wherein nucleotides at positions 1, 3-13, and 15-21 are 2′-O-methyl nucleotides. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the antisense strand. The ds-siNA may comprise 2-5 alternating 1:2 modification patterns on the antisense strand. The alternating 1:2 modification pattern may start at the nucleotide at any of positions 2, 5, 8, 14, and/or 17 from the 5′ end of the antisense strand. In some embodiments, the ds-siNA comprises (a) a sense strand consisting of 19 nucleotides, wherein 2′-fluoro nucleotides are at positions 5 and 7-9 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1-4, 6, and 10-19 from the 5′ end of the sense strand; (b) an antisense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 2, 5, 8, 14, and 17 from the 5′ end of the antisense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 3, 4, 6, 7, 9-13, 15, 16, and 18-21 from the 5′ end of the sense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6F, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 5 and 7-9 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1-4, 6, and 10-21 from the 5′ end of the sense strand; (b) an antisense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 3-5, 7-13, 15, and 17-21 from the 5′ end of the antisense strand. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 19 and 20; and positions 20 and 21 from the 5′ end of the antisense strand. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a f4P nucleotide. In some embodiments, at least 1, 2, 3, or 4 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, at least one of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, at least two of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, less than or equal to 3 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, less than or equal to 2 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 2 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 6 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 14 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 16 from the 5′ end of the antisense strand is a f4P nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a f2P nucleotide. In some embodiments, at least 1, 2, 3, or 4 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, at least one of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, at least two of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, less than or equal to 3 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, less than or equal to 2 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 2 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 6 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 14 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 16 from the 5′ end of the antisense strand is a f2P nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a fX nucleotide. In some embodiments, at least 1, 2, 3, or 4 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, at least one of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, at least two of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, less than or equal to 3 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, less than or equal to 2 of the 2′-fluoro-nucleotides at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 2 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 6 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 14 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, the 2′-fluoro-nucleotide at position 16 from the 5′ end of the antisense strand is a fX nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6G, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 5, 9-11, 14, and 19 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1-4, 6-8, 12, 13, 15-18, 20, and 21 from the 5′ end of the sense strand; and (b) an antisense strand consisting of 23 nucleotides, wherein 2′-flouro nucleotides are at positions 2 and 14 from the 5′ end of the antisense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 3-13, and 15-23 from the 5′ end of the antisense strand. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 21 and 22; and positions 22 and 23 from the 5′ end of the antisense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6H, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 7 and 9-11 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1-6, 8, and 12-21 from the 5′ end of the sense strand; and (b) an antisense strand consisting of 23 nucleotides, wherein 2′-flouro nucleotides are at positions 2, 6, 14, and 16 from the 5′ end of the antisense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 3-5, 7-13, 15, and 17-23 from the 5′ end of the antisense strand. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 21 and 22; and positions 22 and 23 from the 5′ end of the antisense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

As shown in FIG. 6I, a ds-siNA may comprise (a) a sense strand consisting of 21 nucleotides, wherein 2′-fluoro nucleotides are at positions 7 and 9-11 from the 5′ end of the sense strand, and wherein 2′-O-methyl nucleotides are at positions 1-6, 8, and 12-21 from the 5′ end of the sense strand; and (b) an antisense strand consisting of 23 nucleotides, wherein 2′-flouro nucleotides are at positions 2, 5, 8, 14, 17, and 20 from the 5′ end of the antisense strand, and wherein 2′-O-methyl nucleotides are at positions 1, 3, 4, 6, 9-13, 15, 16, 18, 19, and 21-23 from the 5′ end of the antisense strand. The ds-siNA may further comprise a conjugated moiety attached to the 3′ end of the sense strand. The ds-siNA may further comprise (i) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; and positions 20 and 21 from the 5′ end of the sense strand; and (ii) phosphorothioate internucleoside linkages between the nucleotides at positions 1 and 2; positions 2 and 3; positions 21 and 22; and positions 22 and 23 from the 5′ end of the antisense strand. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a 5′ stabilizing end cap. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is further modified to contain a phosphorylation blocker. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 5′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the sense strand is a d2vd3 nucleotide. In some embodiments, the 2′-O-methyl nucleotide at position 1 from the 3′ end of the antisense strand is a d2vd3 nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand or antisense strand is a 2′-fluoro nucleotide mimic. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the sense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-fluoro nucleotides on the antisense strand is a f4P, f2P, or fX nucleotide. In some embodiments, at least 1, 2, 3, 4 or more 2′-O-methyl nucleotide on the sense or antisense strand is a 2′-O-methyl nucleotide mimic.

In some embodiments, the nucleotides in the antisense strand may comprise an alternating 1:2 modification pattern, wherein 1 nucleotide is a 2′-fluoro nucleotide and 2 nucleotides are 2′-O-methyl nucleotides. In some embodiments, the nucleotides in the antisense strand may comprise an alternating 1:1 modification pattern (i.e., an alternating pattern), wherein 1 nucleotide is a 2′-fluoro nucleotide and 1 nucleotide is a 2′-O-methyl nucleotide in an alternating fashion. These alternating modification patterns may start at any nucleotide of the antisense strand.

Any of the siNAs disclosed herein may comprise a sense strand and an antisense strand. The sense strand may comprise a first nucleotide sequence that is 15 to 30 nucleotides in length. The antisense strand may comprise a second nucleotide sequence that is 15 to 30 nucleotides in length.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of this disclosure may comprise: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 7 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 7, 9, 10, and/or 11 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and the nucleotide at position 2 of the second nucleotide sequence is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (iii) comprises 1 or more phosphorothioate internucleoside linkage; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (iii) comprises 1 or more phosphorothioate internucleoside linkage.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide, wherein the ds-siNA may further comprise a phosphorylation blocker and/or a 5′-stabilized end cap.

A double-stranded short interfering nucleic acid (ds-siNA) molecule comprises: (I) a sense strand comprising (A) a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (B) a phosphorylation blocker; and (II) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (a) is 15 to 30 nucleotides in length; and (b) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (I) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (a) is 15 to 30 nucleotides in length; and (b) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (II) an antisense strand comprising (A) a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (B) a 5′-stabilized end cap.

A double-stranded short interfering nucleic acid (ds-siNA) molecule of the disclosure may comprise: (I) a sense strand comprising (A) a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (B) a phosphorylation blocker; and (II) an antisense strand comprising (A) a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence: (i) is 15 to 30 nucleotides in length; and (ii) comprises 15 or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide, wherein at least one modified nucleotide is a 2′-O-methyl nucleotide and at least one modified nucleotide is a 2′-fluoro nucleotide; and (B) a 5′-stabilized end cap.

A double-stranded short interfering nucleic acid (ds-siNA) molecule comprises: (a) a sense strand comprising a first nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identical to an RNA corresponding to a target gene, wherein the first nucleotide sequence comprises a nucleotide sequence as shown in Table 2; and (b) an antisense strand comprising a second nucleotide sequence that is at least about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% complementary to the RNA corresponding to the target gene, wherein the second nucleotide sequence comprises a nucleotide sequence as shown in Table 2.

Further disclosed herein are compositions comprising two or more of the siNA molecules described herein. Further disclosed herein are compositions comprising any of the siNA molecule described and a pharmaceutically acceptable carrier or diluent. Further disclosed herein are compositions comprising two or more of the siNA molecules described herein for use as a medicament. Further disclosed herein are compositions comprising any of the siNA molecule described and a pharmaceutically acceptable carrier or diluent for use as a medicament.

Further disclosed herein are methods of treating an infection (e.g., COVID-19) in a subject in need thereof, the method comprising administering to the subject any of the siNA molecules described herein. Further disclosed herein are uses of any of the siNA molecules described herein in the manufacture of a medicament for treating an infection (e.g., COVID-19).

A. siNA Sense Strand

Any of the siNA molecules or oligomers described herein may comprise a sense strand. The sense strand may comprise a first nucleotide sequence. The first nucleotide sequence may be 15 to 30, 15 to 25, 15 to 23, 17 to 23, 19 to 23, or 19 to 21 nucleotides in length. In some embodiments, the first nucleotide sequence is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. In some embodiments, the first nucleotide sequence is at least 19 nucleotides in length. In some embodiments, the first nucleotide sequence is at least 21 nucleotides in length.

In some embodiments, the sense strand is the same length as the first nucleotide sequence. In some embodiments, the sense strand is longer than the first nucleotide sequence. In some embodiments, the sense strand may further comprise 1, 2, 3, 4, or 5 or more nucleotides than the first nucleotide sequence. In some embodiments, the sense strand may further comprise a deoxyribonucleic acid (DNA). In some embodiments, the DNA is thymine (T). In some embodiments, the sense strand may further comprise a TT sequence. In some embodiments, the TT sequence is adjacent to the first nucleotide sequence. In some embodiments, the sense strand may further comprise one or more modified nucleotides that are adjacent to the first nucleotide sequence. In some embodiments, the one or more modified nucleotides are independently selected from any of the modified nucleotides disclosed herein (e.g., 2′-fluoro nucleotide, 2′-O-methyl nucleotide, 2′-fluoro nucleotide mimic, 2′-O-methyl nucleotide mimic, or a nucleotide comprising a modified nucleobase).

In some embodiments, at least one end of the ds-siNA may be a blunt end. In some embodiments, at least one end of the ds-siNA may comprise an overhang, wherein the overhang comprises at least one nucleotide. In some embodiments, both ends of the ds-siNA may comprise an overhang, wherein the overhang comprises at least one nucleotide.

In some embodiments, the first nucleotide sequence comprises 15, 16, 17, 18, 19, 20, 21, 22, 23, or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In some embodiments, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotides in the first nucleotide sequence are modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In some embodiments, 100% of the nucleotides in the first nucleotide sequence are modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In some embodiments, the 2′-O-methyl nucleotide is a 2′-O-methyl nucleotide mimic. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic.

In some embodiments, between about 15 to 30, 15 to 25, 15 to 24, 15 to 23, 15 to 22, 15 to 21, 17 to 30, 17 to 25, 17 to 24, 17 to 23, 17 to 22, 17 to 21, 18 to 30, 18 to 25, 18 to 24, 18 to 23, 18 to 22, 18 to 21, 19 to 30, 19 to 25, 19 to 24, 19 to 23, 19 to 22, 19 to 21, 20 to 25, 20 to 24, 20 to 23, 21 to 25, 21 to 24, or 21 to 23 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, between about 2 to 20 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, between about 5 to 25 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, between about 10 to 25 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, between about 12 to 25 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 12 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 13 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 14 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 15 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 16 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 17 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 18 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 19 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 21 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 20 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 19 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 18 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 17 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 16 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 15 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 14 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 13 modified nucleotides of the first nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least one modified nucleotide of the first nucleotide sequence is a 2′-O-methyl pyrimidine. In some embodiments, at least 5, 6, 7, 8, 9, or 10 modified nucleotides of the first nucleotide sequence are 2′-O-methyl pyrimidines. In some embodiments, at least one modified nucleotide of the first nucleotide sequence is a 2′-O-methyl purine. In some embodiments, at least 5, 6, 7, 8, 9, or 10 modified nucleotides of the first nucleotide sequence are 2′-O-methyl purines. In some embodiments, the 2′-O-methyl nucleotide is a 2′-O-methyl nucleotide mimic.

In some embodiments, between 2 to 15 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, between 2 to 10 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, between 2 to 6 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 1 to 6, 1 to 5, 1 to 4, or 1 to 3 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 1, 2, 3, 4, 5, or 6 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 1 modified nucleotide of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, at least 2 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 3 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 4 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 5 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 6 modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 10, 9, 8, 7, 6, 5, 4, 3 or fewer modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 10 or fewer modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 7 or fewer modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 6 or fewer modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 5 or fewer modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 4 or fewer modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 3 or fewer modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 2 or fewer modified nucleotides of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least one modified nucleotide of the first nucleotide sequence is a 2′-fluoro pyrimidine. In some embodiments, 1, 2, 3, 4, 5, or 6 modified nucleotides of the first nucleotide sequence are 2′-fluoro pyrimidines. In some embodiments, at least one modified nucleotide of the first nucleotide sequence is a 2′-fluoro purine. In some embodiments, 1, 2, 3, 4, 5, or 6 modified nucleotides of the first nucleotide sequence are 2′-fluoro purines. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic.

In some embodiments, the nucleotide at position 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, at least two nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least three nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least four nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least five nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotide at position 3 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 7 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 8 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 9 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 12 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 17 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic.

In some embodiments, at least 1, 2, 3, 4, 5, 6, or 7 nucleotides at position 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, at least two nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least three nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotides at positions 3, 5, 7, 8, 9, 10, 11, 12, 14, 17, and/or 19 from the 5′ end of the first nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotide at position 3 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 5 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 7 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 8 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 9 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 10 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 11 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 12 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 14 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 17 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 19 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 3, 7, 8, 9, 12, and/or 17 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 3, 7, 8, and/or 17 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 3, 7, 8, 9, 12, and/or 17 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 5, 7, 8, and/or 9 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 5, 9, 10, 11, 12, and/or 19 from the 5′ end of the first nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoro nucleotide mimic can be selected from

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In some embodiments, the 2′-fluoro nucleotide or 2′-O-methyl nucleotide is a 2′-fluoro or 2′-O-methyl nucleotide mimic. In some embodiments, the 2′-fluoro or 2′-O-methyl nucleotide mimic is a nucleotide mimic of Formula (V):

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wherein R¹is a independently nucleobase, aryl, heteroaryl, or H, Q¹and Q²are independently S or O, R⁵is independently —OCD₃, —F, or —OCH₃, and R⁶and R⁷are independently H, D, or CD₃. In some embodiments, the nucleobase is selected from cytosine, guanine, adenine, uracil, aryl, heteroaryl, and an analogue or derivative thereof.

In some embodiments, the 2′-fluoro or 2′-O-methyl nucleotide mimic is a nucleotide mimic of Formula (16)-Formula (20):

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wherein R¹is independently a nucleobase and R²is F or —OCH₃. In some embodiments, the nucleobase is selected from cytosine, guanine, adenine, uracil, aryl, heteroaryl, and an analogue or derivative thereof.

In some embodiments, the first nucleotide sequence comprises, consists of, or consists essentially of ribonucleic acids (RNAs). In some embodiments, the first nucleotide sequence comprises, consists of, or consists essentially of modified RNAs. In some embodiments, the modified RNAs are selected from a 2′-O-methyl RNA and 2′-fluoro RNA. In some embodiments, 15, 16, 17, 18, 19, 20, 21, 22, or 23 modified nucleotides of the first nucleotide sequence are independently selected from 2′-O-methyl RNA and 2′-fluoro RNA.

In some embodiments, the sense strand may further comprise one or more internucleoside linkages independently selected from a phosphodiester (PO) internucleoside linkage, phosphorothioate (PS) internucleoside linkage, phosphorodithioate internucleoside linkage, and PS-mimic internucleoside linkage. In some embodiments, the PS-mimic internucleoside linkage is a sulfo internucleotide linkage.

In some embodiments, the sense strand may further comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or more phosphorothioate internucleoside linkages. In some embodiments, the sense strand comprises 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, or 3 or fewer phosphorothioate internucleoside linkages. In some embodiments, the sense strand comprises 2 to 10, 2 to 8, 2 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2 phosphorothioate internucleoside linkages. In some embodiments, the sense strand comprises 1 to 2 phosphorothioate internucleoside linkages. In some embodiments, the sense strand comprises 2 to 4 phosphorothioate internucleoside linkages. In some embodiments, at least one phosphorothioate internucleoside linkage is between the nucleotides at positions 1 and 2 from the 5′ end of the first nucleotide sequence. In some embodiments, at least one phosphorothioate internucleoside linkage is between the nucleotides at positions 2 and 3 from the 5′ end of the first nucleotide sequence. In some embodiments, the sense strand comprises two phosphorothioate internucleoside linkages between the nucleotides at positions 1 to 3 from the 5′ end of the first nucleotide sequence.

In some embodiments, any of the sense strands disclosed herein may comprise a 5′ end cap monomer. In some embodiments, any of the first nucleotide sequences disclosed herein may comprise a 5′ end cap monomer.

B. siNA Antisense Strand

Any of the siNA molecules described herein may comprise an antisense strand. The antisense strand may comprise a second nucleotide sequence. The second nucleotide sequence may be 15 to 30, 15 to 25, 15 to 23, 17 to 23, 19 to 23, or 19 to 21 nucleotides in length. In some embodiments, the second nucleotide sequence is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. In some embodiments, the second nucleotide sequence is at least 19 nucleotides in length. In some embodiments, the second nucleotide sequence is at least 21 nucleotides in length.

In some embodiments, the antisense strand is the same length as the second nucleotide sequence. In some embodiments, the antisense strand is longer than the second nucleotide sequence. In some embodiments, the antisense strand may further comprise 1, 2, 3, 4, or 5 or more nucleotides than the second nucleotide sequence. In some embodiments, the antisense strand is the same length as the sense strand. In some embodiments, the antisense strand is longer than the sense strand. In some embodiments, the antisense strand may further comprise 1, 2, 3, 4, or 5 or more nucleotides than the sense strand. In some embodiments, the antisense strand may further comprise a deoxyribonucleic acid (DNA). In some embodiments, the DNA is thymine (T). In some embodiments, the antisense strand may further comprise a TT sequence. In some embodiments, the antisense strand may further comprise one or more modified nucleotides that are adjacent to the second nucleotide sequence. In some embodiments, the one or more modified nucleotides are independently selected from any of the modified nucleotides disclosed herein (e.g., 2′-fluoro nucleotide, 2′-O-methyl nucleotide, 2′-fluoro nucleotide mimic, 2′-O-methyl nucleotide mimic, or a nucleotide comprising a modified nucleobase).

In some embodiments, the second nucleotide sequence comprises 15, 16, 17, 18, 19, 20, 21, 22, 23, or more modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In some embodiments, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotides in the second nucleotide sequence are modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide. In some embodiments, 100% of the nucleotides in the second nucleotide sequence are modified nucleotides independently selected from a 2′-O-methyl nucleotide and a 2′-fluoro nucleotide.

In some embodiments, between about 15 to 30, 15 to 25, 15 to 24, 15 to 23, 15 to 22, 15 to 21, 17 to 30, 17 to 25, 17 to 24, 17 to 23, 17 to 22, 17 to 21, 18 to 30, 18 to 25, 18 to 24, 18 to 23, 18 to 22, 18 to 21, 19 to 30, 19 to 25, 19 to 24, 19 to 23, 19 to 22, 19 to 21, 20 to 25, 20 to 24, 20 to 23, 21 to 25, 21 to 24, or 21 to 23 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, between about 2 to 20 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, between about 5 to 25 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, between about 10 to 25 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, between about 12 to 25 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, or 22 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 12 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 13 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 14 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 15 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 16 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 17 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 18 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least about 19 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 21 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 20 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 19 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 18 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 17 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 16 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 15 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 14 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, less than or equal to 13 modified nucleotides of the second nucleotide sequence are 2′-O-methyl nucleotides. In some embodiments, at least one modified nucleotide of the second nucleotide sequence is a 2′-O-methyl pyrimidine. In some embodiments, at least 5, 6, 7, 8, 9, or 10 modified nucleotides of the second nucleotide sequence are 2′-O-methyl pyrimidines. In some embodiments, at least one modified nucleotide of the second nucleotide sequence is a 2′-O-methyl purine. In some embodiments, at least 5, 6, 7, 8, 9, or 10 modified nucleotides of the second nucleotide sequence are 2′-O-methyl purines. In some embodiments, the 2′-O-methyl nucleotide is a 2′-O-methyl nucleotide mimic.

In some embodiments, between 2 to 15 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, between 2 to 10 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, between 2 to 6 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 1 to 6, 1 to 5, 1 to 4, or 1 to 3 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 1, 2, 3, 4, 5, or 6 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 1 modified nucleotide of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, at least 2 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 3 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 4 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least 5 modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 10, 9, 8, 7, 6, 5, 4, 3 or fewer modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 10 or fewer modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 7 or fewer modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 6 or fewer modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 5 or fewer modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 4 or fewer modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 3 or fewer modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, 2 or fewer modified nucleotides of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least one modified nucleotide of the second nucleotide sequence is a 2′-fluoro pyrimidine. In some embodiments, 1, 2, 3, 4, 5, or 6 modified nucleotides of the second nucleotide sequence are 2′-fluoro pyrimidines. In some embodiments, at least one modified nucleotide of the second nucleotide sequence is a 2′-fluoro purine. In some embodiments, 1, 2, 3, 4, 5, or 6 modified nucleotides of the second nucleotide sequence are 2′-fluoro purines. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoro nucleotide mimic can be selected from

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wherein R¹is independently a nucleobase, aryl, heteroaryl, or H, Q¹and Q²are independently S or O, R⁵is independently —OCD₃, —F, or —OCH₃, and R⁶and R⁷are independently H, D, or CD₃. In some embodiments, the nucleobase is selected from cytosine, guanine, adenine, uracil, aryl, heteroaryl, and an analogue or derivative thereof.

In some embodiments, the 2′-fluoro or 2′-O-methyl nucleotide mimic is a nucleotide mimic of Formula (16)-Formula (20):

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wherein R¹is a nucleobase and R²is independently F or —OCH₃. In some embodiments, the nucleobase is selected from cytosine, guanine, adenine, uracil, aryl, heteroaryl, and an analogue or derivative thereof.

In some embodiments, at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 nucleotides at position 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, at least two nucleotides at positions 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least three nucleotides at positions 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least four nucleotides at positions 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, at least five nucleotides at positions 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotides at positions 2 and/or 14 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotides at positions 2, 6, and/or 16 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotides at positions 2, 6, 14, and/or 16 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotides at positions 2, 6, 10, 14, and/or 18 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotides at positions 2, 5, 8, 14, and/or 17 from the 5′ end of the second nucleotide sequence are 2′-fluoro nucleotides. In some embodiments, the nucleotide at position 2 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 5 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 6 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 8 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 10 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 14 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 16 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 17 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the nucleotide at position 18 from the 5′ end of the second nucleotide sequence is a 2′-fluoro nucleotide. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoro nucleotide mimic can be selected from

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In some embodiments, the nucleotides in the second nucleotide sequence are arranged in an alternating 1:3 modification pattern, wherein 1 nucleotide is a 2′-fluoro nucleotide and 3 nucleotides are 2′-O-methyl nucleotides, and wherein the alternating 1:3 modification pattern occurs at least 2 times. In some embodiments, the alternating 1:3 modification pattern occurs 2-5 times. In some embodiments, at least two of the alternating 1:3 modification pattern occur consecutively. In some embodiments, at least two of the alternating 1:3 modification pattern occurs nonconsecutively. In some embodiments, at least 1, 2, 3, 4, or 5 alternating 1:3 modification pattern begins at nucleotide position 2, 6, 10, 14, and/or 18 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:3 modification pattern begins at nucleotide position 2 from the 5′ end of the antisense strand. In some embodiments, wherein at least one alternating 1:3 modification pattern begins at nucleotide position 6 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:3 modification pattern begins at nucleotide position 10 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:3 modification pattern begins at nucleotide position 14 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:3 modification pattern begins at nucleotide position 18 from the 5′ end of the antisense strand. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoro nucleotide mimic can be selected from

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In some embodiments, the nucleotides in the second nucleotide sequence are arranged in an alternating 1:2 modification pattern, wherein 1 nucleotide is a 2′-fluoro nucleotide and 2 nucleotides are 2′-O-methyl nucleotides, and wherein the alternating 1:2 modification pattern occurs at least 2 times. In some embodiments, the alternating 1:2 modification pattern occurs 2-5 times. In some embodiments, at least two of the alternating 1:2 modification pattern occurs consecutively. In some embodiments, at least two of the alternating 1:2 modification pattern occurs nonconsecutively. In some embodiments, at least 1, 2, 3, 4, or 5 alternating 1:2 modification pattern begins at nucleotide position 2, 5, 8, 14, and/or 17 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:2 modification pattern begins at nucleotide position 2 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:2 modification pattern begins at nucleotide position 5 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:2 modification pattern begins at nucleotide position 8 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:2 modification pattern begins at nucleotide position 14 from the 5′ end of the antisense strand. In some embodiments, at least one alternating 1:2 modification pattern begins at nucleotide position 17 from the 5′ end of the antisense strand. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoro nucleotide mimic can be selected from

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In some embodiments, the second nucleotide sequence comprises, consists of, or consists essentially of ribonucleic acids (RNAs). In some embodiments, the second nucleotide sequence comprises, consists of, or consists essentially of modified RNAs. In some embodiments, the modified RNAs are selected from a 2′-O-methyl RNA and 2′-fluoro RNA. In some embodiments, 15, 16, 17, 18, 19, 20, 21, 22, or 23 modified nucleotides of the second nucleotide sequence are independently selected from 2′-O-methyl RNA and 2′-fluoro RNA. In some embodiments, the 2′-fluoro nucleotide is a 2′-fluoro nucleotide mimic. The 2′-fluoro nucleotide mimic can be selected from

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In some embodiments, the sense strand may further comprise one or more internucleotide linkages independently selected from a phosphodiester (PO) internucleoside linkage, phosphorothioate (PS) internucleoside linkage, phosphorodithioate internucleoside linkage, and PS-mimic internucleoside linkage. In some embodiments, the PS-mimic internucleoside linkage is a sulfo internucleotide linkage.

In some embodiments, the antisense strand may further comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or more phosphorothioate internucleoside linkages. In some embodiments, the antisense strand comprises 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, or 3 or fewer phosphorothioate internucleoside linkages. In some embodiments, the antisense strand comprises 2 to 10, 2 to 8, 2 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2 phosphorothioate internucleoside linkages. In some embodiments, the antisense strand comprises 2 to 10, 2 to 8, 2 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2 phosphorothioate internucleoside linkages. In some embodiments, the antisense strand comprises 2 to 8 phosphorothioate internucleoside linkages. In some embodiments, the antisense strand comprises 3 to 8 phosphorothioate internucleoside linkages. In some embodiments, the antisense strand comprises 4 to 8 phosphorothioate internucleoside linkages. In some embodiments, at least one phosphorothioate internucleoside linkage is between the nucleotides at positions 1 and 2 from the 5′ end of the second nucleotide sequence. In some embodiments, at least one phosphorothioate internucleoside linkage is between the nucleotides at positions 2 and 3 from the 5′ end of the second nucleotide sequence.

In some embodiments, at least one phosphorothioate internucleoside linkage is between the nucleotides at positions 1 and 2 from the 3′ end of the second nucleotide sequence. In some embodiments, at least one phosphorothioate internucleoside linkage is between the nucleotides at positions 2 and 3 from the 3′ end of the second nucleotide sequence. In some embodiments, the antisense strand comprises two phosphorothioate internucleoside linkages between the nucleotides at positions 1 to 3 from the 5′ end of the first nucleotide sequence. In some embodiments, the antisense strand comprises two phosphorothioate internucleoside linkages between the nucleotides at positions 1 to 3 from the 3′ end of the first nucleotide sequence. In some embodiments, the antisense strand comprises (a) two phosphorothioate internucleoside linkages between the nucleotides at positions 1 to 3 from the 5′ end of the first nucleotide sequence; and (b) two phosphorothioate internucleoside linkages between the nucleotides at positions 1 to 3 from the 3′ end of the first nucleotide sequence.

In some embodiments, at least one end of the ds-siNA is a blunt end. In some embodiments, at least one end of the ds-siNA comprises an overhang, wherein the overhang comprises at least one nucleotide. In some embodiments, both ends of the ds-siNA comprise an overhang, wherein the overhang comprises at least one nucleotide. In some embodiments, the overhang comprises 1 to 5 nucleotides, 1 to 4 nucleotides, 1 to 3 nucleotides, or 1 to 2 nucleotides. In some embodiments, the overhang consists of 1 to 2 nucleotides.

In some embodiments, any of the antisense strands disclosed herein may comprise a 5′ end cap monomer. In some embodiments, any of the second nucleotide sequences disclosed herein may comprise a 5′ end cap monomer.

Modified Nucleotides

Further disclosed herein are siNA molecules comprising one or more modified nucleotides. In some embodiments, any of the siNAs disclosed herein comprise one or more modified nucleotides. In some embodiments, any of the sense strands disclosed herein comprise one or more modified nucleotides. In some embodiments, any of the first nucleotide sequences disclosed herein comprise one or more modified nucleotides. In some embodiments, any of the antisense strands disclosed herein comprise one or more modified nucleotides. In some embodiments, any of the second nucleotide sequences disclosed herein comprise one or more modified nucleotides. In some embodiments, the one or more modified nucleotides is adjacent to the first nucleotide sequence. In some embodiments, at least one modified nucleotide is adjacent to the 5′ end of the first nucleotide sequence. In some embodiments, at least one modified nucleotide is adjacent to the 3′ end of the first nucleotide sequence. In some embodiments, at least one modified nucleotide is adjacent to the 5′ end of the first nucleotide sequence and at least one modified nucleotide is adjacent to the 3′ end of the first nucleotide sequence. In some embodiments, the one or more modified nucleotides is adjacent to the second nucleotide sequence. In some embodiments, at least one modified nucleotide is adjacent to the 5′ end of the second nucleotide sequence. In some embodiments, at least one modified nucleotide is adjacent to the 3′ end of the second nucleotide sequence. In some embodiments, at least one modified nucleotide is adjacent to the 5′ end of the second nucleotide sequence and at least one modified nucleotide is adjacent to the 3′ end of the second nucleotide sequence. In some embodiments, a 2′-O-methyl nucleotide in any of sense strands or first nucleotide sequences disclosed herein is replaced with a modified nucleotide. In some embodiments, a 2′-O-methyl nucleotide in any of antisense strands or second nucleotide sequences disclosed herein is replaced with a modified nucleotide.

In some embodiments, any of the siNA molecules, siNAs, sense strands, first nucleotide sequences, antisense strands, and second nucleotide sequences disclosed herein comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 or more modified nucleotides. In some embodiments, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 70%, 75%, 80%, 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of the nucleotides in the siNA molecule, siNA, sense strand, first nucleotide sequence, antisense strand, or second nucleotide sequence are modified nucleotides.

In some embodiments, a modified nucleotide is selected from the group consisting of 2′-fluoro nucleotide, 2′-O-methyl nucleotide, 2′-fluoro nucleotide mimic, 2′-O-methyl nucleotide mimic, a locked nucleic acid, and a nucleotide comprising a modified nucleobase.

In some embodiments, any of the siRNAs disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more 2′-fluoro or 2′-O-methyl nucleotide mimics. In some embodiments, any of the sense strands disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more 2′-fluoro or 2′-O-methyl nucleotide mimics. In some embodiments, any of the first nucleotide sequences disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more 2′-fluoro or 2′-O-methyl nucleotide mimics. In some embodiments, any of the antisense strand disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more 2′-fluoro or 2′-O-methyl nucleotide mimics. In some embodiments, any of the second nucleotide sequences disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more 2′-fluoro or 2′-O-methyl nucleotide mimics. In some embodiments, the 2′-fluoro or 2′-O-methyl nucleotide mimic is a nucleotide mimic of Formula (16)-Formula (20):

embedded image

wherein R¹is a nucleobase and R¹is independently F or —OCH₃. In some embodiments, the nucleobase is selected from cytosine, guanine, adenine, uracil, aryl, heteroaryl, and an analogue or derivative thereof.

In some embodiments, the siNA molecules disclosed herein comprise at least one 2′-fluoro nucleotide, at least one 2′-O-methyl nucleotide, and at least one 2′-fluoro or 2′-O-methyl nucleotide mimic. In some embodiments, the at least one 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent to the first nucleotide sequence. In some embodiments, the at least one 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent to the 5′ end of first nucleotide sequence. In some embodiments, the at least one 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent to the 3′ end of first nucleotide sequence. In some embodiments, the at least one 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent to the second nucleotide sequence. In some embodiments, the at least one 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent to the 5′ end of second nucleotide sequence. In some embodiments, the at least one 2′-fluoro or 2′-O-methyl nucleotide mimic is adjacent to the 3′ end of second nucleotide sequence. In some embodiments, the first nucleotide sequence does not comprise a 2′-fluoro nucleotide mimic. In some embodiments, the first nucleotide sequence does not comprise a 2′-O-methyl nucleotide mimic. In some embodiments, the second nucleotide sequence does not comprise a 2′-fluoro nucleotide mimic. In some embodiments, the second nucleotide sequence does not comprise a 2′-O-methyl nucleotide mimic.

In some embodiments, any of the siRNAs disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more locked nucleic acids. In some embodiments, any of the sense strands disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more locked nucleic acids. In some embodiments, any of the first nucleotide sequences disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more locked nucleic acids. In some embodiments, any of the antisense strand disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more locked nucleic acids. In some embodiments, any of the second nucleotide sequences disclosed herein comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more locked nucleic acids. In some embodiments, the locked nucleic acid is selected from

embedded image

where R is H or alkyl (or AmNA(N-Me)) when R is alkyl);

embedded image

wherein B is a nucleobase. In some embodiments, any of the siRNAs, sense strands, first nucleotide sequences, antisense strands, or second nucleotide sequences disclosed herein comprise at least modified nucleotide that is

embedded image

In some embodiments, any of the siRNAs, sense strands, first nucleotide sequences, antisense strands, or second nucleotide sequences disclosed herein comprise at least modified nucleotide that is

embedded image

In some embodiments, any of the siRNAs, sense strands, first nucleotide sequences, antisense strands, or second nucleotide sequences disclosed herein comprise at least modified nucleotide that is

embedded image

where R is H or alkyl (or AmNA(N-Me)) when R is alkyl). In some embodiments, any of the siRNAs, sense strands, first nucleotide sequences, antisense strands, or second nucleotide sequences disclosed herein comprise at least modified nucleotide that is

embedded image

In some embodiments, any of the siRNAs, sense strands, first nucleotide sequences, antisense strands, or second nucleotide sequences disclosed herein comprise at least modified nucleotide that is

embedded image

wherein B is a nucleobase.

Phosphorylation Blocker

Further disclosed herein are siNA molecules comprising a phosphorylation blocker. In some embodiments, a 2′-O-methyl nucleotide in any of sense strands or first nucleotide sequences disclosed herein is replaced with a nucleotide containing a phosphorylation blocker. In some embodiments, a 2′-O-methyl nucleotide in any of antisense strands or second nucleotide sequences disclosed herein is replaced with a nucleotide containing a phosphorylation blocker. In some embodiments, a 2′-O-methyl nucleotide in any of sense strands or first nucleotide sequences disclosed herein is further modified to contain a phosphorylation blocker. In some embodiments, a 2′-O-methyl nucleotide in any of antisense strands or second nucleotide sequences disclosed herein is further modified to contain a phosphorylation blocker.

In some embodiments, any of the siNA molecules disclosed herein comprise a phosphorylation blocker of Formula (IV):

embedded image

In some embodiments, any of the siNA molecules disclosed herein comprise a phosphorylation blocker of Formula (IV):

embedded image

wherein R¹is a nucleobase, and R⁴is —OCH₃or —N(CH₂CH₂)₂O.

In some embodiments, a siNA molecule comprises (a) a phosphorylation blocker of Formula (IV):

embedded image

In some embodiments, a siNA molecule comprises (a) a phosphorylation blocker of Formula (IV):

embedded image

wherein R¹is a nucleobase, and R⁴is —OCH₃or —N(CH₂CH₂)₂O; and (b) siNA, wherein the phosphorylation blocker is conjugated to the siNA.

In some embodiments, the phosphorylation blocker is attached to the 3′ end of the sense strand or first nucleotide sequence. In some embodiments, the phosphorylation blocker is attached to the 3′ end of the sense strand or first nucleotide sequence via 1, 2, 3, 4, or 5 or more linkers. In some embodiments, the phosphorylation blocker is attached to the 5′ end of the sense strand or first nucleotide sequence. In some embodiments, the phosphorylation blocker is attached to the 5′ end of the sense strand or first nucleotide sequence via 1, 2, 3, 4, or 5 or more linkers. In some embodiments, the phosphorylation blocker is attached to the 3′ end of the antisense strand or second nucleotide sequence. In some embodiments, the phosphorylation blocker is attached to the 3′ end of the antisense strand or second nucleotide sequence via 1, 2, 3, 4, or 5 or more linkers. In some embodiments, the phosphorylation blocker is attached to the 5′ end of the antisense strand or second nucleotide sequence. In some embodiments, the phosphorylation blocker is attached to the 5′ end of the antisense strand or second nucleotide sequence via 1, 2, 3, 4, or 5 or more linkers. In some embodiments, the one or more linkers are independently selected from the group consisting of a phosphodiester linker, phosphorothioate linker, and phosphorodithioate linker.

5′-Stabilized End Cap

Further disclosed herein are siNA molecules comprising a 5′-stabilized end cap. As used herein the terms “5′-stabilized end cap” and “5′ end cap” are used interchangeably. In some embodiments, a 2′-O-methyl nucleotide in any of sense strands or first nucleotide sequences disclosed herein is replaced with a nucleotide containing a 5′-stabilized end cap. In some embodiments, a 2′-O-methyl nucleotide in any of antisense strands or second nucleotide sequences disclosed herein is replaced with a nucleotide containing a 5′-stabilized end cap. In some embodiments, a 2′-O-methyl nucleotide in any of sense strands or first nucleotide sequences disclosed herein is further modified to contain a 5′-stabilized end cap. In some embodiments, a 2′-O-methyl nucleotide in any of antisense strands or second nucleotide sequences disclosed herein is further modified to contain a 5′-stabilized end cap.

In some embodiments, the 5′-stabilized end cap is a 5′ phosphate mimic. In some embodiments, the 5′-stabilized end cap is a modified 5′ phosphate mimic. In some embodiments, the modified 5′ phosphate is a chemically modified 5′ phosphate. In some embodiments, the 5′-stabilized end cap is a 5′-vinyl phosphonate. In some embodiments, the 5′-vinyl phosphonate is a 5′-(E)-vinyl phosphonate or 5′-(Z)-vinyl phosphonate. In some embodiments, the 5′-vinylphosphonate is a deuterated vinyl phosphonate. In some embodiments, the deuterated vinyl phosphonate is a mono-deuterated vinyl phosphonate. In some embodiments, the deuterated vinyl phosphonate is a di-deuterated vinyl phosphonate. In some embodiments, the 5′-stabilized end cap is a phosphate mimic. Examples of phosphate mimics are disclosed in Parmar et al., 2018, J Med Chem, 61(3):734-744, International Publication Nos. WO2018/045317 and WO2018/044350, and U.S. Pat. No. 10,087,210, each of which is incorporated by reference in its entirety.

In some embodiments, any of the siNA molecules, sense strands, first nucleotide sequences, antisense strands, or second nucleotide sequences disclosed herein comprise a 5′-stabilized end cap of Formula (Ia):

embedded image

wherein R¹is H, a nucleobase, aryl, or heteroaryl; R²is

embedded image

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_n—Z, or —(C₂-C₆alkenylene)-Z and R²⁰is H; or R²and R²⁰together form a 3- to 7-membered carbocyclic ring substituted with —(CR²¹R²²)_n—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4; Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_mCO₂R²³, —OP(S)OH(CH₂)_mCO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_mP(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴, —NR²³SO₂R²⁵; either R²¹and R²²are independently hydrogen or C₁-C₆alkyl, or R²¹and R²²together form an oxo group; R²³is hydrogen or C₁-C₆alkyl; R²⁴is —SO₂R²⁵or —C(O)R²⁵; or R²³and R²⁴together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic ring; R²⁵is C₁-C₆alkyl; and m is 1, 2, 3, or 4. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

embedded image

wherein R¹is H, a nucleobase, aryl, or heteroaryl; R²is

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl, or H,

R²is

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R²³and R²⁴together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic ring; R²⁵is C₁-C₆alkyl; and m is 1, 2, 3, or 4. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl,

or H, R²is

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—CH₂SO₂NHCH₃, or

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R⁹is —SO₂CH₃or —COCH₃, custom-character is a double or single bond, R¹⁰=—CH₂PO₃H or —NHCH₃, R¹¹is —CH₂— or —CO—, and R¹²is H and R¹¹is CH₃or R¹²and R¹¹together form —CH₂CH₂CH₂—. In some embodiments, le is an aryl. In some embodiments, the aryl is a phenyl.

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wherein R¹is a nucleobase, aryl, heteroaryl, or H, R²is

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—CH₂SO₂NHCH₃, or

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R⁹is —SO₂CH₃or —COCH₃, custom-character is a double or single bond, R¹⁰=—CH₂PO₃H or —NHCH₃, is —CH₂— or —CO—, and R¹²is H and R¹³is CH₃or R¹²and R¹³together form —CH₂CH₂CH₂—. In some embodiments, le is an aryl. In some embodiments, the aryl is a phenyl.

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wherein R¹is a nucleobase, aryl, heteroaryl, or H, L is —CH₂—, —CH═CH—, —CO—, or —CH₂CH₂—, and A is —ONHCOCH₃, —ONHSO₂CH₃, —PO₃H, —OP(SOH)CH₂CO₂H, —SO₂CH₂PO₃H, —SO₂NHCH₃, —NHSO₂CH₃, or —N(SO₂CH₂CH₂CH₂). In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

Further disclosed herein are siNA molecules comprising (a) a 5′-stabilized end cap of Formula (Ia):

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl, or H; R²is

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—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_n—Z, or —(C₂-C₆alkenylene)-Z and R²⁰is H; or R²and R²⁰together form a 3- to 7-membered carbocyclic ring substituted with —(CR²¹R²²)_n—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4; Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_mCO₂R²³, —OP(S)OH(CH₂)_mCO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_mP(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴, —NR²³SO₂R²⁵; either R²¹and R²²are independently hydrogen or C₁-C₆alkyl, or R²¹and R²²together form an oxo group; R²³is hydrogen or C₁-C₆alkyl; R²⁴is —SO₂R²⁵or —C(O)R²⁵; or R²³and R²⁴together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic ring; R²⁵is C₁-C₆alkyl; and m is 1, 2, 3, or 4; and (b) a short interfering nucleic acid (siNA), wherein the 5′-stabilized end cap is conjugated to the siNA. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

Further disclosed herein are siNA molecules comprising (a) a 5′-stabilized end cap of Formula (Ib):

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl, or H; R²is

embedded image

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_n—Z, or —(C₂-C₆alkenylene)-Z and R²⁰is H; or R²and R²⁰together form a 3- to 7-membered carbocyclic ring substituted with —(CR²¹R²²)_n—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4; Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_mCO₂R²³, —OP(S)OH(CH₂)_mCO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_mP(O)(OH)₂, —SO₂NR²³R²⁵, —NR²³R²⁴, —NR²³SO₂R²⁵; either R²¹and R²²are independently hydrogen or C₁-C₆alkyl, or R²¹and R²²together form an oxo group; R²³is hydrogen or C₁-C₆alkyl; R²⁴is —SO₂R²⁵or —C(O)R²⁵; or R²³and R²⁴together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic ring; R²⁵is C₁-C₆alkyl; and m is 1, 2, 3, or 4; and (b) a short interfering nucleic acid (siNA), wherein the 5′-stabilized end cap is conjugated to the siNA. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

Further disclosed herein are siNA molecules comprising (a) a 5′-stabilized end cap of Formula (Ic):

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl, or H, R²is

embedded image

—CH═CD-Z, —CD=CH—Z, —CD=CD-Z, —(CR²¹R²²)_n—Z, or —(C₂-C₆alkenylene)-Z and R²⁰is hydrogen; or R²and R²⁰together form a 3- to 7-membered carbocyclic ring substituted with —(CR²¹R²²)_n—Z or —(C₂-C₆alkenylene)-Z; n is 1, 2, 3, or 4; Z is —ONR²³R²⁴, —OP(O)OH(CH₂)_mCO₂R²³, —OP(S)OH(CH₂)_mCO₂R²³, —P(O)(OH)₂, —P(O)(OH)(OCH₃), —P(O)(OH)(OCD₃), —SO₂(CH₂)_mP(O)(OH)₂, —SO₂NR²³R²⁵, NR²³R²⁴, or —NR²³SO₂R²⁵; R²¹and R²²either are independently hydrogen or C₁-C₆alkyl, or R²¹and R²²together form an oxo group; R²³is hydrogen or C₁-C₆alkyl; R²⁴is —SO₂R²⁵or —C(O)R²⁵; or R²³and R²⁴together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic ring; R²⁵is C₁-C₆alkyl; and m is 1, 2, 3, or 4; and (b) a short interfering nucleic acid (siNA), wherein the 5′-stabilized end cap is conjugated to the siNA. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, a siNA molecule comprises (a) a 5′-stabilized end cap of Formula (IIa):

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl, or H, R²is

embedded image

CH₂SO₂NHCH₃, or

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R⁹is —SO₂CH₃or —COCH₃, wherein custom-character is a double or single bond, R¹⁰=—CH₂PO₃H or —NHCH₃, R¹¹is —CH₂— or —CO—, and R¹²is H and R¹³is CH₃or R¹²and R¹³together form —CH₂CH₂CH₂—; and (b) a short interfering nucleic acid (siNA), wherein the 5′-stabilized end cap is conjugated to the siNA. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, a siNA molecule comprises (a) a 5′-stabilized end cap of Formula (IIb):

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl, or H, R²is

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CH₂SO₂NHCH₃, or

embedded image

In some embodiments, a siNA molecule comprises (a) a 5′-stabilized end cap of Formula (III):

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl, or H, L is —CH₂—, —CH═CH—, —CO—, or —CH₂CH₂—, and A is —ONHCOCH₃, —ONHSO₂CH₃, —PO₃H, —OP(SOH)CH₂CO₂H, —SO₂CH₂PO₃H, —SO₂NHCH₃, —NHSO₂CH₃, or —N(SO₂CH₂CH₂CH₂); and (b) a siNA, wherein the 5′-stabilized end cap is conjugated to the siNA. In some embodiments, 10 is an aryl. In some embodiments, the aryl is phenyl.

In some embodiments, any of the siNA molecules disclosed herein comprise a 5′-stabilized end cap selected from the group consisting of Formula (1) to Formula (15), Formula (9X) to Formula (12X), and Formula (9Y) to Formula (12Y):

embedded image

wherein R¹is a nucleobase, aryl, heteroaryl, or H. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, any of the siNA molecules disclosed herein comprise a 5′-stabilized end cap selected from the group consisting of Formulas (1A)-(15A), Formulas (9B)-(12B), Formulas (9AX)-(12AX), Formulas (9AY)-(12AY), Formulas (9BX)-(12BX), and Formulas (9BY)-(12BY):

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In some embodiments, any of the siNA molecules disclosed herein comprise a 5′-stabilized end cap selected from the group consisting of Formula (21) to Formula (35):

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wherein R¹is a nucleobase, aryl, heteroaryl, or H. In some embodiments, R¹is an aryl. In some embodiments, the aryl is a phenyl.

In some embodiments, any of the siNA molecules disclosed herein comprise a 5′-stabilized end cap selected from the group consisting of Formulas (21A)-(35A), Formulas (29B)-(32B), Formulas (29AX)-(32AX), Formulas (29AY)-(32AY), Formulas (29BX)-(32BX), and Formulas (29BY)-(32BY):

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In some embodiments, the 5′-stabilized end cap is attached to the 5′ end of the antisense strand. In some embodiments, the 5′-stabilized end cap is attached to the 5′ end of the antisense strand via 1, 2, 3, 4, or 5 or more linkers. In some embodiments, one or more linkers are independently selected from the group consisting of a phosphodiester (p or po) linker, phosphorothioate (ps) linker, phosphoramidite (HEG) linker, triethylene glycol (TEG) linker, and/or phosphorodithioate linker.

Linkers

In some embodiments, any of the siRNAs, sense strands, first nucleotide sequences, antisense strands, and/or second nucleotide sequences disclosed herein comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or more internucleoside linkers. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more internucleoside linkers are independently selected from the group consisting of a phosphodiester (p or po) linker, phosphorothioate (ps) linker, or phosphorodithioate linker.

In some embodiments, any of the siRNAs, sense strands, first nucleotide sequences, antisense strands, and/or second nucleotide sequences disclosed herein further comprise 1, 2, 3, 4 or more linkers that attach a conjugated moiety, phosphorylation blocker, and/or 5′ end cap to the siRNA, sense strand, first nucleotide sequence, antisense strand, and/or second nucleotide sequences. In some embodiments, the 1, 2, 3, 4 or more linkers are independently selected from the group consisting of a phosphodiester (p or po) linker, phosphorothioate (ps) linker, phosphoramidite (HEG) linker, triethylene glycol (TEG) linker, and/or phosphorodithioate linker. In some embodiments, the one or more linkers are independently selected from the group consisting of p-(ps)₂, (ps)2-p-TEG-p, (ps)2-p-HEG-p, and (ps)2-p-(HEG-p)2.

Specific Embodiments

The present disclosure provides numerous siNA that can be used to treat or prevent viral infections, specifically coronavirus (e.g., SARS-CoV-2) infections, such as COVID-19. Table 3, below, provides a non-limiting list of siNA that incorporate the nucleic acid sequences, modified nucleotides, phosphorylation blockers, 5′ stabilized end caps, and/or linkers of the foregoing sections. Those of skill in the art will understand that other exemplary siNA can be constructed by combining the sequences disclosed in Table 1 (or fragments of the sequences disclosed in Table 2) with the modified nucleotides, phosphorylation blockers, 5′ stabilized end caps, and/or linkers of the foregoing sections.

TABLE 3

Exemplary siNA

SEQ

SEQ

ID

ID

Name
NO:
Sense Sequence (5′→3′)
NO:
Antisense Sequence (5′→3′)

ds-
4383
rGrCrUrCrCrUrArArUrUrArCrArCrUr
4605
rGrUrUrGrArGrUrGrUrArArUrUrArGr

siNA-

CrArArCTT

GrArGrCTT

001

ds-
4384
rGrGrArUrGrArGrGrArArGrGrCrArAr
4606
rUrArArArUrUrGrCrCrUrUrCrCrUrCr

siNA-

UrUrUrATT

ArUrCrCTT

002

ds-
4385
rCrCrGrCrUrGrGrArGrArGrCrArArCr
4607
rUrGrCrArGrUrUrGrCrUrCrUrCrCrUr

siNA-

UrGrCrATT

GrCrGrGTT

003

ds-
4386
rGrCrUrArUrGrArArArCrGrArUrArUr
4608
rGrCrCrCrArUrArUrCrGrUrUrUrCrAr

siNA-

GrGrGrCTT

UrArGrCTT

004

ds-
4387
fUpsmApsfGmCfAmGfCmAfUmUfA
4609
mCpsfApsmGfGmAfUmGfGmUfAmAf

siNA-

mCfCmAfUmCfCmUfGpsTpsT

UmGfCmUfGmCfUmATpsT

005

ds-
4388
mCpsfApsmAmCmAmCmGmGmAmC
4610
mUpsmApsfCmGmGmUfUfUfCmGmU

siNA-

mGmAmAfAmCmCmGmUmApsTpsT

fCmCmGmUmGfUmUmGTpsT

006

ds-
4389
mCpsmApsfCmGmUmCfCfAfAmCmU
4611
mGpsfCpsmAmAmAmCmUmGmAmG

siNA-

fCmAmGmUmUfUmGmCTpsT

mUmUmGfGmAmCmGmUmGpsTpsT

007

ds-
4390
mUpsmGpsfAmAmCmAfGfCfCmCm
4612
mGpsfApsmAmCmAmCmAmUmAmG

siNA-

UfAmUmGmUmGfUmUmCTpsT

mGmGmCfUmGmUmUmCmApsTpsT

008

ds-
4391
mApsmCpsfGmAmGmCfUfUfGmGm
4613
mGpsfGpsmAmUmCmAmGmUmGmC

siNA-

CfAmCmUmGmAfUmCmCTpsT

mCmAmAfGmCmUmCmGmUpsTpsT

009

ds-
4392
mUpsmCpsfAmUmGmUfGfGfUmAm
4614
mApsfApsmCmCmAmAmCmAmCmU

siNA-

GfUmGmUmUmGfGmUmUTpsT

mAmCmCfAmCmAmUmGmApsTpsT

010

ds-
4393
mApsmCpsfAmAmCmAfUfUfAmUm
4615
mGpsfCpsmAmUmUmGmUmUmGmA

siNA-

CfAmAmCmAmAfUmGmCTpsT

mUmAmAfUmGmUmUmGmUpsTpsT

011

ds-
4394
mApsfApsmAmCmCmUmAmCmAmA
4616
mGpsmGpsfAmAmCmCfAfCfCmUmU

siNA-

mGmGmUfGmGmUmUmCmCpsTpsT

fGmUmAmGmGfUmUmUTpsT

012

ds-
4395
mCpsmGpsfUmUmUmUfUfAfAmAm
4617
mGpsfCpsmAmAmAmCmCmCmGmU

siNA-

CfGmGmGmUmUfUmGmCTpsT

mUmUmAfAmAmAmAmCmGpsTpsT

013

ds-
4396
mGpsfUpsmGmCmCmGmCmAmCmG
4618
mGpsmUpsfCmUmUmAfCfAfCmCmG

siNA-

mGmUmGfUmAmAmGmAmCpsTpsT

fUmGmCmGmGfCmAmCTpsT

014

ds-
4397
TmUpsfGpsmAmCmGmUmGmAmUm
4619
mUpsmApsfCmCmAmCfAfUfAmUmA

siNA-

AmUmAmUfGmUmGmGmUmApsTps

fUmCmAmCmGfUmCmATpsT

015

ds-
4398
mGpsmGpsfAmUmGmUfAfAfAmCm
4620
mGpsfCpsmUmAmUmGmUmAmAmG

siNA-

UfUmAmCmAmUfAmGmCTpsT

mUmUmUfAmCmAmUmCmCpsTpsT

016

ds-
4399
mApsfCpsmCmGmGmGmUmUmUmG
4621
mUpsmCpsfAmAmAmCfUfGfUmCmA

siNA-

mAmCmAfGmUmUmUmGmApsTpsT

fAmAmCmCmCfGmGmUTpsT

017

ds-
4400
mUpsmGpsfUmCmAmAfAfCfCmCm
4622
mApsfApsmAmAmUmUmAmCmCmG

siNA-

GfGmUmAmAmUfUmUmUTpsT

mGmGmUfUmUmGmAmCmApsTpsT

018

ds-
4401
mUpsmApsfAmGmUmAfUfGfCmCm
4623
mUpsfGpsmCmAmCmUmAmAmUmG

siNA-

AfUmUmAmGmUfGmCmATpsT

mGmCmAfUmAmCmUmUmApsTpsT

019

ds-
4402
mUpsmGpsfCmCmAmUfUfAfGmUm
4624
mApsfUpsmUmCmUmUmUmGmCmA

siNA-

GfCmAmAmAmGfAmAmUTpsT

mCmUmAfAmUmGmGmCmApsTpsT

020

ds-
4403
mGpsfCpsmGmAmGmCmUmCmUmA
4625
mUpsmGpsfCmAmAmAfGfAfAmUmA

siNA-

mUmUmCfUmUmUmGmCmApsTpsT

fGmAmGmCmUfCmGmCTpsT

021

ds-
4404
mGpsfApsmCmAmCmCmAmGmCmU
4626
mUpsmCpsfGmCmAmCfCfGfUmAmG

siNA-

mAmCmGfGmUmGmCmGmApsTpsT

fCmUmGmGmUfGmUmCTpsT

022

ds-
4405
mCpsmApsfAmUmAmGfCfCfGmCmC
4627
mCpsfCpsmUmCmUmAmGmUmGmG

siNA-

fAmCmUmAmGfAmGmGTpsT

mCmGmGfCmUmAmUmUmGpsTpsT

023

ds-
4406
mApsmCpsfUmGmCmUfUfAfUmGm
4628
mCpsfApsmCmUmAmUmUmAmGmC

siNA-

CfUmAmAmUmAfGmUmGTpsT

mAmUmAfAmGmCmAmGmUpsTpsT

024

ds-
4407
mApsfCpsmAmUmCmAmGmCmAmU
4629
mApsmUpsfCmAmGmGfAfGfUmAmU

siNA-

mAmCmUfCmCmUmGmAmUpsTpsT

fGmCmUmGmAfUmGmUTpsT

025

ds-
4408
mUpsmApsfGmGmAmGfGfUfAmUm
4630
mUpsfApsmAmUmAmGmCmUmCmA

siNA-

GfAmGmCmUmAfUmUmATpsT

mUmAmCfCmUmCmCmUmApsTpsT

026

ds-
4409
mApsmCpsfUmAmUmGfGfUfGmAm
4631
mApsfCpsmAmAmCmAmGmCmAmU

siNA-

UfGmCmUmGmUfUmGmUTpsT

mCmAmCfCmAmUmAmGmUpsTpsT

027

ds-
4410
mApsfCpsmAmUmAmGmUmGmCmU
4632
mUpsmGpsfCmCmAmCfAfAfGmAmG

siNA-

mCmUmUfGmUmGmGmCmApsTpsT

fCmAmCmUmAfUmGmUTpsT

028

ds-
4411
mUpsfApsmUmAmCmAmCmUmAmU
4633
mUpsmCpsfUmGmCmUfCfGfCmAmU

siNA-

mGmCmGfAmGmCmAmGmApsTpsT

fAmGmUmGmUfAmUmATpsT

029

ds-
4412
mApsmApsfUmUmCmAfAfAfGmUm
4634
mGpsfUpsmUmGmAmAmUmUmCmA

siNA-

GfAmAmUmUmCfAmAmCTpsT

mCmUmUfUmGmAmAmUmUpsTpsT

030

ds-
4413
mApsfGpsmGmAmAmCmAmUmGm
4635
mUpsmApsfGmGmUmCfCfAfGmAmC

siNA-

UmCmUmGfGmAmCmCmUmApsTps

fAmUmGmUmUfCmCmUTpsT

031

T

ds-
4414
mUpsfGpsmAmAmUmAmUmGmAm
4636
mUpsmApsfUmGmAmCfUfAfUmGmU

siNA-

CmAmUmAfGmUmCmAmUmApsTps

fCmAmUmAmUfUmCmATpsT

032

T

ds-
4415
mUpsmUpsfUmGmAmGfCfUfUmUm
4637
mGpsfCpsmUmUmAmGmCmCmCmA

siNA-

GfGmGmCmUmAfAmGmCTpsT

mAmAmGfCmUmCmAmAmApsTpsT

033

ds-
4416
mUpsmApsfAmUmGmAfUfGfAmAm
4638
mUpsfUpsmUmGmCmGmAmCmAmU

siNA-

UfGmUmCmGmCfAmAmATpsT

mUmCmAfUmCmAmUmUmApsTpsT

034

ds-
4417
mGpsmApsfGmUmAmCfGfAfAmCm
4639
mApsfGpsmUmAmCmAmUmAmAmG

siNA-

UfUmAmUmGmUfAmCmUTpsT

mUmUmCfGmUmAmCmUmCpsTpsT

035

ds-
4418
mGpsmGpsfUmAmCmGfUfUfAmAm
4640
mUpsfApsmUmUmAmAmCmUmAmU

siNA-

UfAmGmUmUmAfAmUmATpsT

mUmAmAfCmGmUmAmCmCpsTpsT

036

ds-
4419
mGpsfApsmAmAmAmAmGmAmAm
4641
mApsmApsfUmAmGmCfGfUfAmCmU

siNA-

GmUmAmCfGmCmUmAmUmUpsTps

fUmCmUmUmUfUmUmCTpsT

037

T

ds-
4420
mGpsfCpsmAmAmGmAmAmUmAmC
4642
mGpsmCpsfUmUmUmCfGfUfGmGmU

siNA-

mCmAmCfGmAmAmAmGmCpsTpsT

fAmUmUmCmUfUmGmCTpsT

038

ds-
4421
mApsfCpsmAmAmUmCmGmAmAmG
4643
mCpsmUpsfUmAmCmUfGfCfGmCmU

siNA-

mCmGmCfAmGmUmAmAmGpsTpsT

fUmCmGmAmUfUmGmUTpsT

039

ds-
4422
mUpsmUpsfCmUmGmGfUfCfUmAm
4644
mUpsfApsmGmUmUmCmGmUmUmU

siNA-

AfAmCmGmAmAfCmUmATpsT

mAmGmAfCmCmAmGmAmApsTpsT

040

ds-
4423
mUpsfApsmAmUmAmAmGmAmAm
4645
mCpsmApsfCmGmAmAfCfGfCmUmU

siNA-

AmGmCmGfUmUmCmGmUmGpsTps

fUmCmUmUmAfUmUmATpsT

041

T

ds-
4424
mUpsfGpsmUmAmUmGmCmAmGmC
4646
mUpsmCpsfAmGmGmUfUfUfUmGmC

siNA-

mAmAmAfAmCmCmUmGmApsTpsT

fUmGmCmAmUfAmCmATpsT

042

ds-
4425
mCpsfApsmUmCmUmGmUmUmGmU
4647
mCpsmApsfGmUmAmAfGfUfGmAmC

siNA-

mCmAmCfUmUmAmCmUmGpsTpsT

fAmAmCmAmGfAmUmGTpsT

043

ds-
4426
mUpsmApsfCmCmCmAfAfUfAmAm
4648
mGpsfApsmCmGmCmAmGmUmAmU

siNA-

UfAmCmUmGmCfGmUmCTpsT

mUmAmUfUmGmGmGmUmApsTpsT

044

ds-
4427
mCpsfUpsmUmCmGmGmUmAmGmU
4649
mApsmApsfAmUmUmGfGfCfUmAmC

siNA-

mAmGmCfCmAmAmUmUmUpsTpsT

fUmAmCmCmGfAmAmGTpsT

045

ds-
4428
mCpsmApsfAmAmAmGfGfCfUmUm
4650
mUpsfCpsmUmGmCmGmUmAmGmA

siNA-

CfUmAmCmGmCfAmGmATpsT

mAmGmCfCmUmUmUmUmGpsTpsT

046

ds-
4429
mUpsmGpsfUmCmAmCfUfAfAmGm
4651
mApsfGpsmCmAmGmAmUmUmUmC

siNA-

AfAmAmUmCmUfGmCmUTpsT

mUmUmAfGmUmGmAmCmApsTpsT

047

ds-
4430
mGpsmApsfCmAmAmGfGfAfAmCm
4652
mUpsfUpsmGmUmAmAmUmCmAmG

siNA-

UfGmAmUmUmAfCmAmATpsT

mUmUmCfCmUmUmGmUmCpsTpsT

048

ds-
4431
mCpsmApsfUmGmGmAfAfGfUmCm
4653
mCpsfGpsmAmAmGmGmUmGmUmG

siNA-

AfCmAmCmCmUfUmCmGTpsT

mAmCmUfUmCmCmAmUmGpsTpsT

049

ds-
4432
mCpsfApsmUmUmCmUmGmCmAmC
4654
mUpsmCpsfUmAmCmUfCfUfUmGmU

siNA-

mAmAmGfAmGmUmAmGmApsTpsT

fGmCmAmGmAfAmUmGTpsT

050

ds-
4433
mCpsmApsfCmAmUmAfGfCfAmAm
4655
mGpsfApsmUmUmAmAmAmGmAmU

siNA-

UfCmUmUmUmAfAmUmCTpsT

mUmGmCfUmAmUmGmUmGpsTpsT

051

ds-
4434
mApsfApsmAmUmGmUmGmGmUm
4656
mUpsmGpsfAmAmAmGfAfGfCmCmA

siNA-

GmGmCmUfCmUmUmUmCmApsTps

fCmCmAmCmAfUmUmUTpsT

052

T

ds-
4435
mUpsfUpsmUmAmCmAmCmAmUmU
4657
mApsmApsfGmAmGmCfCfCfUmAmA

siNA-

mAmGmGfGmCmUmCmUmUpsTpsT

fUmGmUmGmUfAmAmATpsT

053

ds-
4436
mUpsmApsmCmGfGmUmUmUfCfGf
4658
mUpsfGpsmCmAmAmCmAmCmGmG

siNA-

UmCmCfGmUmGmUmUfGmCpsmA

mAmCmGfAmAmAmCmCmGmUmAp

054

sTpsT

ds-
4437
mApsfApsmCmUmGmAmGmUmUm
4659
mApsmApsmAmCfAmCmAmCfGfUfC

siNA-

GmGmAmCfGmUmGmUmGmUmUm

mCmAfAmCmUmCmAfGmUpsmU

055

UpsTpsT

ds-
4438
mUpsmGpsmAmAfCmAmGmCfCfCf
4660
mApsfUpsmGmAmAmCmAmCmAmU

siNA-

UmAmUfGmUmGmUmUfCmApsmU

mAmGmGfGmCmUmGmUmUmCmAp

056

sTpsT

ds-
4439
mUpsmApsmUmUfUmAmAmAfAfCf
4661
mApsfUpsmUmGmUmCmAmGmUmA

siNA-

UmUmAfCmUmGmAmCfAmApsmU

mAmGmUfUmUmUmAmAmAmUmA

057

psTpsT

ds-
4440
mUpsfUpsmUmUmCmCmAmCmUmA
4662
mCpsmUpsmCmUfGmAmAmGfAfAfG

siNA-

mCmUmUfCmUmUmCmAmGmAmG

mUmAfGmUmGmGmAfAmApsmA

058

psTpsT

ds-
4441
mUpsfGpsmUmUmAmAmAmAmCmC
4663
mGpsmUpsmGmGfUmAmGmUfGfUf

siNA-

mAmAmCfAmCmUmAmCmCmAmC

UmGmGfUmUmUmUmAfAmCpsmA

059

psTpsT

ds-
4442
mGpsfUpsmAmAmCmAmAmAmCmC
4664
mApsmCpsmCmAfCmCmUmUfGfUfA

siNA-

mUmAmCfAmAmGmGmUmGmGmU

mGmGfUmUmUmGmUfUmApsmC

060

psTpsT

ds-
4443
mUpsmGpsmUmUfGmUmGmUfAfCf
4665
mUpsfApsmCmCmAmGmUmGmUmG

siNA-

AmCmAfCmAmCmUmGfGmUpsmA

mUmGmUfAmCmAmCmAmAmCmAp

061

sTpsT

ds-
4444
mApsmApsmAmGfGmUmUmAfUfGf
4666
mApsfCpsmAmAmCmUmAmCmAmG

siNA-

GmCmUfGmUmAmGmUfUmGpsmU

mCmCmAfUmAmAmCmCmUmUmUp

062

sTpsT

ds-
4445
mUpsfUpsmAmCmAmCmCmGmCmA
4667
mUpsmUpsmAmAfAmCmGmGfGfUfU

siNA-

mAmAmCfCmCmGmUmUmUmAmA

mUmGfCmGmGmUmGfUmApsmA

063

psTpsT

ds-
4446
mGpsmUpsmGmUfAmAmGmUfGfCf
4668
mUpsfApsmAmGmAmCmGmGmGmC

siNA-

AmGmCfCmCmGmUmCfUmUpsmA

mUmGmCfAmCmUmUmAmCmAmCp

064

sTpsT

ds-
4447
mApsmCpsmAmUfGmGmUmAfCfCf
4669
mGpsfUpsmGmAmUmAmUmAmUmG

siNA-

AmCmAfUmAmUmAmUfCmApsmC

mUmGmGfUmAmCmCmAmUmGmUp

065

sTpsT

ds-
4448
mUpsfUpsmAmCmCmGmGmGmUmU
4670
mUpsmCpsmAmAfAmCmUmGfUfCfA

siNA-

mUmGmAfCmAmGmUmUmUmGmA

mAmAfCmCmCmGmGfUmApsmA

066

psTpsT

ds-
4449
mUpsfGpsmAmGmCmAmAmAmGm
4671
mApsmApsmAmAfCmAmCmUfUfCfU

siNA-

AmAmGmAfAmGmUmGmUmUmUm

mUmCfUmUmUmGmCfUmCpsmA

067

UpsTpsT

ds-
4450
mApsfGpsmCmCmAmCmCmAmUmC
4672
mUpsmUpsmGmAfUmUmGmUfUfAfC

siNA-

mGmUmAfAmCmAmAmUmCmAmA

mGmAfUmGmGmUmGfGmCpsmU

068

psTpsT

ds-
4451
mApsmApsmAmUfGmAmAmUfCfUf
4673
mUpsfGpsmGmCmAmUmAmCmUmU

siNA-

UmAmAfGmUmAmUmGfCmCpsmA

mAmAmGfAmUmUmCmAmUmUmU

069

psTpsT

ds-
4452
mApsfUpsmUmCmUmUmUmGmCmA
4674
mUpsmApsmUmGfCmCmAmUfUfAfG

siNA-

mCmUmAfAmUmGmGmCmAmUmA

mUmGfCmAmAmAmGfAmApsmU

070

psTpsT

ds-
4453
mCpsfUpsmAmUmUmCmUmUmUmG
4675
mUpsmGpsmCmCfAmUmUmAfGfUfG

siNA-

mCmAmCfUmAmAmUmGmGmCmA

mCmAfAmAmGmAmAfUmApsmG

071

psTpsT

ds-
4454
mCpsfUpsmAmCmGmGmUmGmCmG
4676
mApsmGpsmAmAfUmAmGmAfGfCfU

siNA-

mAmGmCfUmCmUmAmUmUmCmU

mCmGfCmAmCmCmGfUmApsmG

072

psTpsT

ds-
4455
mApsmUpsmAmGfAmGmCmUfCfGf
4677
mCpsfApsmGmCmUmAmCmGmGmU

siNA-

CmAmCfCmGmUmAmGfCmUpsmG

mGmCmGfAmGmCmUmCmUmAmUp

073

sTpsT

ds-
4456
mUpsmCpsmGmCfAmCmCmGfUfAf
4678
mGpsfApsmGmAmCmAmCmCmAmG

siNA-

GmCmUfGmGmUmGmUfCmUpsmC

mCmUmAfCmGmGmUmGmCmGmAp

074

sTpsT

ds-
4457
mApsmApsmCmUfGmCmUmUfAfUf
4679
mApsfCpsmAmCmUmAmUmUmAmG

siNA-

GmCmUfAmAmUmAmGfUmGpsmU

mCmAmUfAmAmGmCmAmGmUmUp

075

sTpsT

ds-
4458
mUpsfUpsmAmGmUmAmAmGmGm
4680
mGpsmApsmCmUfGmAmGmAfCfUfG

siNA-

UmCmAmGfUmCmUmCmAmGmUm

mAmCfCmUmUmAmCfUmApsmA

076

CpsTpsT

ds-
4459
mApsfCpsmCmUmUmUmUmUmCmA
4681
mGpsmApsmGmUfAmCmAmCfCfUfU

siNA-

mAmAmGfGmUmGmUmAmCmUmC

mUmGfAmAmAmAmAfGmGpsmU

077

psTpsT

ds-
4460
mUpsmGpsmGmUfAmCmUmGfGfUf
4682
mApsfApsmAmUmGmAmCmUmCmU

siNA-

AmAmGfAmGmUmCmAfUmUpsmU

mUmAmCfCmAmGmUmAmCmCmAp

078

sTpsT

ds-
4461
mUpsmCpsmUmGfCmUmAmAfUfCf
4683
mApsfGpsmUmAmGmCmAmGmCmA

siNA-

UmUmGfCmUmGmCmUfAmCpsmU

mAmGmAfUmUmAmGmCmAmGmA

079

psTpsT

ds-
4462
mCpsfGpsmCmUmAmUmUmAmAmC
4684
mGpsmUpsmAmCfGmUmUmAfAfUfA

siNA-

mUmAmUfUmAmAmCmGmUmAmC

mGmUfUmAmAmUmAfGmCpsmG

080

psTpsT

ds-
4463
mUpsmUpsmCmUfUmGmCmUfUfUf
4685
mApsfGpsmAmAmUmAmCmCmAmC

siNA-

CmGmUfGmGmUmAmUfUmCpsmU

mGmAmAfAmGmCmAmAmGmAmA

081

psTpsT

ds-
4464
mCpsmUpsmUmAfCmUmGmCfGfCf
4686
mApsfCpsmAmCmAmAmUmCmGmA

siNA-

UmUmCfGmAmUmUmGfUmGpsmU

mAmGmCfGmCmAmGmUmAmAmGp

082

sTpsT

ds-
4465
mCpsmGpsmCmUfUmCmGmAfUfUf
4687
mApsfGpsmUmAmCmGmCmAmCmA

siNA-

GmUmGfUmGmCmGmUfAmCpsmU

mCmAmAfUmCmGmAmAmGmCmGp

083

sTpsT

ds-
4466
mUpsfApsmAmCmAmAmUmAmUm
4688
mCpsmGpsmUmAfCmUmGmCfUfGfC

siNA-

UmGmCmAfGmCmAmGmUmAmCm

mAmAfUmAmUmUmGfUmUpsmA

084

GpsTpsT

ds-
4467
mUpsfCpsmGmUmUmUmAmGmAmC
4689
mCpsmUpsmGmAfUmCmUmUfCfUfG

siNA-

mCmAmGfAmAmGmAmUmCmAmG

mGmUfCmUmAmAmAfCmGpsmA

085

psTpsT

ds-
4468
mUpsmCpsmAmCfGmAmAmCfGfCf
4690
mGpsfUpsmAmAmUmAmAmGmAmA

siNA-

UmUmUfCmUmUmAmUfUmApsmC

mAmGmCfGmUmUmCmGmUmGmAp

086

sTpsT

ds-
4469
mUpsmApsmAmAfCmGmAmAfCfAf
4691
mApsfApsmUmAmAmUmUmUmUmC

siNA-

UmGmAfAmAmAmUmUfAmUpsmU

mAmUmGfUmUmCmGmUmUmUmA

087

psTpsT

ds-
4470
mApsmApsmUmUfGmAmCmUfUfCf
4692
mApsfApsmGmCmAmCmAmAmAmU

siNA-

UmAmUfUmUmGmUmGfCmUpsmU

mAmGmAfAmGmUmCmAmAmUmU

088

psTpsT

ds-
4471
mCpsmApsmAmUfAmAmUmAfCfUf
4693
mApsfApsmCmCmAmAmGmAmCmG

siNA-

GmCmGfUmCmUmUmGfGmUpsmU

mCmAmGfUmAmUmUmAmUmUmG

089

psTpsT

ds-
4472
mApsmUpsmUmGfGmCmUmAfCfUf
4694
mApsfGpsmCmUmCmUmUmCmGmG

siNA-

AmCmCfGmAmAmGmAfGmCpsmU

mUmAmGfUmAmGmCmCmAmAmUp

090

sTpsT

ds-
4473
mCpsfCpsmUmUmGmAmGmGmAmA
4695
mCpsmGpsmUmGfCmUmAmCfAfAfC

siNA-

mGmUmUfGmUmAmGmCmAmCmG

mUmUfCmCmUmCmAfAmGpsmG

091

psTpsT

ds-
4474
mUpsfGpsmCmUmCmUmCmAmAmG
4696
mGpsmApsmUmUfGmAmAmCfCfAfG

siNA-

mCmUmGfGmUmUmCmAmAmUmC

mCmUfUmGmAmGmAfGmCpsmA

092

psTpsT

ds-
4475
mUpsmGpsmGmUfAmAmAmGfGfCf
4697
mUpsfGpsmUmUmGmUmUmGmUmU

siNA-

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ds-
4555
fUpsmGpsfGmUfAmCfUmGfGmUfA
4777
mApsfApsmAfUmGfAmCfUmCfUmUf

siNA-

mAfGmAfGmUfCmAfUmUpsfU

AmCfCmAfGmUfAmCfCmApsTpsT

173

ds-
4556
fUpsmCpsfUmGfCmUfAmAfUmCfUm
4778
mApsfGpsmUfAmGfCmAfGmCfAmAf

siNA-

UfGmCfUmGfCmUfAmCpsfU

GmAfUmUfAmGfCmAfGmApsTpsT

174

ds-
4557
fGpsmUpsfAmCfGmUfUmAfAmUfA
4779
mCpsfGpsmCfUmAfUmUfAmAfCmUf

siNA-

mGfUmUfAmAfUmAfGmCpsfG

AmUfUmAfAmCfGmUfAmCpsTpsT

175

ds-
4558
fUpsmUpsfCmUfUmGfCmUfUmUfCm
4780
mApsfGpsmAfAmUfAmCfCmAfCmGf

siNA-

GfUmGfGmUfAmUfUmCpsfU

AmAfAmGfCmAfAmGfAmApsTpsT

176

ds-
4559
fCpsmUpsfUmAfCmUfGmCfGmCfUm
4781
mApsfCpsmAfCmAfAmUfCmGfAmAf

siNA-

UfCmGfAmUfUmGfUmGpsfU

GmCfGmCfAmGfUmAfAmGpsTpsT

177

ds-
4560
fCpsmGpsfCmUfUmCfGmAfUmUfGm
4782
mApsfGpsmUfAmCfGmCfAmCfAmCf

siNA-

UfGmUfGmCfGmUfAmCpsfU

AmAfUmCfGmAfAmGfCmGpsTpsT

178

ds-
4561
fCpsmGpsfUmAfCmUfGmCfUmGfCm
4783
mUpsfApsmAfCmAfAmUfAmUfUmGf

siNA-

AfAmUfAmUfUmGfUmUpsfA

CmAfGmCfAmGfUmAfCmGpsTpsT

179

ds-
4562
mUpsfCpsmGfUmUfUmAfGmAfCmCf
4784
fCpsmUpsfGmAfUmCfUmUfCmUfGm

siNA-

AmGfAmAfGmAfUmCfAmGpsTpsT

GfUmCfUmAfAmAfCmGpsfA

180

ds-
4563
mGpsfUpsmAfAmUfAmAfGmAfAmA
4785
fUpsmCpsfAmCfGmAfAmCfGmCfUm

siNA-

fGmCfGmUfUmCfGmUfGmApsTpsT

UfUmCfUmUfAmUfUmApsfC

181

ds-
4564
mApsfApsmUfAmAfUmUfUmUfCmA
4786
fUpsmApsfAmAfCmGfAmAfCmAfUm

siNA-

fUmGfUmUfCmGfUmUfUmApsTpsT

GfAmAfAmAfUmUfAmUpsfU

182

ds-
4565
mApsfApsmGfCmAfCmAfAmAfUmA
4787
fApsmApsfUmUfGmAfCmUfUmCfUm

siNA-

fGmAfAmGfUmCfAmAfUmUpsTpsT

AfUmUfUmGfUmGfCmUpsfU

183

ds-
4566
mApsfApsmCfCmAfAmGfAmCfGmCf
4788
fCpsmApsfAmUfAmAfUmAfCmUfGm

siNA-

AmGfUmAfUmUfAmUfUmGpsTpsT

CfGmUfCmUfUmGfGmUpsfU

184

ds-
4567
fApsmUpsfUmGfGmCfUmAfCmUfA
4789
mApsfGpsmCfUmCfUmUfCmGfGmUf

siNA-

mCfCmGfAmAfGmAfGmCpsfU

AmGfUmAfGmCfCmAfAmUpsTpsT

185

ds-
4568
fCpsmGpsfUmGfCmUfAmCfAmAfCm
4790
mCpsfCpsmUfUmGfAmGfGmAfAmGf

siNA-

UfUmCfCmUfCmAfAmGpsfG

UmUfGmUfAmGfCmAfCmGpsTpsT

186

ds-
4569
fGpsmApsfUmUfGmAfAmCfCmAfG
4791
mUpsfGpsmCfUmCfUmCfAmAfGmCf

siNA-

mCfUmUfGmAfGmAfGmCpsfA

UmGfGmUfUmCfAmAfUmCpsTpsT

187

ds-
4570
fUpsmGpsfGmUfAmAfAmGfGmCfC
4792
mUpsfGpsmUfUmGfUmUfGmUfUmGf

siNA-

mAfAmCfAmAfCmAfAmCpsfA

GmCfCmUfUmUfAmCfCmApsTpsT

188

ds-
4571
mGpsfCpsmCfUmCfAmGfCmAfGmCf
4793
fUpsmApsfAmGfAmAfAmUfCmUfGm

siNA-

AmGfAmUfUmUfCmUfUmApsTpsT

CfUmGfCmUfGmAfGmGpsfC

189

ds-
4572
fApsmGpsfAmCfAmAfGmGfAmAfC
4794
mUpsfUpsmUfGmUfAmAfUmCfAmGf

siNA-

mUfGmAfUmUfAmCfAmApsfA

UmUfCmCfUmUfGmUfCmUpsTpsT

190

ds-
4573
fApsmApsfAmUfUmGfGmAfUmGfA
4795
mUpsfGpsmGfAmUfCmUfUmUfGmUf

siNA-

mCfAmAfAmGfAmUfCmCpsfA

CmAfUmCfCmAfAmUfUmUpsTpsT

191

ds-
4574
fCpsmApsfCmCfAmAfCmAfGmAfGm
4796
mCpsfCpsmUfUmUfUmUfAmGfGmCf

siNA-

CfCmUfAmAfAmAfAmGpsfG

UmCfUmGfUmUfGmGfUmGpsTpsT

192

ds-
4575
mApsfUpsmUfCmAfUmUfCmUfGmCf
4797
fCpsmUpsfAmCfUmCfUmUfGmUfGm

siNA-

AmCfAmAfGmAfGmUfAmGpsTpsT

CfAmGfAmAfUmGfAmApsfU

193

ds-
4576
mUpsfCpsmGfAmUfCmGfUmAfCmUf
4798
fGpsmGpsfCmCfAmCfGmCfGmGfAm

siNA-

CmCfGmCfGmUfGmGfCmCpsTpsT

GfUmAfCmGfAmUfCmGpsfA

194

ds-
4577
mUpsfUpsmUfUmAfCmAfCmAfUmU
4799
fGpsmApsfAmGfAmGfCmCfCmUfAm

siNA-

fAmGfGmGfCmUfCmUfUmCpsTpsT

AfUmGfUmGfUmAfAmApsfA

195

ds-
4578
mApsmGpsmAmCfAmAmGmGfAfAf
4800
vmUpsfUpsmUmGmUmAmAmUmCm

siNA-

CmUmGfAmUmUmAmCfAmApsmA

AmGmUmUfCmCmUmUmGmUmCm

196

UpsTpsT

ds-
4579
fApsmApsfCmUfGmCfUmUfAmUfG
4801
vmApsfCpsmAfCmUfAmUfUmAfGmC

siNA-

mCfUmAfAmUfAmGfUmGpsfU

fAmUfAmAfGmCfAmGfUmUpsTpsT

197

ds-
4580
fUpsmUpsfCmUfUmGfCmUfUmUfCm
4802
vmApsfGpsmAfAmUfAmCfCmAfCmG

siNA-

GfUmGfGmUfAmUfUmCpsfU

fAmAfAmGfCmAfAmGfAmApsTpsT

198

ds-
4581
fCpsmUpsfAmCfUmCfUmUfGmUfGm
4803
vmApsfUpsmUfCmAfUmUfCmUfGmC

siNA-

CfAmGfAmAfUmGfAmApsfU

fAmCfAmAfGmAfGmUfAmGpsTpsT

199

ds-
4582
fUpsmUpsfGmAfAmGfGmUfGmUfC
4804
mCpsfApsmAfAmCfAmGfAmGfAmCf

siNA-

mUfCmUfGmUfUmUfGTpsT

AmCfCmUfUmCfAmApsTpsT

200

ds-
4583
mApsfApsmGfUmCfAmAfCmAfCmCf
4805
fUpsmUpsfGmUfUmAfAmUfGmGfUm

siNA-

AmUfUmAfAmCfAmApsTpsT

GfUmUfGmAfCmUfUTpsT

201

ds-
4584
mUpsfCpsmAfAmCfUmGfUmUfGmCf
4806
fUpsmUpsfAmCfUmUfUmUfGmCfAm

siNA-

AmAfAmAfGmUfAmApsTpsT

AfCmAfGmUfUmGfATpsT

202

ds-
4585
mUpsfCpsmAfUmAfAmCfAmAfAmCf
4807
fApsmUpsfGmCfUmGfGmUfGmUfUm

siNA-

AmCfCmAfGmCfAmUpsTpsT

UfGmUfUmAfUmGfATpsT

203

ds-
4586
mGpsfUpsmAfGmUfUmGfCmAfUmC
4808
fCpsmUpsfUmCfUmGfGmUfGmAfUm

siNA-

fAmCfCmAfGmAfAmGpsTpsT

GfCmAfAmCfUmAfCTpsT

204

ds-
4587
fUpsmGpsfCmUfCmAfCmAfGmCfAm
4809
mGpsfCpsmAfUmAfGmUfGmUfGmCf

siNA-

CfAmCfUmAfUmGfCTpsT

UmGfUmGfAmGfCmApsTpsT

205

ds-
4588
fApsmGpsfAmUfGmCfGmGfUmGfA
4810
mGpsfUpsmAfAmAfCmAfAmUfCmAf

siNA-

mUfUmGfUmUfUmAfCTpsT

CmCfGmCfAmUfCmUpsTpsT

206

ds-
4589
mApsfUpsmCfUmAfCmUfUmUfCmUf
4811
fUpsmGpsfUmGfUmUfUmGfAmGfAm

siNA-

CmAfAmAfCmAfCmApsTpsT

AfAmGfUmAfGmAfUTpsT

207

ds-
4590
fUpsmUpsfUmAfAmUfGmUfUmAfG
4812
mApsfApsmGfCmAfUmCfAmCfUmAf

siNA-

mUfGmAfUmGfCmUfUTpsT

AmCfAmUfUmAfAmApsTpsT

208

ds-
4591
fApsmCpsfUmAfAmAfCmUfUmCfCm
4813
mCpsfGpsmUfAmAfUmAfAmGfGmAf

siNA-

UfUmAfUmUfAmCfGTpsT

AmGfUmUfUmAfGmUpsTpsT

209

ds-
4592
mUpsfUpsmUfGmUfAmAfUmCfAmG
4814
fApsmGpsfAmCfAmAfGmGfAmAfCm

siNA-

fUmUfCmCfUmUfGmUfCmUpsTpsT

UfGmAfUmUfAmCfAmAfATpsT

210

ds-
4593
fCpsmUpsfUmAfCmUfGmCfGmCfUm
4815
mApsfCpsmAfAmUfCmGfAmAfGmCf

siNA-

UfCmGfAmUfUmGfUTpsT

GmCfAmGfUmAfAmGpsTpsT

211

ds-
4594
mApsfCpsmAfCmUfAmUfUmAfGmCf
4816
fApsmApsfCmUfGmCfUmUfAmUfGm

siNA-

AmUfAmAfGmCfAmGfUmUpsTpsT

CfUmAfAmUfAmGfUmGfUTpsT

212

ds-
4595
mApsfGpsmAfAmUfAmCfCmAfCmGf
4817
fUpsmUpsfCmUfUmGfCmUfUmUfCm

siNA-

AmAfAmGfCmAfAmGfAmApsTpsT

GfUmGfGmUfAmUfUmCfUTpsT

213

ds-
4596
mApsfCpsmAfCmAfAmUfCmGfAmAf
4818
fCpsmUpsfUmAfCmUfGmCfGmCfUm

siNA-

GmCfGmCfAmGfUmAfAmGpsTpsT

UfCmGfAmUfUmGfUmGfUTpsT

214

ds-
4597
fCpsmUpsfAmCfUmCfUmUfGmUfGm
4819
mApsfUpsmUfCmAfUmUfCmUfGmCf

siNA-

CfAmGfAmAfUmGfAmAfUTpsT

AmCfAmAfGmAfGmUfAmGpsTpsT

215

ds-
4598
fUpsmUpsfUmCfUmCfAmAfCmUfAm
4820
mApsfGpsmGfAmAfGmUfUmUfAmGf

siNA-

AfAmCfUmUfCmCfUpsTpsT

UmUfGmAfGmAfAmApsTpsT

216

ds-
4599
mApsmGpsmAmCfAmAmGmGfAfAf
4821
vmUpsfUpsmUmGmUmAmAmUmCm

siNA-

CmUmGfAmUmUmAmCfAmAmA

AmGmUmUfCmCmUmUmGmUmCm

217

UpsTpsT

ds-
4600
mApsmGpsmAmCmAmAfGmGfAfAf
4822
vmUpsfUpsmUmGmUfAmAmUmCmA

siNA-

CmUmGmAmUmUmAmCmAmAmA

mGmUmUfCmCfUmUmGmUmCmUps

218

mUpsmU

ds-
4601
mApsmGpsmAmCmAmAfGmGfAfAf
4823
vmUpsfUpsmUmGfUmAmAfUmCmA

siNA-

CmUmGmAmUmUmAmCmAmAmA

mGmUmUfCmCmUfUmGmUfCmUps

219

mUpsmU

ds-
4602
fCpsmUpsfAmCfUmCfUmUfGmUfGm
4824
vmApsfUpsmUfCmAfUmUfCmUfGmC

siNA-

CfAmGfAmAfUmGfAmAfU

fAmCfAmAfGmAfGmUfAmGpsTpsT

220

ds-
4603
mCpsmUpsmAmCmUmCfUmUfGfUf
4825
vmApsfUpsmUmCmAfUmUmCmUmG

siNA-

GmCmAmGmAmAmUmGmAmAmU

mCmAmCfAmAfGmAmGmUmAmGps

221

mUpsmU

ds-
4604
mCpsmUpsmAmCmUmCfUmUfGfUf
4826
vmApsfUpsmUmCfAmUmUfCmUmG

siNA-

GmCmAmGmAmAmUmGmAmAmU

mCmAmCfAmAmGfAmGmUfAmGps

222

mUpsmU

ds-
4827
mApsmGpsmAmCfAmAmGmGfAfAf
4829
vmUpsfUpsmUmGmUmAmAmUmCm

siNA-

CmUmGfAmUmUmAmCfApsmApsm

AmGmUmUfCmCmUmUmGmUmCm

223

A

UpsmUpsmU

ds-
4828
fCpsmUpsfAmCfUmCfUmUfGmUfGm
4830
vmApsfUpsmUfCmAfUmUfCmUfGmC

siNA-

CfAmGfAmAfUmGfApsmApsfU

fAmCfAmAfGmAfGmUfAmGpsmUps

224

mU

mX = 2′-O-methyl nucleotide;

fX = 2′-fluoro nucleotide;

ps = phosphorothioate linkage;

vX = 5′ vinyl phosphonate nucleotide;

vmX = 5′ vinyl phosphonate, 2′-O-methyl nucleotide

In some embodiments, a siNA of the present disclosure may comprise a sense strand selected from any one of SEQ ID NOs: 4383 to 4604, 4827, and 4828. In some embodiments, a siNA of the present disclosure may comprise an antisense strand selected from any one of SEQ ID NOs: 4605 to 4826, 4829, and 4830. In some embodiments, a siNA of the present disclosure may comprise a sense strand selected from any one of SEQ ID NOs: 4383 to 4604, 4827, and 4828 and an antisense strand selected from any one of SEQ ID NOs: 4605 to 4826, 4829, and 4830. In some embodiments, a siNA of the present disclosure may comprise a sense strand and an antisense strand, respectively, selected from SEQ ID NOs:

4383 and 4605;

4384 and 4606;

4385 and 4607;

4386 and 4608;

4387 and 4609;

4388 and 4610;

4389 and 4611;

4390 and 4612;

4391 and 4613;

4392 and 4614;

4393 and 4615;

4394 and 4616;

4395 and 4617;

4396 and 4618;

4397 and 4619;

4398 and 4620;

4399 and 4621;

4400 and 4622;

4401 and 4623;

4402 and 4624;

4403 and 4625;

4404 and 4626;

4405 and 4627;

4406 and 4628;

4407 and 4629;

4408 and 4630;

4409 and 4631;

4410 and 4632;

4411 and 4633;

4412 and 4634;

4413 and 4635;

4414 and 4636;

4415 and 4637;

4416 and 4638;

4417 and 4639;

4418 and 4640;

4419 and 4641;

4420 and 4642;

4421 and 4643;

4422 and 4644;

4423 and 4645;

4424 and 4646;

4425 and 4647;

4426 and 4648;

4427 and 4649;

4428 and 4650;

4429 and 4651;

4430 and 4652;

4431 and 4653;

4432 and 4654;

4433 and 4655;

4434 and 4656;

4435 and 4657;

4436 and 4658;

4437 and 4659;

4438 and 4660;

4439 and 4661;

4440 and 4662;

4441 and 4663;

4442 and 4664;

4443 and 4665;

4444 and 4666;

4445 and 4667;

4446 and 4668;

4447 and 4669;

4448 and 4670;

4449 and 4671;

4450 and 4672;

4451 and 4673;

4452 and 4674;

4453 and 4675;

4454 and 4676;

4455 and 4677;

4456 and 4678;

4457 and 4679;

4458 and 4680;

4459 and 4681;

4460 and 4682;

4461 and 4683;

4462 and 4684;

4463 and 4685;

4464 and 4686;

4465 and 4687;

4466 and 4688;

4467 and 4689;

4468 and 4690;

4469 and 4691;

4470 and 4692;

4471 and 4693;

4472 and 4694;

4473 and 4695;

4474 and 4696;

4475 and 4697;

4476 and 4698;

4477 and 4699;

4478 and 4700;

4479 and 4701;

4480 and 4702;

4481 and 4703;

4482 and 4704;

4483 and 4705;

4484 and 4706;

4485 and 4707;

4486 and 4708;

4487 and 4709;

4488 and 4710;

4489 and 4711;

4490 and 4712;

4491 and 4713;

4492 and 4714;

4493 and 4715;

4494 and 4716;

4495 and 4717;

4496 and 4718;

4497 and 4719;

4498 and 4720;

4499 and 4721;

4500 and 4722;

4501 and 4723;

4502 and 4724;

4503 and 4725;

4504 and 4726;

4505 and 4727;

4506 and 4728;

4507 and 4729;

4508 and 4730;

4509 and 4731;

4510 and 4732;

4511 and 4733;

4512 and 4734;

4513 and 4735;

4514 and 4736;

4515 and 4737;

4516 and 4738;

4517 and 4739;

4518 and 4740;

4519 and 4741;

4520 and 4742;

4521 and 4743;

4522 and 4744;

4523 and 4745;

4524 and 4746;

4525 and 4747;

4526 and 4748;

4527 and 4749;

4528 and 4750;

4529 and 4751;

4530 and 4752;

4531 and 4753;

4532 and 4754;

4533 and 4755;

4534 and 4756;

4535 and 4757;

4536 and 4758;

4537 and 4759;

4538 and 4760;

4539 and 4761;

4540 and 4762;

4541 and 4763;

4542 and 4764;

4543 and 4765;

4544 and 4766;

4545 and 4767;

4546 and 4768;

4547 and 4769;

4548 and 4770;

4549 and 4771;

4550 and 4772;

4551 and 4773;

4552 and 4774;

4553 and 4775;

4554 and 4776;

4555 and 4777;

4556 and 4778;

4557 and 4779;

4558 and 4780;

4559 and 4781;

4560 and 4782;

4561 and 4783;

4562 and 4784;

4563 and 4785;

4564 and 4786;

4565 and 4787;

4566 and 4788;

4567 and 4789;

4568 and 4790;

4569 and 4791;

4570 and 4792;

4571 and 4793;

4572 and 4794;

4573 and 4795;

4574 and 4796;

4575 and 4797;

4576 and 4798;

4577 and 4799;

4578 and 4800;

4579 and 4801;

4580 and 4802;

4581 and 4803;

4582 and 4804;

4583 and 4805;

4584 and 4806;

4585 and 4807;

4586 and 4808;

4587 and 4809;

4588 and 4810;

4589 and 4811;

4590 and 4812;

4591 and 4813;

4592 and 4814;

4593 and 4815;

4594 and 4816;

4595 and 4817;

4596 and 4818;

4597 and 4819;

4598 and 4820;

4599 and 4821;

4600 and 4822;

4601 and 4823;

4602 and 4824;

4603 and 4825;

4604 and 4826;

4827 and 4829; &

4828 and 4830.

In some embodiments, the siNA can be selected from ds-siNA-196 (sense and antisense respectively comprising SEQ ID NOs: 4578 and 4800), ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs: 4579 and 4801), ds-siNA-198 (sense and antisense respectively comprising SEQ ID NOs: 4580 and 4802), ds-siNA-199 (sense and antisense respectively comprising SEQ ID NOs: 4581 and 4803), ds-siNA-217 (sense and antisense respectively comprising SEQ ID NOs: 4599 and 4821), ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisense respectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisense respectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs: 4603 and 4825), and ds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs: 4604 and 4826).

In some embodiments, the siNA can be selected from ds-siNA-196 (sense and antisense respectively comprising SEQ ID NOs: 4578 and 4800), ds-siNA-197 (sense and antisense respectively comprising SEQ ID NOs: 4579 and 4801), ds-siNA-198 (sense and antisense respectively comprising SEQ ID NOs: 4580 and 4802), and ds-siNA-199 (sense and antisense respectively comprising SEQ ID NOs: 4581 and 4803). These siNA comprise a 5′-vinyl phosphonate and are derived from siRNAs that showed high potency in the live virus assay prior to the incorporation of the 5′-vinyl phosphonate. It was determined that the 5′-VP further improved potency for all constructs (see Examples). The most potent siNA were ds-siNA-196 and ds-siNA-199, which were selected for further modification.

In some embodiments, the siNA can be selected from, ds-siNA-217 (sense and antisense respectively comprising SEQ ID NOs: 4599 and 4821), ds-siNA-218 (sense and antisense respectively comprising SEQ ID NOs: 4600 and 4822), ds-siNA-219 (sense and antisense respectively comprising SEQ ID NOs: 4601 and 4823), ds-siNA-220 (sense and antisense respectively comprising SEQ ID NOs: 4602 and 4824), ds-siNA-221 (sense and antisense respectively comprising SEQ ID NOs: 4603 and 4825), and ds-siNA-222 (sense and antisense respectively comprising SEQ ID NOs: 4604 and 4826). These siNA are further modified forms of ds-siNA-196 and ds-siNA-199, which have different 2′-fluoro contents (three variants for each one of the parent siRNAs). All of these siNA also showed high potency across screening assays (see Examples).

Additionally, analogs of the specific embodiments (ds-siNA-001 to ds-siNA-224) can be prepared by altering or adjusting the modified nucleotides, phosphorylation blockers, 5′-stabilized end caps, and/or linkers as disclosed herein. For example, ds-siNA-223 is an analog of ds-siNA-196 in which an additional ps and mUmU overhang have been incorporated in place of dTdT. Similarly, ds-siNA-224 is an analog of ds-siNA-199 in which an additional ps and mUmU overhang have been incorporated in place of dTdT. Those skilled in the art will understand that other analogs can be similarly constructed.

Any of the foregoing specific embodiments can be incorporated into a pharmaceutical compositions, either alone or in combination with 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more additional siNA disclosed herein. Any of the foregoing specific embodiments can be used to treat or prevent viral infections, such as coronavirus infections (e.g., COVID-19) pursuant to the methods and uses disclosed herein.

Pharmaceutical Compositions

The present disclosure also encompasses pharmaceutical compositions comprising siNAs of the present disclosure. One embodiment is a pharmaceutical composition comprising one or more siNA of the present disclosure, and a pharmaceutically acceptable diluent or carrier.

In some embodiments, the pharmaceutical compositions comprising any of the siNA molecules, sense strands, antisense strands, first nucleotide sequences, or second nucleotide sequences described herein. The compositions may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more siNA molecules described herein. The compositions may comprise a first nucleotide sequence (i.e., a sense strand) comprising a nucleotide sequence of any one SEQ ID NOs: 1-1203, 2411-3392, 4383-4604, 4827, and 4828. In some embodiments, the composition comprises a second nucleotide sequence (i.e., antisense strand) comprising a nucleotide sequence of any one of SEQ ID NOs: 1204-2406, 3393-4374, 4605-4826, 4829, and 4830. In some embodiments, the composition comprises a sense strand comprising a nucleotide sequence of any one of SEQ ID NOs: 1-1203, 2411-3392, 4383-4604, 4827, and 4828. In some embodiments, the composition comprises an antisense strand comprising a nucleotide sequence of any one of SEQ ID NOs: 1204-2406, 3393-4374, 4605-4826, 4829, and 4830.

Alternatively or additionally, the pharmaceutical compositions may comprise (a) a phosphorylation blocker; and (b) a siNA. In some embodiments, the phosphorylation blocker is any of the phosphorylation blockers disclosed herein. In some embodiments, the siNA is any of the siNAs disclosed herein. In some embodiments, the siNA comprises any of the sense strands, antisense strands, first nucleotide sequences, or second nucleotide sequences described herein.

In some embodiments, the siNA comprises any of the sense strands, antisense strands, first nucleotide sequences, or second nucleotide sequences described herein. In some embodiments, the siNA comprises one or more modified nucleotides. In some embodiments, the one or more modified nucleotides are independently selected from a 2′-fluoro nucleotide and a 2′-O-methyl nucleotide. In some embodiments, the 2′-fluoro nucleotide or the 2′-O-methyl nucleotide is independently selected from any of the 2′-fluoro or 2′-O-methyl nucleotide mimics disclosed herein. In some embodiments, the siNA comprises a nucleotide sequence comprising any of the modification patterns disclosed herein. In some embodiments, the composition comprises (a) a conjugated moiety; and (b) a short interfering nucleic acid (siNA). In some embodiments, the siNA is any of the siNAs disclosed herein. In some embodiments, the siNA comprises any of the sense strands, antisense strands, first nucleotide sequences, or second nucleotide sequences described herein.

In some embodiments, the pharmaceutical composition comprises (a) a 5′-stabilized end cap; and (b) a siNA. In some embodiments, the 5′-stabilized end cap is any of the 5-stabilized end caps disclosed herein. In some embodiments, the siNA is any of the siNAs disclosed herein. In some embodiments, the siNA comprises any of the sense strands, antisense strands, first nucleotide sequences, or second nucleotide sequences described herein. In some embodiments, the siNA comprises one or more modified nucleotides. In some embodiments, the one or more modified nucleotides are independently selected from a 2′-fluoro nucleotide and a 2′-O-methyl nucleotide. In some embodiments, the 2′-fluoro nucleotide or the 2′-O-methyl nucleotide is independently selected from any of the 2′-fluoro or 2′-O-methyl nucleotide mimics disclosed herein. In some embodiments, the siNA comprises a nucleotide sequence comprising any of the modification patterns disclosed herein.

In some embodiments, the pharmaceutical composition comprises (a) at least one phosphorylation blocker, conjugated moiety, or 5′-stabilized end cap; and (b) a short interfering nucleic acid (siNA). In some embodiments, the phosphorylation blocker is any of the phosphorylation blockers disclosed herein. In some embodiments, the 5′-stabilized end cap is any of the 5-stabilized end caps disclosed herein. In some embodiments, the siNA is any of the siNAs disclosed herein. In some embodiments, the siNA comprises any of the sense strands, antisense strands, first nucleotide sequences, or second nucleotide sequences described herein. In some embodiments, the siNA comprises one or more modified nucleotides. In some embodiments, the one or more modified nucleotides are independently selected from a 2′-fluoro nucleotide and a 2′-O-methyl nucleotide. In some embodiments, the 2′-fluoro nucleotide or the 2′-O-methyl nucleotide is independently selected from any of the 2′-fluoro or 2′-O-methyl nucleotide mimics disclosed herein. In some embodiments, the siNA comprises a nucleotide sequence comprising any of the modification patterns disclosed herein.

In some embodiments, the pharmaceutical composition containing the siNA of the present disclosure is formulated for systemic administration via parenteral delivery. Parenteral administration includes intravenous, intra-arterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; also subdermal administration, e.g., via an implanted device. In a preferred embodiment, the pharmaceutical composition containing the siNA of the present disclosure is formulated for subcutaneous (SC) or intravenous (IV) delivery. Formulations for parenteral administration may include sterile aqueous solutions, which may also contain buffers, diluents and other pharmaceutically acceptable additives as understood by the skilled artisan. For intravenous use, the total concentration of solutes may be controlled to render the preparation isotonic.

The pharmaceutical compositions containing the siNA of the present disclosure are useful for treating a disease or disorder, e.g., associated with the expression or activity of a coronavirus gene, more specifically a non-structural protein, such as nsp8, nsp9, nsp10, nsp11, nsp12, nsp13, nsp14, or nsp15.

In some embodiments, the pharmaceutical composition comprises a siNA of the present disclosure that is complementary or hybridizes to a viral target RNA sequence (e.g., a non-structural protein of coronavirus), and a pharmaceutically acceptable diluent or carrier. When the pharmaceutical composition comprises two or more siNAs, the siNAs may be present in varying amounts. For example, in some embodiments, the weight ratio of first siNA to second siNA is 1:4 to 4:1, e.g., 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, or 4:1. In some embodiments, the molar ratio of first siNA to second siNA is 1:4 to 4:1, e.g., 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, or 4:1.

In some embodiments, the pharmaceutical composition comprises an amount of one or more of the siNA molecules described herein formulated with one or more pharmaceutically acceptable carriers (additives) and/or diluents. The pharmaceutical compositions may be specially formulated for administration in solid or liquid form, including those adapted for the following: (1) parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustained-release formulation; (2) topical application, for example, as a cream, ointment, or a controlled-release patch or spray applied to the skin; (3) intravaginally or intrarectally, for example, as a pessary, cream or foam; (4) sublingually; (5) ocularly; (6) transdermally; or (7) nasally.

Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions.

Examples of pharmaceutically-acceptable antioxidants include: (1) water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol, and the like; and (3) metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like.

Formulations of the present disclosure include those suitable for nasal, topical (including buccal and sublingual), rectal, vaginal and/or parenteral administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will vary depending upon the host being treated, the particular mode of administration. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound (e.g., siNA molecule) which produces a therapeutic effect. Generally, out of one hundred percent, this amount will range from about 0.1 percent to about ninety-nine percent of active ingredient, preferably from about 5 percent to about 70 percent, most preferably from about 10 percent to about 30 percent.

In some embodiments, a formulation of the present disclosure comprises an excipient selected from the group consisting of cyclodextrins, celluloses, liposomes, micelle forming agents, e.g., bile acids, and polymeric carriers, e.g., polyesters and polyanhydrides; and a compound (e.g., siNA molecule) of the present disclosure.

Methods of preparing these formulations or compositions include the step of bringing into association a compound (e.g., siNA molecule) of the present disclosure with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound (e.g., siNA molecule) of the present disclosure with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product.

Formulations of the disclosure suitable for a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, each containing a predetermined amount of a compound (e.g., siNA molecule) of the present disclosure as an active ingredient. A compound (e.g., siNA molecule) of the present disclosure may also be administered as a bolus, electuary, or paste.

In dosage forms of the disclosure, the active ingredient may be mixed with one or more pharmaceutically-acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds and surfactants, such as poloxamer and sodium lauryl sulfate; (7) wetting agents, such as, for example, cetyl alcohol, glycerol monostearate, and non-ionic surfactants; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, zinc stearate, sodium stearate, stearic acid, and mixtures thereof; (10) coloring agents; and (11) controlled release agents such as crospovidone or ethyl cellulose.

The disclosed dosage forms may be sterilized by, for example, filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient(s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients.

Liquid dosage forms of the compounds (e.g., siNA molecules) of the disclosure include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (I particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.

Besides inert diluents, the compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents.

Suspensions, in addition to the active compounds (e.g., siNA molecules), may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

Formulations of the pharmaceutical compositions of the disclosure for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing one or more compounds (e.g., siNA molecules) of the disclosure with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active compound (e.g., siNA molecule).

Formulations of the present disclosure which are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate.

Dosage forms for the topical or transdermal administration of a compound (e.g., siNA molecule) of this disclosure include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound (e.g., siNA molecule) may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants which may be required.

The ointments, pastes, creams and gels may contain, in addition to an active compound (e.g., siNA molecule) of this disclosure, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

Powders and sprays can contain, in addition to a compound (e.g., siNA molecule) of this disclosure, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.

Transdermal patches have the added advantage of providing controlled delivery of a compound (e.g., siNA molecule) of the present disclosure to the body. Such dosage forms can be made by dissolving or dispersing the compound (e.g., siNA molecule) in the proper medium. Absorption enhancers can also be used to increase the flux of the compound (e.g., siNA molecule) across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the compound (e.g., siNA molecule) in a polymer matrix or gel.

Ophthalmic formulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of this invention.

Pharmaceutical compositions of this disclosure suitable for parenteral administration comprise one or more compounds (e.g., siNA molecules) of the disclosure in combination with one or more pharmaceutically-acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain sugars, alcohols, antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents.

Examples of suitable aqueous and nonaqueous carriers which may be employed in the pharmaceutical compositions of the disclosure include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants.

These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms upon the subject compounds may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption such as aluminum monostearate and gelatin.

In some cases, in order to prolong the effect of a drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material having poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally-administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.

Injectable depot forms are made by forming microencapsule matrices of the subject compounds (e.g., siNA molecules) in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissue.

When the compounds (e.g., siNA molecules) of the present disclosure are administered as pharmaceuticals, to humans and animals, they can be given per se or as a pharmaceutical composition containing, for example, 0.1 to 99% (more preferably, 10 to 30%) of active ingredient in combination with a pharmaceutically acceptable carrier.

Methods of Treatment and Administration

The siNA molecules of the present disclosure may be used to treat or prevent a disease in a subject in need thereof. In some embodiments, a method of treating or preventing a disease in a subject in need thereof comprises administering to the subject any of the siNA molecules disclosed herein. In some embodiments, a method of treating or preventing a disease in a subject in need thereof comprises administering to the subject any of the compositions disclosed herein.

In some embodiments of the disclosed methods and uses, the disease is a respiratory disease. In some embodiments, the respiratory disease is a viral infection. In some embodiments, the respiratory disease is viral pneumonia. In some embodiments, the respiratory disease is an acute respiratory infection. In some embodiments, the respiratory disease is a cold. In some embodiments, the respiratory disease is severe acute respiratory syndrome (SARS). In some embodiments, the respiratory disease is Middle East respiratory syndrome (MERS). In some embodiments, the disease is coronavirus disease 2019 (e.g., COVID-19). In some embodiments, the respiratory disease can include one or more symptoms selected from coughing, sore throat, runny nose, sneezing, headache, fever, shortness of breath, myalgia, abdominal pain, fatigue, difficulty breathing, persistent chest pain or pressure, difficulty waking, loss of smell and taste, muscle or joint pain, chills, nausea or vomiting, nasal congestion, diarrhea, haemoptysis, conjunctival congestion, sputum production, chest tightness, and palpitations. In some embodiments, the respiratory disease can include complications selected from sinusitis, otitis media, pneumonia, acute respiratory distress syndrome, disseminated intravascular coagulation, pericarditis, and kidney failure. In some embodiments, the respiratory disease is idiopathic.

In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human primate. In some embodiments, the subject is a cat. In some embodiments, the subject is a camel. In preferred embodiments in which the subject is a human, the subject may be at least 40 years old, at least 45 years old, at least 50 years old, at least 55 years old, at least 60 years old, at least 65 years old, at least 70 years old, at least 75 years old, or at least 80 years old or older. In some embodiments, the subject is a pediatric subject (i.e., less than 18 years old).

The preparations (e.g., siNA molecules or pharmaceutical compositions thereof) of the present disclosure may be given parenterally, topically, or rectally or administered in the form of an inhalant. They are, of course, given in forms suitable for each administration route. For example, they are administered in tablets or capsule form, administration by injection, infusion, or inhalation; topical by lotion or ointment; rectal by suppositories. Injection, infusion, or inhalation are preferred.

These compounds may be administered to humans and other animals for therapy or as a prophylactic by any suitable route of administration, including nasally (as by, for example, a spray), rectally, intravaginally, parenterally, intracisternally and topically, as by powders, ointments or drops, including buccally and sublingually. In some embodiments, the compounds or compositions are inhaled, as by, for example, an inhaler, a nebulizer, or in an aerosolized form.

Regardless of the route of administration selected, the compounds (e.g., siNA molecules) of the present disclosure, which may be used in a suitable hydrated form, and/or the pharmaceutical compositions of the present disclosure, are formulated into pharmaceutically-acceptable dosage forms by conventional methods known to those of skill in the art.

In some embodiments, the present disclosure provides methods of treating or preventing a coronavirus infection, comprising administering to a subject in need thereof a therapeutically effective amount of one or more of the siNAs or a pharmaceutical composition as disclosed herein. In some embodiments, the coronavirus infection is selected from the group consisting of Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and COVID-19. In some embodiments, the subject has been treated with one or more additional coronavirus treatment agents. In some embodiments, the subject is concurrently treated with one or more additional coronavirus treatment agents.

Actual dosage levels of the active ingredients (e.g., siNA molecules) in the pharmaceutical compositions of this disclosure may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.

The selected dosage level will depend upon a variety of factors including the activity of the particular compound (e.g., siNA molecule) of the present disclosure employed, or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion or metabolism of the particular compound being employed, the rate and extent of absorption, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts.

A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the compounds (e.g., siNA molecules) of the disclosure employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.

In general, a suitable daily dose of a compound (e.g., siNA molecule) of the disclosure is the amount of the compound that is the lowest dose effective to produce a therapeutic effect. Such an effective dose generally depends upon the factors described above. Preferably, the compounds are administered at about 0.01 mg/kg to about 200 mg/kg, more preferably at about 0.1 mg/kg to about 100 mg/kg, even more preferably at about 0.5 mg/kg to about 50 mg/kg. In some embodiments, the compound is administered at a dose equal to or greater than 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.30, 0.35, 0.40, 0.45, 0.50, 0.55, 0.60, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, or 1 mg/kg. In some embodiments, the compound is administered at a dose equal to or less than 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, or 15 mg/kg. In some embodiments, the total daily dose of the compound is equal to or greater than 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 100 mg.

If desired, the effective daily dose of the active compound (e.g., siNA) may be administered as two, three, four, five, six, seven, eight, nine, ten or more doses or sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms. In some embodiments, the compound is administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 times. Preferred dosing is one administration per day. In some embodiments, the compound is administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 times a week. In some embodiments, the compound is administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 times a month. In some embodiments, the compound is administered once every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 days. In some embodiments, the compound is administered every 3 days. In some embodiments, the compound is administered once every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks. In some embodiments, the compound is administered every month. In some embodiments, the compound is administered once every 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 months. In some embodiments, the compound is administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53 times over a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 days. In some embodiments, the compound is administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53 times over a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53 weeks. In some embodiments, the compound is administered at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53 times over a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, or 53 months. In some embodiments, the compound is administered at least once a week for a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 weeks. In some embodiments, the compound is administered at least once a week for a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 months. In some embodiments, the compound is administered at least twice a week fora period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 weeks. In some embodiments, the compound is administered at least twice a week for a period of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 months. In some embodiments, the compound is administered at least once every two weeks for a period of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 weeks. In some embodiments, the compound is administered at least once every two weeks for a period of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 months. In some embodiments, the compound is administered at least once every four weeks fora period of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 weeks. In some embodiments, the compound is administered at least once every four weeks for a period of at least 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, or 70 months.

In some embodiments, any one of the siNAs or compositions disclosed herein is administered in a particle or viral vector. In some embodiments, the viral vector is a vector of adenovirus, adeno-associated virus (AAV), alphavirus, flavivirus, herpes simplex virus, lentivirus, measles virus, picornavirus, poxvirus, retrovirus, or rhabdovirus. In some embodiments, the viral vector is a recombinant viral vector. In some embodiments, the viral vector is selected from AAVrh.74, AAVrh.10, AAVrh.20, AAV-1, AAV-2, AAV-3, AAV-4, AAV-5, AAV-6, AAV-7, AAV-8, AAV-9, AAV-10, AAV-11, AAV-12 and AAV-13.

The subject of the described methods may be a mammal, and it includes humans and non-human mammals. In some embodiments, the subject is a human, such as an adult human.

The disclosed siNA can be administered alone or in combination with one or more additional coronavirus treatment agents and/or antiviral agents. The additional coronavirus treatment agent and/or antiviral may be a small molecule (e.g., a nucleoside analog or a protease inhibitor) or a biologic (e.g., an antibody or peptide). Examples of suitable coronavirus treatment agents include, but are not limited to, remdesivir, favipiravir, molnupiravir, dexamethasone, bamlanivimab, casirivimab, imdevimab, convalescent plasma, and interferons. Examples of suitable antiviral agents include, but are not limited to, baloxavir marboxil, oseltamivir, anamivir, vidarabine, acyclovir, ganciclovir, zidovudine, didanosine, zalcitabine, lamivudine, saquinavir, ritonavir, indinavir, nelfinavir, ribavirin, amantadine, rimantadine, remdesivir, favipiravir, and molnupiravir.

When the compounds (e.g., siNA molecules) described herein are co-administered with another, the effective amount may be less than when the compound is used alone.

Examples
Example 1: siNA Synthesis

This example describes an exemplary method for synthesizing ds-siNAs, such as the siNAs disclosed in Table 6 (as identified by the ds-siNA ID).

The 2′-OMe phosphoramidite 5′-O-DMT-deoxy Adenosine (NH-Bz), 3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite, 5′-O-DMT-deoxy Guanosine (NH-ibu), 3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite, 5′-O-DMT-deoxy Cytosine (NH-Bz), 3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite, 5′-O-DMT-Uridine 3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite and solid supports were purchased from Chemgenes Corp. MA.

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The 2′-F-5′-O-DMT-(NH-Bz) Adenosine-3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite, 2′-F-5′-O-DMT-(NH-ibu)-Guanosine, 3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite, 5′-O-DMT-(NH-Bz)-Cytosine, 2′-F-3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite, 5′-O-DMT-Uridine, 2′-F-3′-O-(2-cyanoethyl-N,N-diisopropyl phosphoramidite and solid supports were purchased from Thermo Fischer Milwaukee Wis., USA.

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All the monomers were dried in vacuum desiccator with desiccants (P₂O₅, RT 24 h). The solid supports (CPG) attached to the nucleosides and universal supports was obtained from LGC and Chemgenes. The chemicals and solvents for post synthesis workflow were purchased from commercially available sources like VWR/Sigma and used without any purification or treatment. Solvent (Acetonitrile) and solutions (amidite and activator) were stored over molecular sieves during synthesis.

The oligonucleotides were synthesized on a DNA/RNA Synthesizers (Expedite 8909 or ABI-394) using standard oligonucleotide phosphoramidite chemistry starting from the 3′ residue of the oligonucleotide preloaded on CPG support. An extended coupling of 0.1M solution of phosphoramidite in CH₃CN in the presence of 5-(ethylthio)-1H-tetrazole activator to a solid bound oligonucleotide followed by standard capping, oxidation and deprotection afforded modified oligonucleotides. The 0.1M 12, THF:Pyridine; Water-7:2:1 was used as oxidizing agent while DDTT ((dimethylamino-methylidene) amino)-3H-1,2,4-dithiazaoline-3-thione was used as the sulfur-transfer agent for the synthesis of oligoribonucleotide phosphorothioates. The stepwise coupling efficiency of all modified phosphoramidites was more than 98%.

Reagents
Detailed Description

Deblock Solution
3% Dichloroacetic acid (DCA) in

Dichloromethane (DCM)

Amidite Concentration
0.1M in Anhydrous Acetonitrile

Activator
0.25M Ethyl-thio-Tetrazole (ETT)

Cap-A solution
Acetic anhydride in Pyridine/THF

Cap-B Solution
16% 1-Methylimidazole in THF

Oxidizing Solution
0.02M I₂, THF:Pyridine; Water-7:2:1

Sulfurizing Solution
0.2M DDTT in Pyridine/Acetonitrile 1:1

Cleavage and Deprotection

Deprotection and cleavage from the solid support was achieved with mixture of ammonia methylamine (1:1, AMA) for 15 min at 65° C., when the universal linker was used, the deprotection was left for 90 min at 65° C. or solid supports were heated with aqueous ammonia (28%) solution at 55° C. for 16 h to deprotect the base labile protecting groups.

Quantitation of Crude SiNA or Raw Analysis

Samples were dissolved in deionized water (1.0 mL) and quantitated as follows: Blanking was first performed with water alone (2 ul) on Nanodrop then Oligo sample reading obtained at 260 nm. The crude material is dried down and stored at −20° C.

Crude HPLC/LC-MS analysis

The 0.1 OD of the crude samples were analyzed for crude HPLC and LC-MS analysis. After Confirming the crude LC-MS data then purification step was performed.

HPLC Purification

The unconjugated oligonucleotides were purified by anion-exchange HPLC. The buffers were 20 mM sodium phosphate in 10% CH₃CN, pH 8.5 (buffer A) and 20 mM sodium phosphate in 10% CH₃CN, 1.0 M NaBr, pH 8.5 (buffer B). Fractions containing full-length oligonucleotides were pooled.

Desalting of Purified SiNA

The purified dry siNA was then desalted using Sephadex G-25 M (Amersham Biosciences). The cartridge was conditioned with 10 mL of deionized water thrice. Finally, the purified siNA dissolved thoroughly in 2.5 mL RNAse free water was applied to the cartridge with very slow drop wise elution. The salt free siNA was eluted with 3.5 ml deionized water directly into a screw cap vial.

IEX HPLC and Electrospray LC/MS Analysis

Approximately 0.10 OD of siNA is dissolved in water and then pipetted in special vials for IEX-HPLC and LC/MS analysis. Analytical HPLC and ES LC-MS established the integrity of the compounds.

Duplex Preparation

Single strand oligonucleotides (Sense and Antisense strands) were annealed (1:1 by molar equivalents, heat 90° C. for 3 min followed by room temperature, 20 min) to give the duplex ds-siNA. The final compounds were analyzed on size exclusion chromatography (SEC).

Example 2: Synthesis of 5′ End Cap Monomer

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Example 2 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (15 g, 57.90 mmol) in DMF (150 mL) were added AcSK (11.24 g, 98.43 mmol) and TBAI (1.07 g, 2.89 mmol), and the mixture was stirred at 25° C. for 12 h. Upon completion as monitored by LCMS, the mixture was diluted with H₂O (10 mL) and extracted with EA (200 mL*3). The combined organic layers were washed with brine (200 mL*3), dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure to give 2 (14.5 g, 96.52% yield, 98% purity) as a colorless oil. ESI-LCMS: 254.28 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=4.78-4.65 (m, 2H), 3.19 (d, J=14.1 Hz, 2H), 2.38 (s, 3H), 1.32 (t, J=6.7 Hz, 12H); ³¹P NMR (162 MHz, CDCl₃) δ=20.59.

Preparation of (3): To a solution of 2 (14.5 g, 57.02 mmol) in CH₃CN (50 mL) and MeOH (25 mL) was added NaOH (3 M, 28.51 mL), and the mixture was stirred at 25° C. for 12 h under Ar. Upon completion as monitored by TLC, the reaction mixture was concentrated under reduced pressure to remove CH₃CN and CH₃OH. The residue was diluted with water (50 mL) and adjust pH=7 by 6M HCl, and the mixture was extracted with EA (50 mL*3). The combined organic layers were washed with brine (50 mL*3), dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure to give 3 (12.1 g, crude) as a colorless oil.

Preparation of (4): To a solution of 3 (12.1 g, 57.01 mmol) in CH₃CN (25 mL) and MeOH (25 mL) was added A (14.77 g, 57.01 mmol) dropwise at 25° C., and the mixture was stirred at 25° C. under Ar for 12 h. Upon completion as monitored by LCMS, the reaction mixture was concentrated under reduced pressure to give 4 (19.5 g, 78.85% yield) as a colorless oil. ¹H NMR (400 MHz, CDCl₃) δ=4.80-4.66 (m, 4H), 2.93 (d, J=11.3 Hz, 4H), 1.31 (dd, J=3.9, 6.1 Hz, 24H); ³¹P NMR (162 MHz, CDCl₃) δ=22.18.

Preparation of (5): To a solution of 4 (19.5 g, 49.95 mmol) in MeOH (100 mL) and H₂O (100 mL) was added Oxone (61.41 g, 99.89 mmol) at 25° C. in portions, and the mixture was stirred at 25° C. for 12 h under Ar. Upon completion as monitored by LCMS, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to remove MeOH. The residue was extracted with EA (50 mL*3). The combined organic layers were washed with brine (50 mL*3), dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The crude product was triturated with i-Pr₂O and n-Hexane (1:2, 100 mL) at 25° C. for 30 min to give 5 (15.6 g, 73.94% yield,) as a white solid. ¹H NMR (400 MHz, CDCl₃) δ=4.92-4.76 (m, 4H), 4.09 (d, J=16.1 Hz, 4H), 1.37 (dd, J=3.5, 6.3 Hz, 24H); ³¹P NMR (162 MHz, CDCl₃) δ=10.17.

Preparation of (7): To a mixture of 5 (6.84 g, 16.20 mmol) in THF (20 mL) was added LiBr (937.67 mg, 10.80 mmol) until dissolved, followed by DIEA (1.40 g, 10.80 mmol, 1.88 mL) under argon at 15° C. The mixture was stirred at 15° C. for 15 min. 6 (4 g, 10.80 mmol) were added. The mixture was stirred at 15° C. for 3 h. Upon completion as monitored by LCMS, the reaction mixture was quenched by addition of H₂O (40 mL) and extracted with EA (40 mL*3). The combined organic layers were washed with brine (100 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash reverse-phase chromatography (120 g C-18 Column, Eluent of 0˜60% ACN/H₂O gradient @ 80 mL/min) to give 7 (5.7 g, 61.95% yield) as a colorless oil. ESI-LCMS: 611.2 [M+H]⁺, ¹H NMR (400 MHz, CDCl₃); δ=9.26 (s, 1H), 7.50 (d, J=8.1 Hz, 1H), 7.01 (s, 2H), 5.95 (d, J=2.7 Hz, 1H), 5.80 (dd, J=2.1, 8.2 Hz, 1H), 4.89-4.72 (m, 2H), 4.66 (d, J=7.2 Hz, 1H), 4.09-4.04 (m, 1H), 3.77 (dd, J=2.7, 4.9 Hz, 1H), 3.62 (d, J=3.1 Hz, 1H), 3.58 (d, J=3.1 Hz, 1H), 3.52 (s, 3H), 1.36 (td, J=1.7, 6.1 Hz, 12H), 0.92 (s, 9H), 0.12 (s, 6H); ³¹P NMR (162 MHz, CDCl₃) δ=9.02

Preparation of (8): To a mixture of 7 (5.4 g, 8.84 mmol) in THF (80 mL) was added Pd/C (5.4 g, 10% purity) under N₂. The suspension was degassed under vacuum and purged with H₂several times. The mixture was stirred under H₂(15 psi) at 20° C. for 1 hr. Upon completion as monitored by LCMS, the reaction mixture was filtered, and the filtrate was concentrated to give 8 (5.12 g, 94.5% yield) as a white solid. ESI-LCMS: 613.3 [M+H]⁺; H NMR (400 MHz, CD₃CN) δ=9.31 (s, 1H), 7.37 (d, J=8.0 Hz, 1H), 5.80-5.69 (m, 2H), 4.87-4.75 (m, 2H), 4.11-4.00 (m, 1H), 3.93-3.85 (m, 1H), 3.80-3.74 (m, 1H), 3.66-3.60 (m, 1H), 3.57-3.52 (m, 1H), 3.49 (s, 3H), 3.46-3.38 (m, 1H), 2.35-2.24 (m, 1H), 2.16-2.03 (m, 1H), 1.89-1.80 (m, 1H), 1.37-1.34 (m, 12H), 0.90 (s, 9H), 0.09 (s, 6H); ³¹P NMR (162 MHz, CD₃CN) δ=9.41.

Preparation of (9): To a solution of 8 (4.4 g, 7.18 mmol) in THF (7.2 mL) was added TBAF (1 M, 7.18 mL), and the mixture was stirred at 20° C. for 1 hr. Upon completion as monitored by LCMS, the reaction mixture was diluted with H₂O (50 mL) and extracted with EA (50 mL*4). The combined organic layers were washed with brine (50 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, Eluent of 0˜5%, MeOH/DCM gradient @ 40 mL/min) to give 9 (3.2 g, 88.50% yield) as a white solid. ESI-LCMS: 499.2 [M+H]⁺¹; ¹H NMR (400 MHz, CD₃CN) δ=9.21 (s, 1H), 7.36 (d, J=8.3 Hz, 1H), 5.81-5.72 (m, 2H), 4.88-4.74 (m, 2H), 3.99-3.87 (m, 2H), 3.84 (dd, 5.4 Hz, 1H), 3.66-3.47 (m, 7H), 2.98 (s, 1H), 2.44-2.15 (m, 2H), 1.36 (d, J=6.0 Hz, 12H); ³¹P NMR (162 MHz, CD₃CN) δ=9.48.

Preparation of (Example 2 monomer): To a mixture of 9 (3.4 g, 6.82 mmol, 1 eq) and 4 A MS (3.4 g) in MeCN (50 mL) was added P1 (2.67 g, 8.87 mmol, 2.82 mL, 1.3 eq) at 0° C., followed by addition of 1H-imidazole-4,5-dicarbonitrile (886.05 mg, 7.50 mmol) at 0° C. The mixture was stirred at 20° C. for 2 h. Upon completion as monitored by LCMS, the reaction mixture was quenched by addition of saturated aq. NaHCO₃(50 mL) and diluted with DCM (100 mL). The organic layer was washed with saturated aq. NaHCO₃(50 mL*2), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC: column: YMC-Triart Prep C18 250*50 mm*10 um; mobile phase: [water (10 mM NH₄HCO₃)-ACN]; B %: 15% to give a impure product. The impure product was further purified by a flash silica gel column (0% to 5% i-PrOH in DCM with 0.5% TEA) to give Example 2 monomer (2.1 g, 43.18% yield) as a white solid. ESI-LCMS: 721.2 [M+Na]⁺; H NMR (400 MHz, CD₃CN) δ=9.29 (s, 1H), 7.45 (d, J=8.1 Hz, 1H), 5.81 (d, J=4.2 Hz, 1H), 5.65 (d, J=8.1 Hz, 1H), 4.79-4.67 (m, 2H), 4.26-4.05 (m, 2H), 4.00-3.94 (m, 1H), 3.89-3.63 (m, 6H), 3.53-3.33 (m, 5H), 2.77-2.61 (m, 2H), 2.31-2.21 (m, 1H), 2.16-2.07 (m, 1H), 1.33-1.28 (m, 12H), 1.22-1.16 (m, 1H), 1.22-1.16 (m, 11H); ³¹P NMR (162 MHz, CD₃CN) δ=149.89, 149.78, 10.07, 10.02.

Example 3: Synthesis of 5′ End Cap Monomer

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Example 3 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (5 g, 13.42 mmol) in DMF (50 mL) were added PPh₃(4.58 g, 17.45 mmol) and 2-hydroxyisoindoline-1,3-dione (2.85 g, 17.45 mmol), followed by a solution of DIAD (4.07 g, 20.13 mmol, 3.91 mL) in DMF (10 mL) dropwise at 15° C. The resulting solution was stirred at 15° C. for 18 hr. The reaction mixture was then diluted with DCM (50 mL), washed with H₂O (60 mL*3) and brine (30 mL), dried over Na₂SO₄, filtered and evaporated to give a residue. The residue was then triturated with EtOH (55 mL) for 30 min, and the collected white powder was washed with EtOH (10 mL*2) and dried to give 2 (12.2 g, 85.16% yield) as a white powder (the reaction was set up in two batches and combined) ESI-LCMS: 518.1 [M+H]⁺.

Preparation of (3): 2 (6 g, 11.59 mmol) was suspended in MeOH (50 mL), and then NH₂NH₂.H₂O (3.48 g, 34.74 mmol, 3.38 mL, 50% purity) was added dropwise at 20° C. The reaction mixture was stirred at 20° C. for 4 hr. Upon completion, the reaction mixture was diluted with EA (20 mL) and washed with NaHCO₃(10 mL*2) and brine (10 mL). The combined organic layers were then dried over Na₂SO₄, filtered and evaporated to give 3 (8.3 g, 92.5% yield) as a white powder. (The reaction was set up in two batches and combined). ESI-LCMS: 388.0 [M+H]⁺, ¹H NMR (400 MHz, DMSO-d₆) δ=11.39 (br s, 1H), 7.72 (d, J=8.1 Hz, 1H), 6.24-6.09 (m, 2H), 5.80 (d, J=4.9 Hz, 1H), 5.67 (d, J=8.1 Hz, 1H), 4.26 (t, J=4.9 Hz, 1H), 4.03-3.89 (m, 1H), 3.87-3.66 (m, 3H), 3.33 (s, 3H), 0.88 (s, 9H), 0.09 (d, J=1.3 Hz, 6H)

Preparation of (4): To a solution of 3 (7 g, 18.06 mmol) and Py (1.43 g, 18.06 mmol, 1.46 mL) in DCM (130 mL) was added a solution of MSCl (2.48 g, 21.68 mmol, 1.68 mL) in DCM (50 mL) dropwise at −78° C. under N₂. The reaction mixture was allowed to warm to 15° C. in 30 min and stirred at 15° C. for 3 h. The reaction mixture was quenched by addition of ice-water (70 mL) at 0° C., and then extracted with DCM (50 mL*3). The combined organic layers were washed with saturated aq. NaHCO₃(50 mL) and brine (30 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 30 g SepaFlash® Silica Flash Column, Eluent of 0˜20% i-PrOH/DCM gradient @ 30 mL/min to give 4 (6.9 g, 77.94% yield) as a white solid. ESI-LCMS: 466.1 [M+H]⁺, ¹H NMR (400 MHz, DMSO-d₆) δ=11.41 (br s, 1H), 10.15 (s, 1H), 7.69 (d, J=8.1 Hz, 1H), 5.80 (d, J=4.4 Hz, 1H), 5.65 (d, J=8.1 Hz, 1H), 4.24 (t, J=5.2 Hz, 1H), 4.16-3.98 (m, 3H), 3.87 (t, J=4.8 Hz, 1H), 3.00 (s, 3H), 2.07 (s, 3H), 0.88 (s, 9H), 0.10 (d, J=1.5 Hz, 6H)

Preparation of (5): To a solution of 4 (6.9 g, 14.82 mmol) in THF (70 mL) was added TBAF (1 M, 16.30 mL) at 15° C. The reaction mixture was stirred at 15° C. for 18 hr, and then evaporated to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 24 g SepaFlash® Silica Flash Column, Eluent of 0˜9% MeOH/Ethyl acetate gradient @ 30 mL/min) to give 5 (1.8 g, 50.8% yield) as a white solid. ESI-LCMS: 352.0 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=11.40 (s, 1H), 10.13 (s, 1H), 7.66 (d, J=8.1 Hz, 1H), 5.83 (d, J=4.9 Hz, 1H), 5.65 (dd, J=1.8, 8.1 Hz, 1H), 5.36 (d, J=6.2 Hz, 1H), 4.13-4.00 (m, 4H), 3.82 (t, J=5.1 Hz, 1H), 3.36 (s, 3H), 3.00 (s, 3H)

Preparation of (Example 3 monomer): To a mixture of 5 (3 g, 8.54 mmol) and DIEA (2.21 g, 17.08 mmol, 2.97 mL) in ACN (90 mL) was added P2 (3.03 g, 12.81 mmol) dropwise at 15° C. The reaction mixture was stirred at 15° C. for 5 h. Upon completion, the reaction mixture was diluted with EA (40 mL) and quenched with 5% NaHCO₃(20 mL). The organic layer was washed with brine (30 mL), dried over Na₂SO₄, filtered and evaporated to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜15% i-PrOH/(DCM with 2% TEA) gradient @ 20 mL/min) to Example 3 monomer (2.1 g, 43.93% yield) as a white solid. ESI-LCMS: 552.3 [M+H]⁺; ¹H NMR (400 MHz, CD₃CN) δ=8.78 (br s, 1H), 7.57 (dd, J=4.6, 8.2 Hz, 1H), 5.97-5.80 (m, 1H), 5.67 (d, J=8.3 Hz, 1H), 4.46-4.11 (m, 4H), 3.95-3.58 (m, 5H), 3.44 (d, J=16.3 Hz, 3H), 3.02 (d, J=7.5 Hz, 3H), 2.73-2.59 (m, 2H), 1.23-1.15 (m, 12H); ³¹P NMR (162 MHz, CD₃CN) δ=150.30, 150.10

Example 4: Synthesis of 5′ End Cap Monomer

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Example 4 Monomer Synthesis Scheme

Preparation of (2): To the solution of 1 (5 g, 12.90 mmol) and TEA (1.57 g, 15.48 mmol, 2.16 mL) in DCM (50 mL) was added P-4 (2.24 g, 15.48 mmol, 1.67 mL) in DCM (10 mL) dropwise at 15° C. under N₂. The reaction mixture was stirred at 15° C. for 3 h. Upon completion as monitored by LCMS and TLC (PE:EtOAc=0:1), the reaction mixture was concentrated to dryness, diluted with H₂O (20 mL), and extracted with EA (50 mL*3). The combined organic layers were washed with brine (30 mL*3), dried over anhydrous Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, Eluent of 0˜95% Ethyl acetate/Petroleum ether gradient @ 60 mL/min) to give 2 (5.3 g, 71.3% yield) as a white solid. ESI-LCMS: 496.1 [M+H]⁺; H NMR (400 MHz, CDCl₃) δ=0.10 (d, J=4.02 Hz, 6H) 0.91 (s, 9H) 3.42-3.54 (m, 3H) 3.65-3.70 (m, 1H) 3.76-3.89 (m, 6H) 4.00 (dd, J=10.92, 2.89 Hz, 1H) 4.08-4.13 (m, 1H) 4.15-4.23 (m, 2H) 5.73 (dd, J=8.28, 2.01 Hz, 1H) 5.84 (d, J=2.76 Hz, 1H) 6.86 (d, J=15.81 Hz, 1H) 7.72 (d, J=8.03 Hz, 1H) 9.10 (s, 1H); ³¹P NMR (162 MHz, CD₃CN) δ=9.65

Preparation of (3): To a solution of 2 (8.3 g, 16.75 mmol) in THF (50 mL) were added TBAF (1 M, 16.75 mL) and CH₃COOH (1.01 g, 16.75 mmol, 957.95 uL). The mixture was stirred at 20° C. for 12 hr. Upon completion as monitored by LCMS, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography (SiO₂, PE: EA=0˜100%; MeOH/EA=0˜10%) to give 3 (5 g, 77.51% yield) as a white solid. ESI-LCMS: 382.1 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=3.35 (s, 3H) 3.65 (br d, J=2.76 Hz, 3H) 3.68 (d, J=2.76 Hz, 3H) 3.77 (t, J=5.08 Hz, 1H) 3.84-4.10 (m, 4H) 5.33 (br d, J=5.52 Hz, 1H) 5.62 (d, J=7.77 Hz, 1H) 5.83 (d, J=4.94 Hz, 1H) 7.69 (d, J=7.71 Hz, 1H) 9.08 (d, J=16.81 Hz, 1H) 11.39 (br s, 1H); ³¹P NMR (162 MHz, CD₃CN) δ=15.41

Preparation of (Example 4 monomer): To a solution of 3 (2 g, 5.25 mmol) and DIPEA (2.03 g, 15.74 mmol, 2.74 mL, 3 eq) in MeCN (21 mL) and pyridine (7 mL) was added P2 (1.86 g, 7.87 mmol) dropwise at 20° C., and the mixture was stirred at 20° C. for 3 hr. Upon completion as monitored by LCMS, the reaction mixture was diluted with water (20 mL) and extracted with EA (50 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 25 g SepaFlash® Silica Flash Column, Eluent of 0˜45% (Ethyl acetate:EtOH=4:1)/Petroleum ether gradient) to give Example 4 monomer (1.2 g, 38.2% yield) as a white solid. ESI-LCMS: 604.1 [M+H]⁺; ¹H NMR (400 MHz, CD₃CN) δ=1.12-1.24 (m, 12H) 2.61-2.77 (m, 2H) 3.43 (d, J=17.64 Hz, 3H) 3.59-3.69 (m, 2H) 3.71-3.78 (m, 6H) 3.79-4.14 (m, 5H) 4.16-4.28 (m, 1H) 4.29-4.42 (m, 1H) 5.59-5.72 (m, 1H) 5.89 (t, J=4.53 Hz, 1H) 7.48 (br d, J=12.76 Hz, 1H) 7.62-7.74 (m, 1H) 9.26 (br s, 1H); ³¹P NMR (162 MHz, CD₃CN) δ=150.57, 149.96, 9.87

Example 5: Synthesis of 5′ End Cap Monomer

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Example 5 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (30 g, 101.07 mmol, 87% purity) in CH₃CN (1.2 L) and Py (60 mL) were added 12 (33.35 g, 131.40 mmol, 26.47 mL) and PPh₃(37.11 g, 141.50 mmol) in one portion at 10° C. The reaction was stirred at 25° C. for 48 h. Upon completion, the mixture was diluted with saturated aq.Na₂S₂O₃(300 mL) and saturated aq.NaHCO₃(300 mL), concentrated to remove CH₃CN, and extracted with EtOAc (300 mL*3). The combined organic layers were washed with brine (300 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 330 g SepaFlash® Silica Flash Column, Eluent of 0˜60% Methanol/Dichloromethane gradient @ 100 mL/min) to give 2 (28.2 g, 72% yield) as a brown solid. ESI-LCMS: 369.1 [M+H]⁺; H NMR (400 MHz, DMSO-d₆) δ=11.43 (s, 1H), 7.68 (d, J=8.1 Hz, 1H), 5.86 (d, J=5.5 Hz, 1H), 5.69 (d, J=8.1 Hz, 1H), 5.46 (d, J=6.0 Hz, 1H), 4.08-3.96 (m, 2H), 3.90-3.81 (m, 1H), 3.60-3.51 (m, 1H), 3.40 (dd, J=6.9, 10.6 Hz, 1H), 3.34 (s, 3H).

Preparation of (3): To the solution of 2 (12 g, 32.6 mmol) in DCM (150 mL) were added AgNO₃(11.07 g, 65.20 mmol), 2,4,6-trimethylpyridine (11.85 g, 97.79 mmol, 12.92 mL), and DMTCl (22.09 g, 65.20 mmol) at 10° C., and the reaction mixture was stirred at 10° C. for 16 hr. Upon completion, the mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; 120 g SepaFlash® Silica Flash Column, Eluent of 0˜50% Ethyl acetate/Petroleum ether gradient @ 60 mL/min) to give 3 (17 g, 70.78% yield) as a yellow solid. ESI-LCMS: 693.1 [M+Na]⁺¹; H NMR (400 MHz, DMSO-d₆) δ=11.46 (s, 1H), 7.60 (d, J=8.4 Hz, 1H), 7.49 (d, J=7.2 Hz, 2H), 7.40-7.30 (m, 6H), 7.29-7.23 (m, 1H), 6.93 (d, J=8.8 Hz, 4H), 5.97 (d, J=6.0 Hz, 1H), 5.69 (d, J=8.0 Hz, 1H), 4.05-4.02 (m, 1H), 3.75 (d, J=1.2 Hz, 6H), 3.57 (t, J=5.6 Hz, 1H), 3.27 (s, 4H), 3.06 (t, J=10.4 Hz, 1H), 2.98-2.89 (m, 1H).

Preparation of (4): To a solution of 3 (17 g, 25.35 mmol) in DMF (200 mL) was added AcSK (11.58 g, 101.42 mmol) at 25° C., and the reaction was stirred at 60° C. for 2 hr. The mixture was diluted with H₂O (600 mL) and extracted with EtOAc (300 mL*4). The combined organic layers were washed with brine (300 mL), dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give 4 (15.6 g, crude) as a brown solid, which was used directly without further purification. ESI-LCMS: 641.3 [M+H]⁺.

Preparation of (5): To a solution of 4 (15.6 g, 25.21 mmol) in CH₃CN (200 mL) were added DTT (11.67 g, 75.64 mmol, 11.22 mL) and LiOH.H₂O (1.06 g, 25.21 mmol) at 10° C. under Ar. The reaction was stirred at 10° C. for 1 hr. The mixture was concentrated under reduced pressure to remove CH₃CN, and the residue was diluted with H₂O (400 mL) and extracted with EtOAc (200 mL*3). The combined organic layers were washed with brine (300 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 220 g SepaFlash® Silica Flash Column, Eluent of 0˜60% Ethyl acetate/Petroleum ether gradient @ 100 mL/min) to give 5 (8.6 g, 56.78% yield) as a white solid. ESI-LCMS: 599.3 [M+Na]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=8.79 (s, 1H), 7.61 (d, J=8.0 Hz, 1H), 7.56-7.46 (m, 2H), 7.45-7.37 (m, 4H), 7.36-7.27 (m, 3H), 6.85 (dd, J=2.8, 8.8 Hz, 4H), 5.85 (d, J=1.3 Hz, 1H), 5.68 (dd, J=2.0, 8.2 Hz, 1H), 4.33-4.29 (m, 1H), 3.91 (dd, J=4.8, 8.2 Hz, 1H), 3.81 (d, J=1.6 Hz, 6H), 3.33 (s, 3H), 2.85-2.80 (m, 1H), 2.67-2.55 (m, 2H), 1.11 (t, J=8.8 Hz, 1H).

Preparation of (Example 5 monomer): To a solution of 5 (6 g, 10.40 mmol) in DCM (120 mL) were added P1 (4.08 g, 13.53 mmol, 4.30 mL) and DCI (1.35 g, 11.45 mmol) in one portion at 10° C. under Ar. The reaction was stirred at 10° C. for 2 hr. The reaction mixture was diluted with saturated aq.NaHCO₃(50 mL) and extracted with DCM (20 mL*3). The combined organic layers were washed with brine (30 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: YMC-Triart Prep C18 250*50 mm*10 um; mobile phase: [water (10 mM NH₄HCO₃)-ACN]; B %: 35%-81%, 20 min) to give Example 5 monomer (3.54 g, 43.36% yield) as a yellow solid. ESI-LCMS: 776.4 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=7.65-7.38 (m, 7H), 7.37-7.22 (m, 3H), 6.90 (d, J=8.4 Hz, 4H), 5.92 (s, 1H), 5.66 (t, J=8.2 Hz, 1H), 4.13 (d, J=4.0 Hz, 1H), 4.00-3.88 (m, 1H), 3.87-3.59 (m, 10H), 3.33 (d, J=5.8 Hz, 3H), 3.12-2.94 (m, 1H), 2.78-2.60 (m, 3H), 2.55-2.48 (m, 1H), 1.36-0.98 (m, 12H); ³¹P NMR (162 MHz, DMSO-d₆) δ=162.69.

Example 6: Synthesis of 5′ End Cap Monomer

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Example 6 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (22.6 g, 45.23 mmol) in DCM (500 mL) and H₂O (125 mL) were added TEMPO (6.40 g, 40.71 mmol) and DIB (29.14 g, 90.47 mmol) at 0° C. The mixture was stirred at 20° C. for 20 h. Upon completion as monitored by LCMS, saturated aq. NaHCO₃was added to the mixture to adjust pH >8. The mixture was diluted with H₂O (200 mL) and washed with DCM (100 mL*3). The aqueous layer was collected, adjusted to pH<5 by HCl (4M), and extracted with DCM (200 mL*3). The combined organic layers were washed with brine (300 mL), dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give 2 (17.5 g, 68.55% yield) as a yellow solid. ESI-LCMS: 514.2 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=11.27 (s, 1H), 8.86 (s, 1H), 8.78 (s, 1H), 8.06 (d, J=7.5 Hz, 2H), 7.68-7.62 (m, 1H), 7.59-7.52 (m, 2H), 6.28 (d, J=6.8 Hz, 1H), 4.82-4.76 (m, 1H), 4.54 (dd, J=4.1, 6.7 Hz, 1H), 4.48 (d, J=1.8 Hz, 1H), 3.32 (s, 3H), 0.94 (s, 9H), 0.18 (d, J=4.8 Hz, 6H).

Preparation of (3): To a solution of 2 (9.3 g, 18.11 mmol) in MeOH (20 mL) was added SOCl₂(3.23 g, 27.16 mmol, 1.97 mL) dropwise at 0° C. The mixture was stirred at 20° C. for 0.5 hr. Upon completion as monitored by LCMS, the reaction mixture was quenched by addition of saturated aq. NaHCO₃(80 mL) and concentrated under reduced pressure to remove MeOH. The aqueous layer was extracted with DCM (80 mL*3). The combined organic layers were washed with brine (200 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 120 g SepaFlash® Silica Flash Column, Eluent of 0˜5%, MeOH/DCM gradient @ 85 mL/min) to give 3 (5.8 g, 60% yield) as a yellow solid. ESI-LCMS: 528.3 [M+H]⁺, ¹H NMR (400 MHz, DMSO-d₆) δ=11.28 (s, 1H), 8.79 (d, J=7.3 Hz, 2H), 8.06 (d, J=7.5 Hz, 2H), 7.68-7.62 (m, 1H), 7.60-7.53 (m, 2H), 6.28 (d, J=6.6 Hz, 1H), 4.87 (dd, J=2.4, 4.0 Hz, 1H), 4.61 (dd, J=4.3, 6.5 Hz, 1H), 4.57 (d, J=2.2 Hz, 1H), 3.75 (s, 3H), 3.32 (s, 3H), 0.94 (s, 9H), 0.17 (d, J=2.2 Hz, 6H).

Preparation of (4): To a mixture of 3 (5.7 g, 10.80 mmol) in CD₃OD (120 mL) was added NaBD₄(1.63 g, 43.21 mmol) in portions at 0° C., and the mixture was stirred at 20° C. for 1 hr. Upon completion as monitored by LCMS, the reaction mixture was neutralized by AcOH (˜10 mL) and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, Eluent of 0˜5%, MeOH/DCM gradient @ 40 mL/min) to give 4 (4.15 g, 7.61 mmol, 70.45% yield) as a yellow solid. ESI-LCMS: 502.2 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=11.23 (s, 1H), 8.76 (s, 2H), 8.04 (d, J=7.3 Hz, 2H), 7.69-7.62 (m, 1H), 7.60-7.52 (m, 2H), 6.14 (d, J=6.0 Hz, 1H), 5.18 (s, 1H), 4.60-4.51 (m, 2H), 3.98 (d, J=3.0 Hz, 1H), 3.32 (s, 3H), 0.92 (s, 9H), 0.13 (d, J=1.5 Hz, 6H).

Preparation of (5): To a solution of 4 (4.85 g, 9.67 mmol) in pyridine (50 mL) was added DMTrCl (5.90 g, 17.40 mmol) at 25° C. and the mixture was stirred for 2 hr. Upon completion as monitored by LCMS, the reaction mixture was concentrated under reduced pressure to remove pyridine. The residue was diluted with EtOAc (150 mL) and washed with H₂O (50 mL*3), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0˜70%, EA/PE gradient @ 60 mL/min) to give 5 (6.6 g, 84.06% yield) as a yellow solid. ESI-LCMS: 804.3[M+H]⁺, ¹H NMR (400 MHz, DMSO-d₆) δ=11.22 (s, 1H), 8.68 (d, J=11.0 Hz, 2H), 8.03 (d, J=7.3 Hz, 2H), 7.68-7.60 (m, 1H), 7.58-7.49 (m, 2H), 7.37-7.30 (m, 2H), 7.27-7.16 (m, 7H), 6.88-6.79 (m, 4H), 6.17 (d, J=4.2 Hz, 1H), 4.72 (t, J=5.0 Hz, 1H), 4.60 (t, J=4.5 Hz, 1H), 4.03-3.98 (m, 1H), 3.71 (s, 6H), 0.83 (s, 9H), 0.12-0.03 (m, 6H).

Preparation of (6): To a solution of 5 (6.6 g, 8.21 mmol) in THF (16 mL) was added TBAF (1 M, 8.21 mL,), and the mixture was stirred at 20° C. for 2 hr. Upon completion as monitored by LCMS, the reaction mixture was diluted with EA (150 mL) and washed with H₂O (50 mL*3). The organic layer was washed with brine (150 mL), dried over Na₂SO₄, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 10-100%, EA/PE gradient @ 30 mL/min) to give 6 (5.4 g, 94.4% yield) as a yellow solid. ESI-LCMS: 690.3 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=11.24 (s, 1H), 8.69 (s, 1H), 8.62 (s, 1H), 8.05 (d, J=7.3 Hz, 2H), 7.69-7.62 (m, 1H), 7.60-7.52 (m, 2H), 7.40-7.33 (m, 2H), 7.30-7.18 (m, 7H), 6.84 (dd, J=5.9, 8.9 Hz, 4H), 6.19 (d, J=4.8 Hz, 1H), 5.36 (d, J=6.0 Hz, 1H), 4.59-4.52 (m, 1H), 4.48 (q, J=5.1 Hz, 1H), 4.11 (d, J=4.8 Hz, 1H), 3.72 (d, J=1.0 Hz, 6H), 3.40 (s, 3H).

Preparation of (Example 6 monomer): To a solution of 6 (8.0 g, 11.60 mmol) in MeCN (150 mL) was added P-1 (4.54 g, 15.08 mmol, 4.79 mL) at 0° C., followed by DCI (1.51 g, 12.76 mmol) in one portion. The mixture was warmed to 20° C. and stirred for 2 h. Upon completion as monitored by LCMS, the reaction mixture was quenched by addition of saturated aq. NaHCO₃(50 mL) and diluted with DCM (250 mL). The organic layer was washed with saturated aq.NaHCO₃(50 mL*2), dried over Na₂SO₄, filtered and concentrated under reduced pressure. The residue was purified by a flash silica gel column (0% to 60% EA in PE contain 0.5% TEA) to give Example 6 monomer (5.75 g, 55.37% yield, 99.4% purity) as a white solid. ESI-LCMS: 890.4 [M+H]⁺; ¹H NMR (400 MHz, CD₃CN) δ=9.55 (s, 1H), 8.63-8.51 (m, 1H), 8.34-8.24 (m, 1H), 7.98 (br d, J=7.5 Hz, 2H), 7.65-7.55 (m, 1H), 7.53-7.46 (m, 2H), 7.44-7.37 (m, 2H), 7.32-7.17 (m, 7H), 6.84-6.77 (m, 4H), 6.14 (d, J=4.3 Hz, 1H), 4.84-4.73 (m, 1H), 4.72-4.65 (m, 1H), 4.34-4.27 (m, 1H), 3.91-3.61 (m, 9H), 3.50-3.43 (m, 3H), 2.72-2.61 (m, 1H), 2.50 (t, J=6.0 Hz, 1H), 1.21-1.15 (m, 10H), 1.09 (d, J=6.8 Hz, 2H); ³¹P NMR (162 MHz, CD₃CN) δ =150.01, 149.65

Example 7: Synthesis of 5′ End Cap Monomer

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Example 7 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (10 g, 27.22 mmol) in CH₃CN (200 mL) and H₂O (50 mL) were added TEMPO (3.85 g, 24.50 mmol) and DIB (17.54 g, 54.44 mmol). The mixture was stirred at 25° C. for 12 h. Upon completion as monitored by LCMS, the reaction mixture was concentrated under reduced pressure to give a residue. The residue was triturated with EtOAc (600 mL) for 30 min. The resulting suspension was filtered and the collected solid was washed with EtOAc (300 mL*2) to give 2 (20.09 g, 91.5% yield) as a white solid. ESI-LCMS: 382.0 [M+H]⁺.

Preparation of (3): To a solution of 2 (6 g, 15.73 mmol) in MeOH (100 mL) was added SOCl₂(2.81 g, 23.60 mmol, 1.71 mL) dropwise at 0° C. The mixture was stirred at 25° C. for 12 h. Upon completion as monitored by LCMS, the reaction mixture was quenched by addition of NaHCO₃(4 g) and stirred at 25° C. for 30 min. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to give 3 (18.8 g, 95.6% yield) as a white solid. The crude product was used for the next step without further purification. (The reaction was set up in parallel 3 batches and combined). ESI-LCMS: 396.1 [M+H]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=12.26-11.57 (m, 2H), 8.42-8.06 (m, 1H), 6.14-5.68 (m, 2H), 4.56 (s, 2H), 4.33 (dd, J=4.0, 7.3 Hz, 1H), 3.77 (m, 3H), 3.30 (s, 3H), 2.81-2.69 (m, 1H), 1.11 (s, 6H)

Preparation of (4 & 5): To a mixture of 3 (10.1 g, 25.55 mmol) in CD₃OD (120 mL) was added NaBD₄(3.29 g, 86.86 mmol, 3.4 eq) in portions at 0° C. The mixture was stirred at 25° C. for 1 h. Upon completion as monitored by LCMS, the reaction mixture was neutralized with AcOH (˜15 mL) and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 120 g SepaFlash® Silica Flash Column, Eluent of 0˜7.4%, MeOH/DCM gradient @ 80 mL/min) to give 4 (2.98 g, 6.88 mmol, 27% yield) as a yellow solid. ESI-LCMS: 370.1[M+H]⁺ and 5 (10.9 g, crude) as a yellow solid. ESI-LCMS: 300.1[M+H]⁺; ¹H NMR (400 MHz, CD₃OD) δ=7.85 (s, 1H), 5.87 (d, J=6.0 Hz, 1H), 4.46-4.39 (m, 1H), 4.34 (t, J=5.4 Hz, 1H), 4.08 (d, J=3.1 Hz, 1H), 3.49-3.38 (m, 4H)

Preparation of 6: To a solution of 4 (1.9 g, 4.58 mmol, 85.7% purity) in pyridine (19 mL) was added DMTrCl (2.02 g, 5.96 mmol). The mixture was stirred at 25° C. for 2 h under N₂. Upon completion as monitored by LCMS, the reaction mixture was quenched by MeOH (10 mL) and concentrated under reduce pressure to give a residue. The residue was diluted with H₂O (10 mL*3) and extracted with EA (20 mL*3). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na₂SO₄, filtered and concentrated under reduce pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 25 g SepaFlash® Silica Flash Column, Eluent of 0˜77%, PE: (EA with 10% EtOH): 1% TEA@ 35 mL/min) to give 6 (2.6 g, 81.71% yield, 96.71% purity) as a white foam. ESI-LCMS: 672.2 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=12.02 (s, 1H), 7.96 (s, 1H), 7.83 (s, 1H), 7.51 (d, J=7.4 Hz, 2H), 7.37 (d, J=8.6 Hz, 4H), 7.25-7.17 (m, 2H), 6.80 (t, J=8.4 Hz, 4H), 5.88 (d, J=6.3 Hz, 1H), 4.69 (t, J=5.7 Hz, 1H), 4.64 (s, 1H), 4.54 (s, 1H), 4.19 (d, J=2.9 Hz, 1H), 3.77 (d, J=4.5 Hz, 6H), 3.60-3.38 (m, 3H), 2.81 (s, 1H), 1.81 (td, J=6.9, 13.7 Hz, 1H), 0.97 (d, J=6.8 Hz, 3H), 0.80 (d, J=6.9 Hz, 3H)

Preparation of Example 7 monomer: To a solution of 6 (8.4 g, 12.5 mmol) in MeCN (80 mL) was added P-1 (4.9 g, 16.26 mmol, 5.16 mL) at 0° C., followed by addition of DCI (1.624 g, 13.76 mmol) in one portion at 0° C. under Ar. The mixture was stirred at 25° C. for 2 h. Upon completion as monitored by LCMS, the reaction mixture was quenched with saturated aq.NaHCO₃(20 mL) and extracted with DCM (50 mL*2). The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated under reduce pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, Eluent of 0˜52% PE: EA (10% EtOH): 5% TEA, @ 80 mL/min) to give Example 7 monomer (3.4 g, 72.1% yield,) as a white foam. ESI-LCMS: 872.4 [M+H]⁺; ¹H NMR (400 MHz, CD₃CN) δ=12.46-11.07 (m, 1H), 9.29 (s, 1H), 7.84 (d, J=14.6 Hz, 1H), 7.42 (t, J=6.9 Hz, 2H), 7.34-7.17 (m, 7H), 6.85-6.77 (m, 4H), 5.95-5.77 (m, 1H), 4.56-4.40 (m, 2H), 4.24 (dd, J=4.0, 13.3 Hz, 1H), 3.72 (d, J=2.0 Hz, 7H), 3.66-3.53 (m, 3H), 3.42 (d, J=11.8 Hz, 3H), 2.69-2.61 (m, 1H), 2.60-2.42 (m, 2H), 1.16-1.00 (m, 18H); ³¹P NMR (162 MHz, CD₃CN) δ=149.975, 149.9

Example 8: Synthesis of 5′ End Cap Monomer

embedded image

Example 8 Monomer Synthesis Scheme

Preparation of (2): To a solution of 1 (40 g, 58.16 mmol) in DMF (60 mL) were added imidazole (11.88 g, 174.48 mmol), NaI (13.08 g, 87.24 mmol), and TBSCl (17.52 g, 116.32 mmol) at 20° C. in one portion. The reaction mixture was stirred at 20° C. for 12 h. Upon completion, the mixture was diluted with EA (200 mL). The organic layer was washed with brine/water (80 mL/80 mL*4), dried over Na₂SO₄, filtered and evaporated to give 2 (50.8 g, crude) as yellow solid. ESI-LCMS: 802.3 [M+H]⁺

Preparation of (3): To a solution of 2 (8.4 g, 10.47 mmol) in DCM (120 mL) were added Et₃SiH (3.06 g, 26.3 mmol, 4.2 mL) and TFA (1.29 g, 0.84 mL) dropwise at 0° C. The reaction mixture was stirred at 20° C. for 2 h. The reaction mixture was washed with saturated aq.NaHCO₃(15 mL) and brine (80 mL). The organic layer was dried over Na₂SO₄, filtered and evaporated. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0˜83% EA/PE gradient @ 80 mL/min) to give 3 (2.92 g, 55.8% yield,) as a white solid. ESI-LCMS: 500.2 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=8.79 (s, 1H), 8.14 (s, 1H), 8.02 (d, J=7.6 Hz, 2H), 7.64-7.58 (m, 1H), 7.56-7.49 (m, 2H), 5.98-5.93 (m, 1H), 4.63-4.56 (m, 2H), 4.23 (s, 1H), 3.98 (dd, J=1.5, 13.1 Hz, 1H), 3.75 (dd, J=1.5, 13.1 Hz, 1H), 3.28 (s, 3H), 2.06-1.99 (m, 1H), 1.00-0.90 (m, 9H), 0.15 (d, J=7.0 Hz, 6H).

Preparation of (4): 3 (6 g, 12.01 mmol) and tert-butyl N-methylsulfonylcarbamate (3.52 g, 18.01 mmol) were co-evaporated with toluene (50 mL), dissolved in dry THF (100 mL), and cooled to 0° C. PPh₃(9.45 g, 36.03 mmol,) was then added, followed by dropwise addition of DIAD (7.28 g, 36.03 mmol, 7.00 mL) in dry THF (30 mL). The reaction mixture was stirred at 20° C. for 18 h. Upon completion, the reaction mixture was then diluted with DCM (100 mL) and washed with water (70 mL) and brine (70 mL), dried over Na₂SO₄, filtered and evaporated to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 80 g SepaFlash® Silica Flash Column, Eluent of 0˜100% Ethyl acetate/Petroleum ether gradient @ 60 mL/min) followed by reverse-phase HPLC (0.1% NH₃.H₂O condition, eluent at 74%) to give 4 (2.88 g, 25% yield) as a white solid. ESI-LCMS: 677.1 [M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=9.24 (s, 1H), 8.84 (s, 1H), 8.36 (s, 1H), 8.05 (br d, J=7.3 Hz, 2H), 7.66-7.42 (m, 4H), 6.16 (d, J=5.0 Hz, 1H), 4.52 (br t, J=4.5 Hz, 1H), 4.25-4.10 (m, 1H), 3.97 (br dd, J=8.0, 14.8 Hz, 1H), 3.48 (s, 3H), 3.27 (s, 3H), 1.54 (s, 9H), 0.95 (s, 9H), 0.14 (d, J=0.8 Hz, 6H).

Preparation of (5): To a solution of 4 (2.8 g, 4.14 mmol) in THF (20 mL) was added TBAF (4 M, 1.03 mL) and the mixture was stirred at 20° C. for 12 h. The reaction mixture was then evaporated. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜6% MeOH/ethyl acetate gradient @ 20 mL/min) to give 5 (2.1 g, 83.92% yield) as a white solid. ESI-LCMS: 563.1[M+H]⁺; ¹H NMR (400 MHz, CDCl₃) δ=8.85-8.77 (m, 1H), 8.38 (s, 1H), 8.11-7.99 (m, 2H), 7.64-7.50 (m, 4H), 6.19 (d, J=2.8 Hz, 1H), 4.36-4.33 (m, 1H), 4.29 (br d, J=4.3 Hz, 1H), 4.22-4.02 (m, 2H), 3.65-3.59 (m, 3H), 3.28 (s, 3H), 1.54 (s, 9H).

Preparation of (6): To a solution of 5 (2.1 g, 3.73 mmol) in DCM (20 mL) was added TFA (7.70 g, 67.53 mmol, 5 mL) at 0° C. The reaction mixture was stirred at 20° C. for 24 h. Upon completion, the reaction was quenched with saturated aq. NaHCO₃to reach pH 7. The organic layer was dried over Na₂SO₄, filtered, and evaporated at low pressure. The residue was purified by flash silica gel chromatography (ISCO®; 12 g SepaFlash® Silica Flash Column, Eluent of 0˜7% DCM/MeOH gradient @ 20 mL/min) to give 1.6 g (impure, 75% LCMS purity), followed by prep-HPLC [FA condition, column: Boston Uni C18 40*150*5 um; mobile phase: [water (0.225% FA)-ACN]; B %: 8%-38%, 7.7 min.] to give 6 (1.04 g, 63.7% yield) as a white solid. ESI-LCMS: 485.0 [M+Na]⁺; ¹H NMR (400 MHz, DMSO-d₆) δ=11.27-11.21 (m, 1H), 8.77 (s, 1H), 8.74 (s, 1H), 8.05 (d, J=7.3 Hz, 2H), 7.68-7.62 (m, 1H), 7.59-7.53 (m, 2H), 7.39 (t, J=6.3 Hz, 1H), 6.16 (d, J=6.0 Hz, 1H), 5.48 (d, J=5.5 Hz, 1H), 4.55 (t, J=5.5 Hz, 1H), 4.43-4.37 (m, 1H), 4.08-4.02 (m, 1H), 3.41-3.36 (m, 1H), 3.35 (s, 3H), 3.31-3.22 (m, 1H), 2.91 (s, 3H).

Preparation of (Example 8 monomer): To a solution of 6 (1 g, 2.16 mmol) in DCM (30 mL) was added P1 (977.58 mg, 3.24 mmol, 1.03 mL), followed by DCI (306.43 mg, 2.59 mmol) at 0° C. in one portion under Ar atmosphere. The mixture was degassed and purged with Ar for 3 times, warmed to 20° C., and stirred for 2 hr under Ar atmosphere. Upon completion as monitored by LCMS and TLC (PE:EtOAc=4:1), the reaction mixture was diluted with sat.aq. NaHCO₃(30 mL) and extracted with DCM (50 mL*2). The combined organic layers were dried over anhydrous Na₂SO₄, filtered, and the filtrate was concentrated under reduced pressure to give a residue. The crude product was purified by reversed-phase HPLC (40 g C18 column: neutral condition, Eluent of 0˜57% of 0.3% NH₄HCO₃in H₂O/CH₃CN ether gradient @ 35 mL/min) to give Example 8 monomer (0.49 g, 33.7% yield) as a white solid. ESI-LCMS: 663.1[M+H]⁺; ¹H NMR (400 MHz, CD₃CN) δ=1.19-1.29 (m, 12H) 2.71 (q, J=5.77 Hz, 2H) 2.94 (d, J=6.27 Hz, 3H) 3.35 (d, J=15.56 Hz, 3H) 3.40-3.52 (m, 2H) 3.61-3.97 (m, 4H) 4.23-4.45 (m, 1H) 4.55-4.74 (m, 2H) 6.02 (dd, J=10.67, 6.40 Hz, 1H) 7.25 (br s, 1H) 7.47-7.57 (m, 2H) 7.59-7.68 (m, 1H) 8.01 (d, J=7.78 Hz, 2H) 8.28 (s, 1H) 8.66 (s, 1H) 9.69 (br s, 1H); ³¹P NMR (162 MHz, CD₃CN) δ=150.92, 149.78.

Example 9: Synthesis of 5′-stabilized End Cap Modified Oligonucleotides

This example provides an exemplary method for synthesizing the siNAs comprising a 5′-stabilized end caps disclosed herein. The 5′-stabilized end cap and/or deuterated phosphoramidites were dissolved in anhydrous acetonitrile and oligonucleotide synthesis was performed on a Expedite 8909 Synthesizer using standard phosphoramidite chemistry. An extended coupling (12 minutes) of 0.12 M solution of phosphoramidite in anhydrous CH₃CN in the presence of Benzyl-thio-tetrazole (BTT) activator to a solid bound oligonucleotide followed by standard capping, oxidation and sulfurization produced modified oligonucleotides. The 0.02 M 12, THE: Pyridine; Water 7:2:1 was used as an oxidizing agent, while DDTT (dimethylamino-methylidene) amino)-3H-1,2,4-dithiazaoline-3-thione was used as the sulfur-transfer agent for the synthesis of oligoribonucleotide with a phosphorothioate backbone. The stepwise coupling efficiency of all modified phosphoramidites was achieved around 98%. After synthesis the solid support was heated with aqueous ammonia (28%) solution at 45° C. for 16 h or 0.05 M K₂CO₃in methanol was used to deprotect the base labile protecting groups. The crude oligonucleotides were precipitated with isopropanol and centrifuged (Eppendorf 5810R, 3000 g, 4° C., 15 min) to obtain a pellet. The crude product was then purified using ion exchange chromatography (TSK gel column, 20 mM NaH₂PO₄, 10% CH₃CN, 1 M NaBr, gradient 20-60% B over 20 column volumes) and fractions were analyzed by ion change chromatography on an HPLC. Pure fractions were pooled and desalted by Sephadex G-25 column and evaporated to dryness. The purity and molecular weight were determined by HPLC analysis and ESI-MS analysis. Single strand RNA oligonucleotides (sense and antisense strand) were annealed (1:1 by molar equivalents) at 90° C. for 3 min followed by RT 40 min) to produce the duplexes.

Example 10: SARS-CoV-2-Nanoluc Antiviral Assay in Human ACE-2 Expressing A549 Cells

The assay has been modified from Xie X et al., 2020, Nature Communications, doi.org/10.1038/s41467-020-19055-7.

A549 cells stably expressing human ACE2 were grown in culture medium consisting of high-glucose DMEM supplemented with 10% fetal bovine serum, 1% penicillin/streptomycin, 1% HEPES and 10 μg/mL Blasticidin S. Cells were grown at 37° C. with 5% CO₂. All culture medium and antibiotics were purchased from ThermoFisher Scientific (Waltham, Mass.). SARS-CoV-2-Nluc virus was generated through inserting the nanoluciferase gene into the ORF7 gene of the infectious cDNA clone SARS-CoV-2 virus (strain 2019-nCoV/USA_WA1/2020). For SARS-CoV-2-Nluc antiviral assay, A549-hACE2 cells (12,000 cells per well in 50 ul phenol-red free medium containing 2% FBS) were plated into white opaque 96-well plate (purchased from Corning, Corning, N.Y.). On the next day, 50 ul SARS-CoV-2-Nluc virus (MOI 0.08) was added to the cells, and incubated at 37° C. with 5% CO₂for 3 hours. Oligonucleotides were diluted in Opti-MEM medium and mixed with equal volume of diluted transfection reagent RNAiMaX (0.2 ul/well) (ThermoFisher). The transfection mixture was incubated at room temperature for 10 mins and then added to cell plate at 3 hr post infection (20 ul/well). 48 hr post infection, 60 μL Nano luciferase substrate (Promega<Madison, Wis.) were added to each well. Luciferase signals were measured using a Synergy™ Neo2 microplate reader (BioTek, Winooski, Vt.). Antiviral % inhibition was calculated as follows: [(Oligonucleotide treated cells infected sample)−(no oligonucleotide infected control)]/[(Uninfected control)−(no oligonucleotide infected control)]*100; Using GraphPad (San Diego, Calif.) prism software version 8.3.1, the antiviral dose-response plot was generated as a sigmoidal fit, log(inhibitor) vs response-variable slope (four parameters) model and the EC₅₀was calculated which is the predicted oligonucleotide concentration corresponding to a 50% inhibition of the viral cytopathic effect.

Results for siNA assessed with this assay are shown in Table 4 at the end of the specification in column labeled “SARS-CoV-2 nanoluc hACE-2 A549 assay”.

Example 11: Three Concentration Reporter Plasmid Luciferase and Cytotoxicity Assay in COS-7 Cells

COS-7 monkey fibroblast cells (ATCC, CRL-1651) were seeded into 96-well culture plates at 15.0×10⁴cells/well and cultured in Dulbecco's Modified Eagle's Medium (DMEM; Hyclone, SH30022) supplemented with 10% fetal bovine serum (FBS; Sigma-Aldrich, F4135) and 1% Penicillin-Streptomycin (P/S; Corning, 30-002-CI) at 37° C. and 5% CO₂. After 6 hrs of incubation, cells were transiently transfected with psiCHECK2-SARS-CoV-2 plasmid (custom-synthesized by Genscript) at 50 ng/well using 0.3 μL of Lipofectamine 3000 transfection reagent (1:1 reagent/psi-CHECK2-SARS-CoV-2 DNA ratio; Invitrogen) in Opti-MEM (Invitrogen, 11058-021) according to the manufacturer's protocol. After overnight incubation, the medium was removed and replaced with 100 ul fresh growth media. Test siRNAs along with appropriate controls (Ambion siRNAs, ThermoFisher) were diluted to final concentration of 1, 10 or 100 nM in Opti-MEM (Invitrogen, 11058-021). Cells were then transfected with test siRNAs in duplicates using 0.3 ul/well RNAiMAX transfection reagent (1:1 ratio; Invitrogen) according to the manufacturer's protocol. After approximately 48 hrs, the culture plates were equilibrated to RT, 100 μL of Dual-Luciferase Reporter Assay reagent (Promega, E6120) were added to each well according to manufacturer's protocol. Luminescence was measured on an Envision plate reader (Perkin Elmer). The results were then quantified by calculating the ratio of renilla to firefly luciferase expression for each of the duplicates and reported as percent inhibition of luciferase activity relative to no-drug control (mock transfection with psiCHECK2-SARS-CoV-2 plasmid). The assay was repeated with a different set of plates and cytotoxicity of test siRNAs was assessed 48 hrs post treatment of COS-7 cells. The cells were lysed and assayed with Cell-Titer Glo reagent (Promega) according to the manufacturer's protocol.

Results for siNA assessed with this assay are shown in Table 4 at the end of the specification in column labeled “pSiCHECK-2 reporter assay Cos-7 at least 50% inhibition”. The data was reported as % viability relative to no-drug control (mock transfection with psiCHECK2-SARS-CoV-2 plasmid).

Example 12: Reporter Plasmid Luciferase and Cytotoxicity Assay in Cos7 Cells

COS-7 monkey fibroblast cells (ATCC, CRL-1651) were seeded into 96-well culture plates at 15.0×10⁴cells/well and cultured in Dulbecco's Modified Eagle's Medium (DMEM; Hyclone, SH30022) supplemented with 10% fetal bovine serum (FBS; Sigma-Aldrich, F4135) and 1% Penicillin-Streptomycin (P/S; Corning, 30-002-CI) at 37° C. and 5% CO₂. After 6 hrs of incubation, cells were transiently transfected with psiCHECK2-SARS-CoV-2 plasmid (custom-synthesized by Genscript) at 50 ng/well using 0.3 μL of Lipofectamine 3000 transfection reagent (1:1 reagent/psi-CHECK2-SARS-CoV-2 DNA ratio; Invitrogen) in Opti-MEM (Invitrogen, 11058-021) according to the manufacturer's protocol. After overnight incubation, the medium was removed and replaced with 100 ul fresh growth media. Test siRNAs along with appropriate controls (Ambion siRNAs, ThermoFisher) were serially diluted in Opti-MEM (Invitrogen, 11058-021). Cells were then transfected with test siRNAs in duplicates using 0.3 ul/well RNAiMAX transfection reagent (1:1 ratio; Invitrogen) according to the manufacturer's protocol. After approximately 48 hrs, the culture plates were equilibrated to RT, 100 μL of Dual-Luciferase Reporter Assay reagent (Promega, E6120) were added to each well according to manufacturer's protocol. Luminescence was measured on an Envision plate reader (Perkin Elmer). The results were then quantified by calculating the ratio of renilla to firefly luciferase expression for each of the duplicates and reported as percent inhibition of luciferase activity relative to no-drug control (mock transfection with psiCHECK2-SARS-CoV-2 plasmid) and dose-response curves were fitted by non-linear regression with variable slope (four parameters). Statistical analysis was performed in GraphPad Prism 8.3.1 (San Diego, Calif.) and the EC₅₀was calculated which is the predicted oligonucleotide concentration corresponding to a 50% inhibition of the luciferase activity. The assay was repeated with a different set of plates and cytotoxicity of test siRNAs was assessed 48 hrs post treatment of COS-7 cells. The cells were lysed and assayed with Cell-Titer Glo reagent (Promega) according to the manufacturer's protocol.

Results for siNA assessed with this assay are shown in Table 4 at the end of the specification in column labeled “pSiCHECK-2 reporter assay Cos-7”. The data was reported as % viability relative to no-drug control (mock transfection with psiCHECK2-SARS-CoV-2 plasmid) and dose-response curves were fitted by non-linear regression with variable slope (four parameters) using GraphPad prism software version 8.3.1.

All patents and publications mentioned in the specification are indicative of the levels of those of ordinary skill in the art to which the disclosure pertains. All patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.

Further, one skilled in the art readily appreciates that the present disclosure is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein. Modifications therein and other uses will occur to those skilled in the art. These modifications are encompassed within the spirit of the disclosure and are defined by the scope of the claims, which set forth non-limiting embodiments of the disclosure.

TABLE 1

Oligonucleotide Target Sequences

SEQ
Target
SEQ
Target reverse

Start on
End on
ID
forward sequence
ID
complement sequence

Alias
target
target
NO
(sense strand)
NO
(antisense strand)

19-Mer Target Sequences

NC_045512.2_19mer_win1_00190
190
208
1
CTGCTTACGGTTTCGTCCG
1204
CGGACGAAACCGTAAGCAG

NC_045512.2_19mer_win1_00191
191
209
2
TGCTTACGGTTTCGTCCGT
1205
ACGGACGAAACCGTAAGCA

NC_045512.2_19mer_win1_00192
192
210
3
GCTTACGGTTTCGTCCGTG
1206
CACGGACGAAACCGTAAGC

NC_045512.2_19mer_win1_00193
193
211
4
CTTACGGTTTCGTCCGTGT
1207
ACACGGACGAAACCGTAAG

NC_045512.2_19mer_win1_00194
194
212
5
TTACGGTTTCGTCCGTGTT
1208
AACACGGACGAAACCGTAA

NC_045512.2_19mer_win1_00195
195
213
6
TACGGTTTCGTCCGTGTTG
1209
CAACACGGACGAAACCGTA

NC_045512.2_19mer_win1_00196
196
214
7
ACGGTTTCGTCCGTGTTGC
1210
GCAACACGGACGAAACCGT

NC_045512.2_19mer_win1_00197
197
215
8
CGGTTTCGTCCGTGTTGCA
1211
TGCAACACGGACGAAACCG

NC_045512.2_19mer_win1_00198
198
216
9
GGTTTCGTCCGTGTTGCAG
1212
CTGCAACACGGACGAAACC

NC_045512.2_19mer_win1_00233
233
251
10
CTAGGTTTCGTCCGGGTGT
1213
ACACCCGGACGAAACCTAG

NC_045512.2_19mer_win1_00234
234
252
11
TAGGTTTCGTCCGGGTGTG
1214
CACACCCGGACGAAACCTA

NC_045512.2_19mer_win1_00235
235
253
12
AGGTTTCGTCCGGGTGTGA
1215
TCACACCCGGACGAAACCT

NC_045512.2_19mer_win1_00236
236
254
13
GGTTTCGTCCGGGTGTGAC
1216
GTCACACCCGGACGAAACC

NC_045512.2_19mer_win1_00237
237
255
14
GTTTCGTCCGGGTGTGACC
1217
GGTCACACCCGGACGAAAC

NC_045512.2_19mer_win1_00238
238
256
15
TTTCGTCCGGGTGTGACCG
1218
CGGTCACACCCGGACGAAA

NC_045512.2_19mer_win1_00239
239
257
16
TTCGTCCGGGTGTGACCGA
1219
TCGGTCACACCCGGACGAA

NC_045512.2_19mer_win1_00240
240
258
17
TCGTCCGGGTGTGACCGAA
1220
TTCGGTCACACCCGGACGA

NC_045512.2_19mer_win1_00241
241
259
18
CGTCCGGGTGTGACCGAAA
1221
TTTCGGTCACACCCGGACG

NC_045512.2_19mer_win1_00242
242
260
19
GTCCGGGTGTGACCGAAAG
1222
CTTTCGGTCACACCCGGAC

NC_045512.2_19mer_win1_00243
243
261
20
TCCGGGTGTGACCGAAAGG
1223
CCTTTCGGTCACACCCGGA

NC_045512.2_19mer_win1_00244
244
262
21
CCGGGTGTGACCGAAAGGT
1224
ACCTTTCGGTCACACCCGG

NC_045512.2_19mer_win1_00245
245
263
22
CGGGTGTGACCGAAAGGTA
1225
TACCTTTCGGTCACACCCG

NC_045512.2_19mer_win1_00246
246
264
23
GGGTGTGACCGAAAGGTAA
1226
TTACCTTTCGGTCACACCC

NC_045512.2_19mer_win1_00247
247
265
24
GGTGTGACCGAAAGGTAAG
1227
CTTACCTTTCGGTCACACC

NC_045512.2_19mer_win1_00248
248
266
25
GTGTGACCGAAAGGTAAGA
1228
TCTTACCTTTCGGTCACAC

NC_045512.2_19mer_win1_00249
249
267
26
TGTGACCGAAAGGTAAGAT
1229
ATCTTACCTTTCGGTCACA

NC_045512.2_19mer_win1_00250
250
268
27
GTGACCGAAAGGTAAGATG
1230
CATCTTACCTTTCGGTCAC

NC_045512.2_19mer_win1_00251
251
269
28
TGACCGAAAGGTAAGATGG
1231
CCATCTTACCTTTCGGTCA

NC_045512.2_19mer_win1_00252
252
270
29
GACCGAAAGGTAAGATGGA
1232
TCCATCTTACCTTTCGGTC

NC_045512.2_19mer_win1_00253
253
271
30
ACCGAAAGGTAAGATGGAG
1233
CTCCATCTTACCTTTCGGT

NC_045512.2_19mer_win1_00254
254
272
31
CCGAAAGGTAAGATGGAGA
1234
TCTCCATCTTACCTTTCGG

NC_045512.2_19mer_win1_00255
255
273
32
CGAAAGGTAAGATGGAGAG
1235
CTCTCCATCTTACCTTTCG

NC_045512.2_19mer_win1_00256
256
274
33
GAAAGGTAAGATGGAGAGC
1236
GCTCTCCATCTTACCTTTC

NC_045512.2_19mer_win1_00257
257
275
34
AAAGGTAAGATGGAGAGCC
1237
GGCTCTCCATCTTACCTTT

NC_045512.2_19mer_win1_00258
258
276
35
AAGGTAAGATGGAGAGCCT
1238
AGGCTCTCCATCTTACCTT

NC_045512.2_19mer_win1_00259
259
277
36
AGGTAAGATGGAGAGCCTT
1239
AAGGCTCTCCATCTTACCT

NC_045512.2_19mer_win1_00260
260
278
37
GGTAAGATGGAGAGCCTTG
1240
CAAGGCTCTCCATCTTACC

NC_045512.2_19mer_win1_00261
261
279
38
GTAAGATGGAGAGCCTTGT
1241
ACAAGGCTCTCCATCTTAC

NC_045512.2_19mer_win1_00288
288
306
39
TCAACGAGAAAACACACGT
1242
ACGTGTGTTTTCTCGTTGA

NC_045512.2_19mer_win1_00289
289
307
40
CAACGAGAAAACACACGTC
1243
GACGTGTGTTTTCTCGTTG

NC_045512.2_19mer_win1_00290
290
308
41
AACGAGAAAACACACGTCC
1244
GGACGTGTGTTTTCTCGTT

NC_045512.2_19mer_win1_00291
291
309
42
ACGAGAAAACACACGTCCA
1245
TGGACGTGTGTTTTCTCGT

NC_045512.2_19mer_win1_00292
292
310
43
CGAGAAAACACACGTCCAA
1246
TTGGACGTGTGTTTTCTCG

NC_045512.2_19mer_win1_00293
293
311
44
GAGAAAACACACGTCCAAC
1247
GTTGGACGTGTGTTTTCTC

NC_045512.2_19mer_win1_00294
294
312
45
AGAAAACACACGTCCAACT
1248
AGTTGGACGTGTGTTTTCT

NC_045512.2_19mer_win1_00295
295
313
46
GAAAACACACGTCCAACTC
1249
GAGTTGGACGTGTGTTTTC

NC_045512.2_19mer_win1_00296
296
314
47
AAAACACACGTCCAACTCA
1250
TGAGTTGGACGTGTGTTTT

NC_045512.2_19mer_win1_00297
297
315
48
AAACACACGTCCAACTCAG
1251
CTGAGTTGGACGTGTGTTT

NC_045512.2_19mer_win1_00298
298
316
49
AACACACGTCCAACTCAGT
1252
ACTGAGTTGGACGTGTGTT

NC_045512.2_19mer_win1_00299
299
317
50
ACACACGTCCAACTCAGTT
1253
AACTGAGTTGGACGTGTGT

NC_045512.2_19mer_win1_00300
300
318
51
CACACGTCCAACTCAGTTT
1254
AAACTGAGTTGGACGTGTG

NC_045512.2_19mer_win1_00301
301
319
52
ACACGTCCAACTCAGTTTG
1255
CAAACTGAGTTGGACGTGT

NC_045512.2_19mer_win1_00302
302
320
53
CACGTCCAACTCAGTTTGC
1256
GCAAACTGAGTTGGACGTG

NC_045512.2_19mer_win1_00303
303
321
54
ACGTCCAACTCAGTTTGCC
1257
GGCAAACTGAGTTGGACGT

NC_045512.2_19mer_win1_00304
304
322
55
CGTCCAACTCAGTTTGCCT
1258
AGGCAAACTGAGTTGGACG

NC_045512.2_19mer_win1_00305
305
323
56
GTCCAACTCAGTTTGCCTG
1259
CAGGCAAACTGAGTTGGAC

NC_045512.2_19mer_win1_00306
306
324
57
TCCAACTCAGTTTGCCTGT
1260
ACAGGCAAACTGAGTTGGA

NC_045512.2_19mer_win1_00455
455
473
58
CTTGAACAGCCCTATGTGT
1261
ACACATAGGGCTGTTCAAG

NC_045512.2_19mer_win1_00456
456
474
59
TTGAACAGCCCTATGTGTT
1262
AACACATAGGGCTGTTCAA

NC_045512.2_19mer_win1_00457
457
475
60
TGAACAGCCCTATGTGTTC
1263
GAACACATAGGGCTGTTCA

NC_045512.2_19mer_win1_00458
458
476
61
GAACAGCCCTATGTGTTCA
1264
TGAACACATAGGGCTGTTC

NC_045512.2_19mer_win1_00459
459
477
62
AACAGCCCTATGTGTTCAT
1265
ATGAACACATAGGGCTGTT

NC_045512.2_19mer_win1_00626
626
644
63
GTTCTTCTTCGTAAGAACG
1266
CGTTCTTACGAAGAAGAAC

NC_045512.2_19mer_win1_00627
627
645
64
TTCTTCTTCGTAAGAACGG
1267
CCGTTCTTACGAAGAAGAA

NC_045512.2_19mer_win1_00628
628
646
65
TCTTCTTCGTAAGAACGGT
1268
ACCGTTCTTACGAAGAAGA

NC_045512.2_19mer_win1_00629
629
647
66
CTTCTTCGTAAGAACGGTA
1269
TACCGTTCTTACGAAGAAG

NC_045512.2_19mer_win1_00630
630
648
67
TTCTTCGTAAGAACGGTAA
1270
TTACCGTTCTTACGAAGAA

NC_045512.2_19mer_win1_00631
631
649
68
TCTTCGTAAGAACGGTAAT
1271
ATTACCGTTCTTACGAAGA

NC_045512.2_19mer_win1_00632
632
650
69
CTTCGTAAGAACGGTAATA
1272
TATTACCGTTCTTACGAAG

NC_045512.2_19mer_win1_00633
633
651
70
TTCGTAAGAACGGTAATAA
1273
TTATTACCGTTCTTACGAA

NC_045512.2_19mer_win1_00704
704
722
71
GACGAGCTTGGCACTGATC
1274
GATCAGTGCCAAGCTCGTC

NC_045512.2_19mer_win1_00705
705
723
72
ACGAGCTTGGCACTGATCC
1275
GGATCAGTGCCAAGCTCGT

NC_045512.2_19mer_win1_03352
3352
3370
73
TGGTTATTTAAAACTTACT
1276
AGTAAGTTTTAAATAACCA

NC_045512.2_19mer_win1_03353
3353
3371
74
GGTTATTTAAAACTTACTG
1277
CAGTAAGTTTTAAATAACC

NC_045512.2_19mer_win1_03354
3354
3372
75
GTTATTTAAAACTTACTGA
1278
TCAGTAAGTTTTAAATAAC

NC_045512.2_19mer_win1_03355
3355
3373
76
TTATTTAAAACTTACTGAC
1279
GTCAGTAAGTTTTAAATAA

NC_045512.2_19mer_win1_03356
3356
3374
77
TATTTAAAACTTACTGACA
1280
TGTCAGTAAGTTTTAAATA

NC_045512.2_19mer_win1_03357
3357
3375
78
ATTTAAAACTTACTGACAA
1281
TTGTCAGTAAGTTTTAAAT

NC_045512.2_19mer_win1_03358
3358
3376
79
TTTAAAACTTACTGACAAT
1282
ATTGTCAGTAAGTTTTAAA

NC_045512.2_19mer_win1_03359
3359
3377
80
TTAAAACTTACTGACAATG
1283
CATTGTCAGTAAGTTTTAA

NC_045512.2_19mer_win1_03360
3360
3378
81
TAAAACTTACTGACAATGT
1284
ACATTGTCAGTAAGTTTTA

NC_045512.2_19mer_win1_05384
5384
5402
82
GCTGCTAACTTTTGTGCAC
1285
GTGCACAAAAGTTAGCAGC

NC_045512.2_19mer_win1_05385
5385
5403
83
CTGCTAACTTTTGTGCACT
1286
AGTGCACAAAAGTTAGCAG

NC_045512.2_19mer_win1_06406
6406
6424
84
CTCTGAAGAAGTAGTGGAA
1287
TTCCACTACTTCTTCAGAG

NC_045512.2_19mer_win1_06407
6407
6425
85
TCTGAAGAAGTAGTGGAAA
1288
TTTCCACTACTTCTTCAGA

NC_045512.2_19mer_win1_06408
6408
6426
86
CTGAAGAAGTAGTGGAAAA
1289
TTTTCCACTACTTCTTCAG

NC_045512.2_19mer_win1_06409
6409
6427
87
TGAAGAAGTAGTGGAAAAT
1290
ATTTTCCACTACTTCTTCA

NC_045512.2_19mer_win1_06410
6410
6428
88
GAAGAAGTAGTGGAAAATC
1291
GATTTTCCACTACTTCTTC

NC_045512.2_19mer_win1_06411
6411
6429
89
AAGAAGTAGTGGAAAATCC
1292
GGATTTTCCACTACTTCTT

NC_045512.2_19mer_win1_06412
6412
6430
90
AGAAGTAGTGGAAAATCCT
1293
AGGATTTTCCACTACTTCT

NC_045512.2_19mer_win1_06413
6413
6431
91
GAAGTAGTGGAAAATCCTA
1294
TAGGATTTTCCACTACTTC

NC_045512.2_19mer_win1_06414
6414
6432
92
AAGTAGTGGAAAATCCTAC
1295
GTAGGATTTTCCACTACTT

NC_045512.2_19mer_win1_06415
6415
6433
93
AGTAGTGGAAAATCCTACC
1296
GGTAGGATTTTCCACTACT

NC_045512.2_19mer_win1_06461
6461
6479
94
GTGAAAACTACCGAAGTTG
1297
CAACTTCGGTAGTTTTCAC

NC_045512.2_19mer_win1_06462
6462
6480
95
TGAAAACTACCGAAGTTGT
1298
ACAACTTCGGTAGTTTTCA

NC_045512.2_19mer_win1_06463
6463
6481
96
GAAAACTACCGAAGTTGTA
1299
TACAACTTCGGTAGTTTTC

NC_045512.2_19mer_win1_06464
6464
6482
97
AAAACTACCGAAGTTGTAG
1300
CTACAACTTCGGTAGTTTT

NC_045512.2_19mer_win1_06465
6465
6483
98
AAACTACCGAAGTTGTAGG
1301
CCTACAACTTCGGTAGTTT

NC_045512.2_19mer_win1_07532
7532
7550
99
TGTACAACTATTGTTAATG
1302
CATTAACAATAGTTGTACA

NC_045512.2_19mer_win1_07533
7533
7551
100
GTACAACTATTGTTAATGG
1303
CCATTAACAATAGTTGTAC

NC_045512.2_19mer_win1_09588
9588
9606
101
TTTACTTGTACTTGACATT
1304
AATGTCAAGTACAAGTAAA

NC_045512.2_19mer_win1_10484
10484
10502
102
TCATGTGGTAGTGTTGGTT
1305
AACCAACACTACCACATGA

NC_045512.2_19mer_win1_10485
10485
10503
103
CATGTGGTAGTGTTGGTTT
1306
AAACCAACACTACCACATG

NC_045512.2_19mer_win1_10486
10486
10504
104
ATGTGGTAGTGTTGGTTTT
1307
AAAACCAACACTACCACAT

NC_045512.2_19mer_win1_10487
10487
10505
105
TGTGGTAGTGTTGGTTTTA
1308
TAAAACCAACACTACCACA

NC_045512.2_19mer_win1_10488
10488
10506
106
GTGGTAGTGTTGGTTTTAA
1309
TTAAAACCAACACTACCAC

NC_045512.2_19mer_win1_10489
10489
10507
107
TGGTAGTGTTGGTTTTAAC
1310
GTTAAAACCAACACTACCA

NC_045512.2_19mer_win1_10490
10490
10508
108
GGTAGTGTTGGTTTTAACA
1311
TGTTAAAACCAACACTACC

NC_045512.2_19mer_win1_10491
10491
10509
109
GTAGTGTTGGTTTTAACAT
1312
ATGTTAAAACCAACACTAC

NC_045512.2_19mer_win1_11609
11609
11627
110
GTTTATTGTTTCTTAGGCT
1313
AGCCTAAGAAACAATAAAC

NC_045512.2_19mer_win1_11610
11610
11628
111
TTTATTGTTTCTTAGGCTA
1314
TAGCCTAAGAAACAATAAA

NC_045512.2_19mer_win1_11611
11611
11629
112
TTATTGTTTCTTAGGCTAT
1315
ATAGCCTAAGAAACAATAA

NC_045512.2_19mer_win1_11612
11612
11630
113
TATTGTTTCTTAGGCTATT
1316
AATAGCCTAAGAAACAATA

NC_045512.2_19mer_win1_11834
11834
11852
114
ACTGTACAGTCTAAAATGT
1317
ACATTTTAGACTGTACAGT

NC_045512.2_19mer_win1_11835
11835
11853
115
CTGTACAGTCTAAAATGTC
1318
GACATTTTAGACTGTACAG

NC_045512.2_19mer_win1_12023
12023
12041
116
TCCATGCAGGGTGCTGTAG
1319
CTACAGCACCCTGCATGGA

NC_045512.2_19mer_win1_12024
12024
12042
117
CCATGCAGGGTGCTGTAGA
1320
TCTACAGCACCCTGCATGG

NC_045512.2_19mer_win1_12025
12025
12043
118
CATGCAGGGTGCTGTAGAC
1321
GTCTACAGCACCCTGCATG

NC_045512.2_19mer_win1_12026
12026
12044
119
ATGCAGGGTGCTGTAGACA
1322
TGTCTACAGCACCCTGCAT

NC_045512.2_19mer_win1_12027
12027
12045
120
TGCAGGGTGCTGTAGACAT
1323
ATGTCTACAGCACCCTGCA

NC_045512.2_19mer_win1_12212
12212
12230
121
TCTTTGAATGTGGCTAAAT
1324
ATTTAGCCACATTCAAAGA

NC_045512.2_19mer_win1_12213
12213
12231
122
CTTTGAATGTGGCTAAATC
1325
GATTTAGCCACATTCAAAG

NC_045512.2_19mer_win1_12214
12214
12232
123
TTTGAATGTGGCTAAATCT
1326
AGATTTAGCCACATTCAAA

NC_045512.2_19mer_win1_12215
12215
12233
124
TTGAATGTGGCTAAATCTG
1327
CAGATTTAGCCACATTCAA

NC_045512.2_19mer_win1_12216
12216
12234
125
TGAATGTGGCTAAATCTGA
1328
TCAGATTTAGCCACATTCA

NC_045512.2_19mer_win1_12401
12401
12419
126
AACAACATTATCAACAATG
1329
CATTGTTGATAATGTTGTT

NC_045512.2_19mer_win1_12402
12402
12420
127
ACAACATTATCAACAATGC
1330
GCATTGTTGATAATGTTGT

NC_045512.2_19mer_win1_12839
12839
12857
128
AAATGGGCTAGATTCCCTA
1331
TAGGGAATCTAGCCCATTT

NC_045512.2_19mer_win1_12840
12840
12858
129
AATGGGCTAGATTCCCTAA
1332
TTAGGGAATCTAGCCCATT

NC_045512.2_19mer_win1_12841
12841
12859
130
ATGGGCTAGATTCCCTAAG
1333
CTTAGGGAATCTAGCCCAT

NC_045512.2_19mer_win1_12842
12842
12860
131
TGGGCTAGATTCCCTAAGA
1334
TCTTAGGGAATCTAGCCCA

NC_045512.2_19mer_win1_12843
12843
12861
132
GGGCTAGATTCCCTAAGAG
1335
CTCTTAGGGAATCTAGCCC

NC_045512.2_19mer_win1_12844
12844
12862
133
GGCTAGATTCCCTAAGAGT
1336
ACTCTTAGGGAATCTAGCC

NC_045512.2_19mer_win1_12845
12845
12863
134
GCTAGATTCCCTAAGAGTG
1337
CACTCTTAGGGAATCTAGC

NC_045512.2_19mer_win1_12846
12846
12864
135
CTAGATTCCCTAAGAGTGA
1338
TCACTCTTAGGGAATCTAG

NC_045512.2_19mer_win1_12847
12847
12865
136
TAGATTCCCTAAGAGTGAT
1339
ATCACTCTTAGGGAATCTA

NC_045512.2_19mer_win1_12848
12848
12866
137
AGATTCCCTAAGAGTGATG
1340
CATCACTCTTAGGGAATCT

NC_045512.2_19mer_win1_12849
12849
12867
138
GATTCCCTAAGAGTGATGG
1341
CCATCACTCTTAGGGAATC

NC_045512.2_19mer_win1_12885
12885
12903
139
CAGAACTGGAACCACCTTG
1342
CAAGGTGGTTCCAGTTCTG

NC_045512.2_19mer_win1_12886
12886
12904
140
AGAACTGGAACCACCTTGT
1343
ACAAGGTGGTTCCAGTTCT

NC_045512.2_19mer_win1_12887
12887
12905
141
GAACTGGAACCACCTTGTA
1344
TACAAGGTGGTTCCAGTTC

NC_045512.2_19mer_win1_12888
12888
12906
142
AACTGGAACCACCTTGTAG
1345
CTACAAGGTGGTTCCAGTT

NC_045512.2_19mer_win1_12889
12889
12907
143
ACTGGAACCACCTTGTAGG
1346
CCTACAAGGTGGTTCCAGT

NC_045512.2_19mer_win1_12890
12890
12908
144
CTGGAACCACCTTGTAGGT
1347
ACCTACAAGGTGGTTCCAG

NC_045512.2_19mer_win1_12891
12891
12909
145
TGGAACCACCTTGTAGGTT
1348
AACCTACAAGGTGGTTCCA

NC_045512.2_19mer_win1_12892
12892
12910
146
GGAACCACCTTGTAGGTTT
1349
AAACCTACAAGGTGGTTCC

NC_045512.2_19mer_win1_12893
12893
12911
147
GAACCACCTTGTAGGTTTG
1350
CAAACCTACAAGGTGGTTC

NC_045512.2_19mer_win1_12894
12894
12912
148
AACCACCTTGTAGGTTTGT
1351
ACAAACCTACAAGGTGGTT

NC_045512.2_19mer_win1_12895
12895
12913
149
ACCACCTTGTAGGTTTGTT
1352
AACAAACCTACAAGGTGGT

NC_045512.2_19mer_win1_12896
12896
12914
150
CCACCTTGTAGGTTTGTTA
1353
TAACAAACCTACAAGGTGG

NC_045512.2_19mer_win1_12897
12897
12915
151
CACCTTGTAGGTTTGTTAC
1354
GTAACAAACCTACAAGGTG

NC_045512.2_19mer_win1_12898
12898
12916
152
ACCTTGTAGGTTTGTTACA
1355
TGTAACAAACCTACAAGGT

NC_045512.2_19mer_win1_12899
12899
12917
153
CCTTGTAGGTTTGTTACAG
1356
CTGTAACAAACCTACAAGG

NC_045512.2_19mer_win1_12900
12900
12918
154
CTTGTAGGTTTGTTACAGA
1357
TCTGTAACAAACCTACAAG

NC_045512.2_19mer_win1_12901
12901
12919
155
TTGTAGGTTTGTTACAGAC
1358
GTCTGTAACAAACCTACAA

NC_045512.2_19mer_win1_12902
12902
12920
156
TGTAGGTTTGTTACAGACA
1359
TGTCTGTAACAAACCTACA

NC_045512.2_19mer_win1_12903
12903
12921
157
GTAGGTTTGTTACAGACAC
1360
GTGTCTGTAACAAACCTAC

NC_045512.2_19mer_win1_12904
12904
12922
158
TAGGTTTGTTACAGACACA
1361
TGTGTCTGTAACAAACCTA

NC_045512.2_19mer_win1_12905
12905
12923
159
AGGTTTGTTACAGACACAC
1362
GTGTGTCTGTAACAAACCT

NC_045512.2_19mer_win1_12906
12906
12924
160
GGTTTGTTACAGACACACC
1363
GGTGTGTCTGTAACAAACC

NC_045512.2_19mer_win1_12966
12966
12984
161
TAAACAACCTAAATAGAGG
1364
CCTCTATTTAGGTTGTTTA

NC_045512.2_19mer_win1_12967
12967
12985
162
AAACAACCTAAATAGAGGT
1365
ACCTCTATTTAGGTTGTTT

NC_045512.2_19mer_win1_12968
12968
12986
163
AACAACCTAAATAGAGGTA
1366
TACCTCTATTTAGGTTGTT

NC_045512.2_19mer_win1_12969
12969
12987
164
ACAACCTAAATAGAGGTAT
1367
ATACCTCTATTTAGGTTGT

NC_045512.2_19mer_win1_12970
12970
12988
165
CAACCTAAATAGAGGTATG
1368
CATACCTCTATTTAGGTTG

NC_045512.2_19mer_win1_12971
12971
12989
166
AACCTAAATAGAGGTATGG
1369
CCATACCTCTATTTAGGTT

NC_045512.2_19mer_win1_12972
12972
12990
167
ACCTAAATAGAGGTATGGT
1370
ACCATACCTCTATTTAGGT

NC_045512.2_19mer_win1_13151
13151
13169
168
AAGATGTTGTGTACACACA
1371
TGTGTGTACACAACATCTT

NC_045512.2_19mer_win1_13152
13152
13170
169
AGATGTTGTGTACACACAC
1372
GTGTGTGTACACAACATCT

NC_045512.2_19mer_win1_13153
13153
13171
170
GATGTTGTGTACACACACT
1373
AGTGTGTGTACACAACATC

NC_045512.2_19mer_win1_13154
13154
13172
171
ATGTTGTGTACACACACTG
1374
CAGTGTGTGTACACAACAT

NC_045512.2_19mer_win1_13155
13155
13173
172
TGTTGTGTACACACACTGG
1375
CCAGTGTGTGTACACAACA

NC_045512.2_19mer_win1_13156
13156
13174
173
GTTGTGTACACACACTGGT
1376
ACCAGTGTGTGTACACAAC

NC_045512.2_19mer_win1_13157
13157
13175
174
TTGTGTACACACACTGGTA
1377
TACCAGTGTGTGTACACAA

NC_045512.2_19mer_win1_13158
13158
13176
175
TGTGTACACACACTGGTAC
1378
GTACCAGTGTGTGTACACA

NC_045512.2_19mer_win1_13363
13363
13381
176
AAACACAGTCTGTACCGTC
1379
GACGGTACAGACTGTGTTT

NC_045512.2_19mer_win1_13364
13364
13382
177
AACACAGTCTGTACCGTCT
1380
AGACGGTACAGACTGTGTT

NC_045512.2_19mer_win1_13365
13365
13383
178
ACACAGTCTGTACCGTCTG
1381
CAGACGGTACAGACTGTGT

NC_045512.2_19mer_win1_13366
13366
13384
179
CACAGTCTGTACCGTCTGC
1382
GCAGACGGTACAGACTGTG

NC_045512.2_19mer_win1_13367
13367
13385
180
ACAGTCTGTACCGTCTGCG
1383
CGCAGACGGTACAGACTGT

NC_045512.2_19mer_win1_13368
13368
13386
181
CAGTCTGTACCGTCTGCGG
1384
CCGCAGACGGTACAGACTG

NC_045512.2_19mer_win1_13388
13388
13406
182
ATGTGGAAAGGTTATGGCT
1385
AGCCATAACCTTTCCACAT

NC_045512.2_19mer_win1_13389
13389
13407
183
TGTGGAAAGGTTATGGCTG
1386
CAGCCATAACCTTTCCACA

NC_045512.2_19mer_win1_13390
13390
13408
184
GTGGAAAGGTTATGGCTGT
1387
ACAGCCATAACCTTTCCAC

NC_045512.2_19mer_win1_13391
13391
13409
185
TGGAAAGGTTATGGCTGTA
1388
TACAGCCATAACCTTTCCA

NC_045512.2_19mer_win1_13392
13392
13410
186
GGAAAGGTTATGGCTGTAG
1389
CTACAGCCATAACCTTTCC

NC_045512.2_19mer_win1_13393
13393
13411
187
GAAAGGTTATGGCTGTAGT
1390
ACTACAGCCATAACCTTTC

NC_045512.2_19mer_win1_13394
13394
13412
188
AAAGGTTATGGCTGTAGTT
1391
AACTACAGCCATAACCTTT

NC_045512.2_19mer_win1_13395
13395
13413
189
AAGGTTATGGCTGTAGTTG
1392
CAACTACAGCCATAACCTT

NC_045512.2_19mer_win1_13396
13396
13414
190
AGGTTATGGCTGTAGTTGT
1393
ACAACTACAGCCATAACCT

NC_045512.2_19mer_win1_13397
13397
13415
191
GGTTATGGCTGTAGTTGTG
1394
CACAACTACAGCCATAACC

NC_045512.2_19mer_win1_13398
13398
13416
192
GTTATGGCTGTAGTTGTGA
1395
TCACAACTACAGCCATAAC

NC_045512.2_19mer_win1_13458
13458
13476
193
CGTTTTTAAACGGGTTTGC
1396
GCAAACCCGTTTAAAAACG

NC_045512.2_19mer_win1_13459
13459
13477
194
GTTTTTAAACGGGTTTGCG
1397
CGCAAACCCGTTTAAAAAC

NC_045512.2_19mer_win1_13460
13460
13478
195
TTTTTAAACGGGTTTGCGG
1398
CCGCAAACCCGTTTAAAAA

NC_045512.2_19mer_win1_13461
13461
13479
196
TTTTAAACGGGTTTGCGGT
1399
ACCGCAAACCCGTTTAAAA

NC_045512.2_19mer_win1_13462
13462
13480
197
TTTAAACGGGTTTGCGGTG
1400
CACCGCAAACCCGTTTAAA

NC_045512.2_19mer_win1_13463
13463
13481
198
TTAAACGGGTTTGCGGTGT
1401
ACACCGCAAACCCGTTTAA

NC_045512.2_19mer_win1_13464
13464
13482
199
TAAACGGGTTTGCGGTGTA
1402
TACACCGCAAACCCGTTTA

NC_045512.2_19mer_win1_13465
13465
13483
200
AAACGGGTTTGCGGTGTAA
1403
TTACACCGCAAACCCGTTT

NC_045512.2_19mer_win1_13466
13466
13484
201
AACGGGTTTGCGGTGTAAG
1404
CTTACACCGCAAACCCGTT

NC_045512.2_19mer_win1_13467
13467
13485
202
ACGGGTTTGCGGTGTAAGT
1405
ACTTACACCGCAAACCCGT

NC_045512.2_19mer_win1_13468
13468
13486
203
CGGGTTTGCGGTGTAAGTG
1406
CACTTACACCGCAAACCCG

NC_045512.2_19mer_win1_13469
13469
13487
204
GGGTTTGCGGTGTAAGTGC
1407
GCACTTACACCGCAAACCC

NC_045512.2_19mer_win1_13470
13470
13488
205
GGTTTGCGGTGTAAGTGCA
1408
TGCACTTACACCGCAAACC

NC_045512.2_19mer_win1_13471
13471
13489
206
GTTTGCGGTGTAAGTGCAG
1409
CTGCACTTACACCGCAAAC

NC_045512.2_19mer_win1_13472
13472
13490
207
TTTGCGGTGTAAGTGCAGC
1410
GCTGCACTTACACCGCAAA

NC_045512.2_19mer_win1_13473
13473
13491
208
TTGCGGTGTAAGTGCAGCC
1411
GGCTGCACTTACACCGCAA

NC_045512.2_19mer_win1_13474
13474
13492
209
TGCGGTGTAAGTGCAGCCC
1412
GGGCTGCACTTACACCGCA

NC_045512.2_19mer_win1_13475
13475
13493
210
GCGGTGTAAGTGCAGCCCG
1413
CGGGCTGCACTTACACCGC

NC_045512.2_19mer_win1_13476
13476
13494
211
CGGTGTAAGTGCAGCCCGT
1414
ACGGGCTGCACTTACACCG

NC_045512.2_19mer_win1_13477
13477
13495
212
GGTGTAAGTGCAGCCCGTC
1415
GACGGGCTGCACTTACACC

NC_045512.2_19mer_win1_13478
13478
13496
213
GTGTAAGTGCAGCCCGTCT
1416
AGACGGGCTGCACTTACAC

NC_045512.2_19mer_win1_13479
13479
13497
214
TGTAAGTGCAGCCCGTCTT
1417
AAGACGGGCTGCACTTACA

NC_045512.2_19mer_win1_13480
13480
13498
215
GTAAGTGCAGCCCGTCTTA
1418
TAAGACGGGCTGCACTTAC

NC_045512.2_19mer_win1_13481
13481
13499
216
TAAGTGCAGCCCGTCTTAC
1419
GTAAGACGGGCTGCACTTA

NC_045512.2_19mer_win1_13482
13482
13500
217
AAGTGCAGCCCGTCTTACA
1420
TGTAAGACGGGCTGCACTT

NC_045512.2_19mer_win1_13483
13483
13501
218
AGTGCAGCCCGTCTTACAC
1421
GTGTAAGACGGGCTGCACT

NC_045512.2_19mer_win1_13484
13484
13502
219
GTGCAGCCCGTCTTACACC
1422
GGTGTAAGACGGGCTGCAC

NC_045512.2_19mer_win1_13485
13485
13503
220
TGCAGCCCGTCTTACACCG
1423
CGGTGTAAGACGGGCTGCA

NC_045512.2_19mer_win1_13486
13486
13504
221
GCAGCCCGTCTTACACCGT
1424
ACGGTGTAAGACGGGCTGC

NC_045512.2_19mer_win1_13487
13487
13505
222
CAGCCCGTCTTACACCGTG
1425
CACGGTGTAAGACGGGCTG

NC_045512.2_19mer_win1_13488
13488
13506
223
AGCCCGTCTTACACCGTGC
1426
GCACGGTGTAAGACGGGCT

NC_045512.2_19mer_win1_13489
13489
13507
224
GCCCGTCTTACACCGTGCG
1427
CGCACGGTGTAAGACGGGC

NC_045512.2_19mer_win1_13490
13490
13508
225
CCCGTCTTACACCGTGCGG
1428
CCGCACGGTGTAAGACGGG

NC_045512.2_19mer_win1_13491
13491
13509
226
CCGTCTTACACCGTGCGGC
1429
GCCGCACGGTGTAAGACGG

NC_045512.2_19mer_win1_13492
13492
13510
227
CGTCTTACACCGTGCGGCA
1430
TGCCGCACGGTGTAAGACG

NC_045512.2_19mer_win1_13493
13493
13511
228
GTCTTACACCGTGCGGCAC
1431
GTGCCGCACGGTGTAAGAC

NC_045512.2_19mer_win1_13494
13494
13512
229
TCTTACACCGTGCGGCACA
1432
TGTGCCGCACGGTGTAAGA

NC_045512.2_19mer_win1_13495
13495
13513
230
CTTACACCGTGCGGCACAG
1433
CTGTGCCGCACGGTGTAAG

NC_045512.2_19mer_win1_13496
13496
13514
231
TTACACCGTGCGGCACAGG
1434
CCTGTGCCGCACGGTGTAA

NC_045512.2_19mer_win1_13497
13497
13515
232
TACACCGTGCGGCACAGGC
1435
GCCTGTGCCGCACGGTGTA

NC_045512.2_19mer_win1_13498
13498
13516
233
ACACCGTGCGGCACAGGCA
1436
TGCCTGTGCCGCACGGTGT

NC_045512.2_19mer_win1_13499
13499
13517
234
CACCGTGCGGCACAGGCAC
1437
GTGCCTGTGCCGCACGGTG

NC_045512.2_19mer_win1_13500
13500
13518
235
ACCGTGCGGCACAGGCACT
1438
AGTGCCTGTGCCGCACGGT

NC_045512.2_19mer_win1_13501
13501
13519
236
CCGTGCGGCACAGGCACTA
1439
TAGTGCCTGTGCCGCACGG

NC_045512.2_19mer_win1_13502
13502
13520
237
CGTGCGGCACAGGCACTAG
1440
CTAGTGCCTGTGCCGCACG

NC_045512.2_19mer_win1_13762
13762
13780
238
GGTGACATGGTACCACATA
1441
TATGTGGTACCATGTCACC

NC_045512.2_19mer_win1_13763
13763
13781
239
GTGACATGGTACCACATAT
1442
ATATGTGGTACCATGTCAC

NC_045512.2_19mer_win1_13764
13764
13782
240
TGACATGGTACCACATATA
1443
TATATGTGGTACCATGTCA

NC_045512.2_19mer_win1_13765
13765
13783
241
GACATGGTACCACATATAT
1444
ATATATGTGGTACCATGTC

NC_045512.2_19mer_win1_13766
13766
13784
242
ACATGGTACCACATATATC
1445
GATATATGTGGTACCATGT

NC_045512.2_19mer_win1_13767
13767
13785
243
CATGGTACCACATATATCA
1446
TGATATATGTGGTACCATG

NC_045512.2_19mer_win1_13768
13768
13786
244
ATGGTACCACATATATCAC
1447
GTGATATATGTGGTACCAT

NC_045512.2_19mer_win1_13769
13769
13787
245
TGGTACCACATATATCACG
1448
CGTGATATATGTGGTACCA

NC_045512.2_19mer_win1_13770
13770
13788
246
GGTACCACATATATCACGT
1449
ACGTGATATATGTGGTACC

NC_045512.2_19mer_win1_13771
13771
13789
247
GTACCACATATATCACGTC
1450
GACGTGATATATGTGGTAC

NC_045512.2_19mer_win1_13772
13772
13790
248
TACCACATATATCACGTCA
1451
TGACGTGATATATGTGGTA

NC_045512.2_19mer_win1_14290
14290
14308
249
GACCGTTATTTTAAATATT
1452
AATATTTAAAATAACGGTC

NC_045512.2_19mer_win1_14291
14291
14309
250
ACCGTTATTTTAAATATTG
1453
CAATATTTAAAATAACGGT

NC_045512.2_19mer_win1_14292
14292
14310
251
CCGTTATTTTAAATATTGG
1454
CCAATATTTAAAATAACGG

NC_045512.2_19mer_win1_14293
14293
14311
252
CGTTATTTTAAATATTGGG
1455
CCCAATATTTAAAATAACG

NC_045512.2_19mer_win1_14294
14294
14312
253
GTTATTTTAAATATTGGGA
1456
TCCCAATATTTAAAATAAC

NC_045512.2_19mer_win1_14404
14404
14422
254
CCACCTACAAGTTTTGGAC
1457
GTCCAAAACTTGTAGGTGG

NC_045512.2_19mer_win1_14405
14405
14423
255
CACCTACAAGTTTTGGACC
1458
GGTCCAAAACTTGTAGGTG

NC_045512.2_19mer_win1_14406
14406
14424
256
ACCTACAAGTTTTGGACCA
1459
TGGTCCAAAACTTGTAGGT

NC_045512.2_19mer_win1_14407
14407
14425
257
CCTACAAGTTTTGGACCAC
1460
GTGGTCCAAAACTTGTAGG

NC_045512.2_19mer_win1_14408
14408
14426
258
CTACAAGTTTTGGACCACT
1461
AGTGGTCCAAAACTTGTAG

NC_045512.2_19mer_win1_14409
14409
14427
259
TACAAGTTTTGGACCACTA
1462
TAGTGGTCCAAAACTTGTA

NC_045512.2_19mer_win1_14410
14410
14428
260
ACAAGTTTTGGACCACTAG
1463
CTAGTGGTCCAAAACTTGT

NC_045512.2_19mer_win1_14411
14411
14429
261
CAAGTTTTGGACCACTAGT
1464
ACTAGTGGTCCAAAACTTG

NC_045512.2_19mer_win1_14500
14500
14518
262
GTACATAATCAGGATGTAA
1465
TTACATCCTGATTATGTAC

NC_045512.2_19mer_win1_14501
14501
14519
263
TACATAATCAGGATGTAAA
1466
TTTACATCCTGATTATGTA

NC_045512.2_19mer_win1_14502
14502
14520
264
ACATAATCAGGATGTAAAC
1467
GTTTACATCCTGATTATGT

NC_045512.2_19mer_win1_14503
14503
14521
265
CATAATCAGGATGTAAACT
1468
AGTTTACATCCTGATTATG

NC_045512.2_19mer_win1_14504
14504
14522
266
ATAATCAGGATGTAAACTT
1469
AAGTTTACATCCTGATTAT

NC_045512.2_19mer_win1_14505
14505
14523
267
TAATCAGGATGTAAACTTA
1470
TAAGTTTACATCCTGATTA

NC_045512.2_19mer_win1_14506
14506
14524
268
AATCAGGATGTAAACTTAC
1471
GTAAGTTTACATCCTGATT

NC_045512.2_19mer_win1_14507
14507
14525
269
ATCAGGATGTAAACTTACA
1472
TGTAAGTTTACATCCTGAT

NC_045512.2_19mer_win1_14508
14508
14526
270
TCAGGATGTAAACTTACAT
1473
ATGTAAGTTTACATCCTGA

NC_045512.2_19mer_win1_14509
14509
14527
271
CAGGATGTAAACTTACATA
1474
TATGTAAGTTTACATCCTG

NC_045512.2_19mer_win1_14510
14510
14528
272
AGGATGTAAACTTACATAG
1475
CTATGTAAGTTTACATCCT

NC_045512.2_19mer_win1_14511
14511
14529
273
GGATGTAAACTTACATAGC
1476
GCTATGTAAGTTTACATCC

NC_045512.2_19mer_win1_14512
14512
14530
274
GATGTAAACTTACATAGCT
1477
AGCTATGTAAGTTTACATC

NC_045512.2_19mer_win1_14513
14513
14531
275
ATGTAAACTTACATAGCTC
1478
GAGCTATGTAAGTTTACAT

NC_045512.2_19mer_win1_14623
14623
14641
276
TGCTTTTCAGTAGCTGCAC
1479
GTGCAGCTACTGAAAAGCA

NC_045512.2_19mer_win1_14624
14624
14642
277
GCTTTTCAGTAGCTGCACT
1480
AGTGCAGCTACTGAAAAGC

NC_045512.2_19mer_win1_14650
14650
14668
278
AATGTTGCTTTTCAAACTG
1481
CAGTTTGAAAAGCAACATT

NC_045512.2_19mer_win1_14651
14651
14669
279
ATGTTGCTTTTCAAACTGT
1482
ACAGTTTGAAAAGCAACAT

NC_045512.2_19mer_win1_14652
14652
14670
280
TGTTGCTTTTCAAACTGTC
1483
GACAGTTTGAAAAGCAACA

NC_045512.2_19mer_win1_14653
14653
14671
281
GTTGCTTTTCAAACTGTCA
1484
TGACAGTTTGAAAAGCAAC

NC_045512.2_19mer_win1_14654
14654
14672
282
TTGCTTTTCAAACTGTCAA
1485
TTGACAGTTTGAAAAGCAA

NC_045512.2_19mer_win1_14655
14655
14673
283
TGCTTTTCAAACTGTCAAA
1486
TTTGACAGTTTGAAAAGCA

NC_045512.2_19mer_win1_14656
14656
14674
284
GCTTTTCAAACTGTCAAAC
1487
GTTTGACAGTTTGAAAAGC

NC_045512.2_19mer_win1_14657
14657
14675
285
CTTTTCAAACTGTCAAACC
1488
GGTTTGACAGTTTGAAAAG

NC_045512.2_19mer_win1_14658
14658
14676
286
TTTTCAAACTGTCAAACCC
1489
GGGTTTGACAGTTTGAAAA

NC_045512.2_19mer_win1_14659
14659
14677
287
TTTCAAACTGTCAAACCCG
1490
CGGGTTTGACAGTTTGAAA

NC_045512.2_19mer_win1_14660
14660
14678
288
TTCAAACTGTCAAACCCGG
1491
CCGGGTTTGACAGTTTGAA

NC_045512.2_19mer_win1_14661
14661
14679
289
TCAAACTGTCAAACCCGGT
1492
ACCGGGTTTGACAGTTTGA

NC_045512.2_19mer_win1_14662
14662
14680
290
CAAACTGTCAAACCCGGTA
1493
TACCGGGTTTGACAGTTTG

NC_045512.2_19mer_win1_14663
14663
14681
291
AAACTGTCAAACCCGGTAA
1494
TTACCGGGTTTGACAGTTT

NC_045512.2_19mer_win1_14664
14664
14682
292
AACTGTCAAACCCGGTAAT
1495
ATTACCGGGTTTGACAGTT

NC_045512.2_19mer_win1_14665
14665
14683
293
ACTGTCAAACCCGGTAATT
1496
AATTACCGGGTTTGACAGT

NC_045512.2_19mer_win1_14666
14666
14684
294
CTGTCAAACCCGGTAATTT
1497
AAATTACCGGGTTTGACAG

NC_045512.2_19mer_win1_14667
14667
14685
295
TGTCAAACCCGGTAATTTT
1498
AAAATTACCGGGTTTGACA

NC_045512.2_19mer_win1_14668
14668
14686
296
GTCAAACCCGGTAATTTTA
1499
TAAAATTACCGGGTTTGAC

NC_045512.2_19mer_win1_14669
14669
14687
297
TCAAACCCGGTAATTTTAA
1500
TTAAAATTACCGGGTTTGA

NC_045512.2_19mer_win1_14698
14698
14716
298
TATGACTTTGCTGTGTCTA
1501
TAGACACAGCAAAGTCATA

NC_045512.2_19mer_win1_14699
14699
14717
299
ATGACTTTGCTGTGTCTAA
1502
TTAGACACAGCAAAGTCAT

NC_045512.2_19mer_win1_14722
14722
14740
300
TTCTTTAAGGAAGGAAGTT
1503
AACTTCCTTCCTTAAAGAA

NC_045512.2_19mer_win1_14723
14723
14741
301
TCTTTAAGGAAGGAAGTTC
1504
GAACTTCCTTCCTTAAAGA

NC_045512.2_19mer_win1_14724
14724
14742
302
CTTTAAGGAAGGAAGTTCT
1505
AGAACTTCCTTCCTTAAAG

NC_045512.2_19mer_win1_14725
14725
14743
303
TTTAAGGAAGGAAGTTCTG
1506
CAGAACTTCCTTCCTTAAA

NC_045512.2_19mer_win1_14726
14726
14744
304
TTAAGGAAGGAAGTTCTGT
1507
ACAGAACTTCCTTCCTTAA

NC_045512.2_19mer_win1_14727
14727
14745
305
TAAGGAAGGAAGTTCTGTT
1508
AACAGAACTTCCTTCCTTA

NC_045512.2_19mer_win1_14728
14728
14746
306
AAGGAAGGAAGTTCTGTTG
1509
CAACAGAACTTCCTTCCTT

NC_045512.2_19mer_win1_14729
14729
14747
307
AGGAAGGAAGTTCTGTTGA
1510
TCAACAGAACTTCCTTCCT

NC_045512.2_19mer_win1_14730
14730
14748
308
GGAAGGAAGTTCTGTTGAA
1511
TTCAACAGAACTTCCTTCC

NC_045512.2_19mer_win1_14750
14750
14768
309
TAAAACACTTCTTCTTTGC
1512
GCAAAGAAGAAGTGTTTTA

NC_045512.2_19mer_win1_14751
14751
14769
310
AAAACACTTCTTCTTTGCT
1513
AGCAAAGAAGAAGTGTTTT

NC_045512.2_19mer_win1_14752
14752
14770
311
AAACACTTCTTCTTTGCTC
1514
GAGCAAAGAAGAAGTGTTT

NC_045512.2_19mer_win1_14753
14753
14771
312
AACACTTCTTCTTTGCTCA
1515
TGAGCAAAGAAGAAGTGTT

NC_045512.2_19mer_win1_14754
14754
14772
313
ACACTTCTTCTTTGCTCAG
1516
CTGAGCAAAGAAGAAGTGT

NC_045512.2_19mer_win1_14755
14755
14773
314
CACTTCTTCTTTGCTCAGG
1517
CCTGAGCAAAGAAGAAGTG

NC_045512.2_19mer_win1_14756
14756
14774
315
ACTTCTTCTTTGCTCAGGA
1518
TCCTGAGCAAAGAAGAAGT

NC_045512.2_19mer_win1_14757
14757
14775
316
CTTCTTCTTTGCTCAGGAT
1519
ATCCTGAGCAAAGAAGAAG

NC_045512.2_19mer_win1_14758
14758
14776
317
TTCTTCTTTGCTCAGGATG
1520
CATCCTGAGCAAAGAAGAA

NC_045512.2_19mer_win1_14759
14759
14777
318
TCTTCTTTGCTCAGGATGG
1521
CCATCCTGAGCAAAGAAGA

NC_045512.2_19mer_win1_14821
14821
14839
319
CCAACAATGTGTGATATCA
1522
TGATATCACACATTGTTGG

NC_045512.2_19mer_win1_14822
14822
14840
320
CAACAATGTGTGATATCAG
1523
CTGATATCACACATTGTTG

NC_045512.2_19mer_win1_14823
14823
14841
321
AACAATGTGTGATATCAGA
1524
TCTGATATCACACATTGTT

NC_045512.2_19mer_win1_14824
14824
14842
322
ACAATGTGTGATATCAGAC
1525
GTCTGATATCACACATTGT

NC_045512.2_19mer_win1_14825
14825
14843
323
CAATGTGTGATATCAGACA
1526
TGTCTGATATCACACATTG

NC_045512.2_19mer_win1_14826
14826
14844
324
AATGTGTGATATCAGACAA
1527
TTGTCTGATATCACACATT

NC_045512.2_19mer_win1_14827
14827
14845
325
ATGTGTGATATCAGACAAC
1528
GTTGTCTGATATCACACAT

NC_045512.2_19mer_win1_14828
14828
14846
326
TGTGTGATATCAGACAACT
1529
AGTTGTCTGATATCACACA

NC_045512.2_19mer_win1_14854
14854
14872
327
GTAGTTGAAGTTGTTGATA
1530
TATCAACAACTTCAACTAC

NC_045512.2_19mer_win1_14855
14855
14873
328
TAGTTGAAGTTGTTGATAA
1531
TTATCAACAACTTCAACTA

NC_045512.2_19mer_win1_14875
14875
14893
329
TACTTTGATTGTTACGATG
1532
CATCGTAACAATCAAAGTA

NC_045512.2_19mer_win1_14876
14876
14894
330
ACTTTGATTGTTACGATGG
1533
CCATCGTAACAATCAAAGT

NC_045512.2_19mer_win1_14877
14877
14895
331
CTTTGATTGTTACGATGGT
1534
ACCATCGTAACAATCAAAG

NC_045512.2_19mer_win1_14878
14878
14896
332
TTTGATTGTTACGATGGTG
1535
CACCATCGTAACAATCAAA

NC_045512.2_19mer_win1_14879
14879
14897
333
TTGATTGTTACGATGGTGG
1536
CCACCATCGTAACAATCAA

NC_045512.2_19mer_win1_14880
14880
14898
334
TGATTGTTACGATGGTGGC
1537
GCCACCATCGTAACAATCA

NC_045512.2_19mer_win1_14881
14881
14899
335
GATTGTTACGATGGTGGCT
1538
AGCCACCATCGTAACAATC

NC_045512.2_19mer_win1_14882
14882
14900
336
ATTGTTACGATGGTGGCTG
1539
CAGCCACCATCGTAACAAT

NC_045512.2_19mer_win1_14883
14883
14901
337
TTGTTACGATGGTGGCTGT
1540
ACAGCCACCATCGTAACAA

NC_045512.2_19mer_win1_14884
14884
14902
338
TGTTACGATGGTGGCTGTA
1541
TACAGCCACCATCGTAACA

NC_045512.2_19mer_win1_14885
14885
14903
339
GTTACGATGGTGGCTGTAT
1542
ATACAGCCACCATCGTAAC

NC_045512.2_19mer_win1_14962
14962
14980
340
AAATGGGGTAAGGCTAGAC
1543
GTCTAGCCTTACCCCATTT

NC_045512.2_19mer_win1_14963
14963
14981
341
AATGGGGTAAGGCTAGACT
1544
AGTCTAGCCTTACCCCATT

NC_045512.2_19mer_win1_14964
14964
14982
342
ATGGGGTAAGGCTAGACTT
1545
AAGTCTAGCCTTACCCCAT

NC_045512.2_19mer_win1_14965
14965
14983
343
TGGGGTAAGGCTAGACTTT
1546
AAAGTCTAGCCTTACCCCA

NC_045512.2_19mer_win1_14966
14966
14984
344
GGGGTAAGGCTAGACTTTA
1547
TAAAGTCTAGCCTTACCCC

NC_045512.2_19mer_win1_14967
14967
14985
345
GGGTAAGGCTAGACTTTAT
1548
ATAAAGTCTAGCCTTACCC

NC_045512.2_19mer_win1_14968
14968
14986
346
GGTAAGGCTAGACTTTATT
1549
AATAAAGTCTAGCCTTACC

NC_045512.2_19mer_win1_14969
14969
14987
347
GTAAGGCTAGACTTTATTA
1550
TAATAAAGTCTAGCCTTAC

NC_045512.2_19mer_win1_14970
14970
14988
348
TAAGGCTAGACTTTATTAT
1551
ATAATAAAGTCTAGCCTTA

NC_045512.2_19mer_win1_14971
14971
14989
349
AAGGCTAGACTTTATTATG
1552
CATAATAAAGTCTAGCCTT

NC_045512.2_19mer_win1_14972
14972
14990
350
AGGCTAGACTTTATTATGA
1553
TCATAATAAAGTCTAGCCT

NC_045512.2_19mer_win1_14992
14992
15010
351
TCAATGAGTTATGAGGATC
1554
GATCCTCATAACTCATTGA

NC_045512.2_19mer_win1_14993
14993
15011
352
CAATGAGTTATGAGGATCA
1555
TGATCCTCATAACTCATTG

NC_045512.2_19mer_win1_14994
14994
15012
353
AATGAGTTATGAGGATCAA
1556
TTGATCCTCATAACTCATT

NC_045512.2_19mer_win1_14995
14995
15013
354
ATGAGTTATGAGGATCAAG
1557
CTTGATCCTCATAACTCAT

NC_045512.2_19mer_win1_14996
14996
15014
355
TGAGTTATGAGGATCAAGA
1558
TCTTGATCCTCATAACTCA

NC_045512.2_19mer_win1_14997
14997
15015
356
GAGTTATGAGGATCAAGAT
1559
ATCTTGATCCTCATAACTC

NC_045512.2_19mer_win1_14998
14998
15016
357
AGTTATGAGGATCAAGATG
1560
CATCTTGATCCTCATAACT

NC_045512.2_19mer_win1_14999
14999
15017
358
GTTATGAGGATCAAGATGC
1561
GCATCTTGATCCTCATAAC

NC_045512.2_19mer_win1_15000
15000
15018
359
TTATGAGGATCAAGATGCA
1562
TGCATCTTGATCCTCATAA

NC_045512.2_19mer_win1_15001
15001
15019
360
TATGAGGATCAAGATGCAC
1563
GTGCATCTTGATCCTCATA

NC_045512.2_19mer_win1_15002
15002
15020
361
ATGAGGATCAAGATGCACT
1564
AGTGCATCTTGATCCTCAT

NC_045512.2_19mer_win1_15055
15055
15073
362
ATAACTCAAATGAATCTTA
1565
TAAGATTCATTTGAGTTAT

NC_045512.2_19mer_win1_15056
15056
15074
363
TAACTCAAATGAATCTTAA
1566
TTAAGATTCATTTGAGTTA

NC_045512.2_19mer_win1_15057
15057
15075
364
AACTCAAATGAATCTTAAG
1567
CTTAAGATTCATTTGAGTT

NC_045512.2_19mer_win1_15058
15058
15076
365
ACTCAAATGAATCTTAAGT
1568
ACTTAAGATTCATTTGAGT

NC_045512.2_19mer_win1_15059
15059
15077
366
CTCAAATGAATCTTAAGTA
1569
TACTTAAGATTCATTTGAG

NC_045512.2_19mer_win1_15060
15060
15078
367
TCAAATGAATCTTAAGTAT
1570
ATACTTAAGATTCATTTGA

NC_045512.2_19mer_win1_15061
15061
15079
368
CAAATGAATCTTAAGTATG
1571
CATACTTAAGATTCATTTG

NC_045512.2_19mer_win1_15062
15062
15080
369
AAATGAATCTTAAGTATGC
1572
GCATACTTAAGATTCATTT

NC_045512.2_19mer_win1_15063
15063
15081
370
AATGAATCTTAAGTATGCC
1573
GGCATACTTAAGATTCATT

NC_045512.2_19mer_win1_15064
15064
15082
371
ATGAATCTTAAGTATGCCA
1574
TGGCATACTTAAGATTCAT

NC_045512.2_19mer_win1_15065
15065
15083
372
TGAATCTTAAGTATGCCAT
1575
ATGGCATACTTAAGATTCA

NC_045512.2_19mer_win1_15066
15066
15084
373
GAATCTTAAGTATGCCATT
1576
AATGGCATACTTAAGATTC

NC_045512.2_19mer_win1_15067
15067
15085
374
AATCTTAAGTATGCCATTA
1577
TAATGGCATACTTAAGATT

NC_045512.2_19mer_win1_15068
15068
15086
375
ATCTTAAGTATGCCATTAG
1578
CTAATGGCATACTTAAGAT

NC_045512.2_19mer_win1_15069
15069
15087
376
TCTTAAGTATGCCATTAGT
1579
ACTAATGGCATACTTAAGA

NC_045512.2_19mer_win1_15070
15070
15088
377
CTTAAGTATGCCATTAGTG
1580
CACTAATGGCATACTTAAG

NC_045512.2_19mer_win1_15071
15071
15089
378
TTAAGTATGCCATTAGTGC
1581
GCACTAATGGCATACTTAA

NC_045512.2_19mer_win1_15072
15072
15090
379
TAAGTATGCCATTAGTGCA
1582
TGCACTAATGGCATACTTA

NC_045512.2_19mer_win1_15073
15073
15091
380
AAGTATGCCATTAGTGCAA
1583
TTGCACTAATGGCATACTT

NC_045512.2_19mer_win1_15074
15074
15092
381
AGTATGCCATTAGTGCAAA
1584
TTTGCACTAATGGCATACT

NC_045512.2_19mer_win1_15075
15075
15093
382
GTATGCCATTAGTGCAAAG
1585
CTTTGCACTAATGGCATAC

NC_045512.2_19mer_win1_15076
15076
15094
383
TATGCCATTAGTGCAAAGA
1586
TCTTTGCACTAATGGCATA

NC_045512.2_19mer_win1_15077
15077
15095
384
ATGCCATTAGTGCAAAGAA
1587
TTCTTTGCACTAATGGCAT

NC_045512.2_19mer_win1_15078
15078
15096
385
TGCCATTAGTGCAAAGAAT
1588
ATTCTTTGCACTAATGGCA

NC_045512.2_19mer_win1_15079
15079
15097
386
GCCATTAGTGCAAAGAATA
1589
TATTCTTTGCACTAATGGC

NC_045512.2_19mer_win1_15080
15080
15098
387
CCATTAGTGCAAAGAATAG
1590
CTATTCTTTGCACTAATGG

NC_045512.2_19mer_win1_15081
15081
15099
388
CATTAGTGCAAAGAATAGA
1591
TCTATTCTTTGCACTAATG

NC_045512.2_19mer_win1_15082
15082
15100
389
ATTAGTGCAAAGAATAGAG
1592
CTCTATTCTTTGCACTAAT

NC_045512.2_19mer_win1_15083
15083
15101
390
TTAGTGCAAAGAATAGAGC
1593
GCTCTATTCTTTGCACTAA

NC_045512.2_19mer_win1_15084
15084
15102
391
TAGTGCAAAGAATAGAGCT
1594
AGCTCTATTCTTTGCACTA

NC_045512.2_19mer_win1_15085
15085
15103
392
AGTGCAAAGAATAGAGCTC
1595
GAGCTCTATTCTTTGCACT

NC_045512.2_19mer_win1_15086
15086
15104
393
GTGCAAAGAATAGAGCTCG
1596
CGAGCTCTATTCTTTGCAC

NC_045512.2_19mer_win1_15087
15087
15105
394
TGCAAAGAATAGAGCTCGC
1597
GCGAGCTCTATTCTTTGCA

NC_045512.2_19mer_win1_15088
15088
15106
395
GCAAAGAATAGAGCTCGCA
1598
TGCGAGCTCTATTCTTTGC

NC_045512.2_19mer_win1_15089
15089
15107
396
CAAAGAATAGAGCTCGCAC
1599
GTGCGAGCTCTATTCTTTG

NC_045512.2_19mer_win1_15090
15090
15108
397
AAAGAATAGAGCTCGCACC
1600
GGTGCGAGCTCTATTCTTT

NC_045512.2_19mer_win1_15091
15091
15109
398
AAGAATAGAGCTCGCACCG
1601
CGGTGCGAGCTCTATTCTT

NC_045512.2_19mer_win1_15092
15092
15110
399
AGAATAGAGCTCGCACCGT
1602
ACGGTGCGAGCTCTATTCT

NC_045512.2_19mer_win1_15093
15093
15111
400
GAATAGAGCTCGCACCGTA
1603
TACGGTGCGAGCTCTATTC

NC_045512.2_19mer_win1_15094
15094
15112
401
AATAGAGCTCGCACCGTAG
1604
CTACGGTGCGAGCTCTATT

NC_045512.2_19mer_win1_15095
15095
15113
402
ATAGAGCTCGCACCGTAGC
1605
GCTACGGTGCGAGCTCTAT

NC_045512.2_19mer_win1_15096
15096
15114
403
TAGAGCTCGCACCGTAGCT
1606
AGCTACGGTGCGAGCTCTA

NC_045512.2_19mer_win1_15097
15097
15115
404
AGAGCTCGCACCGTAGCTG
1607
CAGCTACGGTGCGAGCTCT

NC_045512.2_19mer_win1_15098
15098
15116
405
GAGCTCGCACCGTAGCTGG
1608
CCAGCTACGGTGCGAGCTC

NC_045512.2_19mer_win1_15099
15099
15117
406
AGCTCGCACCGTAGCTGGT
1609
ACCAGCTACGGTGCGAGCT

NC_045512.2_19mer_win1_15100
15100
15118
407
GCTCGCACCGTAGCTGGTG
1610
CACCAGCTACGGTGCGAGC

NC_045512.2_19mer_win1_15101
15101
15119
408
CTCGCACCGTAGCTGGTGT
1611
ACACCAGCTACGGTGCGAG

NC_045512.2_19mer_win1_15102
15102
15120
409
TCGCACCGTAGCTGGTGTC
1612
GACACCAGCTACGGTGCGA

NC_045512.2_19mer_win1_15103
15103
15121
410
CGCACCGTAGCTGGTGTCT
1613
AGACACCAGCTACGGTGCG

NC_045512.2_19mer_win1_15104
15104
15122
411
GCACCGTAGCTGGTGTCTC
1614
GAGACACCAGCTACGGTGC

NC_045512.2_19mer_win1_15105
15105
15123
412
CACCGTAGCTGGTGTCTCT
1615
AGAGACACCAGCTACGGTG

NC_045512.2_19mer_win1_15106
15106
15124
413
ACCGTAGCTGGTGTCTCTA
1616
TAGAGACACCAGCTACGGT

NC_045512.2_19mer_win1_15107
15107
15125
414
CCGTAGCTGGTGTCTCTAT
1617
ATAGAGACACCAGCTACGG

NC_045512.2_19mer_win1_15108
15108
15126
415
CGTAGCTGGTGTCTCTATC
1618
GATAGAGACACCAGCTACG

NC_045512.2_19mer_win1_15109
15109
15127
416
GTAGCTGGTGTCTCTATCT
1619
AGATAGAGACACCAGCTAC

NC_045512.2_19mer_win1_15110
15110
15128
417
TAGCTGGTGTCTCTATCTG
1620
CAGATAGAGACACCAGCTA

NC_045512.2_19mer_win1_15111
15111
15129
418
AGCTGGTGTCTCTATCTGT
1621
ACAGATAGAGACACCAGCT

NC_045512.2_19mer_win1_15112
15112
15130
419
GCTGGTGTCTCTATCTGTA
1622
TACAGATAGAGACACCAGC

NC_045512.2_19mer_win1_15113
15113
15131
420
CTGGTGTCTCTATCTGTAG
1623
CTACAGATAGAGACACCAG

NC_045512.2_19mer_win1_15114
15114
15132
421
TGGTGTCTCTATCTGTAGT
1624
ACTACAGATAGAGACACCA

NC_045512.2_19mer_win1_15115
15115
15133
422
GGTGTCTCTATCTGTAGTA
1625
TACTACAGATAGAGACACC

NC_045512.2_19mer_win1_15116
15116
15134
423
GTGTCTCTATCTGTAGTAC
1626
GTACTACAGATAGAGACAC

NC_045512.2_19mer_win1_15117
15117
15135
424
TGTCTCTATCTGTAGTACT
1627
AGTACTACAGATAGAGACA

NC_045512.2_19mer_win1_15118
15118
15136
425
GTCTCTATCTGTAGTACTA
1628
TAGTACTACAGATAGAGAC

NC_045512.2_19mer_win1_15119
15119
15137
426
TCTCTATCTGTAGTACTAT
1629
ATAGTACTACAGATAGAGA

NC_045512.2_19mer_win1_15120
15120
15138
427
CTCTATCTGTAGTACTATG
1630
CATAGTACTACAGATAGAG

NC_045512.2_19mer_win1_15121
15121
15139
428
TCTATCTGTAGTACTATGA
1631
TCATAGTACTACAGATAGA

NC_045512.2_19mer_win1_15122
15122
15140
429
CTATCTGTAGTACTATGAC
1632
GTCATAGTACTACAGATAG

NC_045512.2_19mer_win1_15172
15172
15190
430
TCAATAGCCGCCACTAGAG
1633
CTCTAGTGGCGGCTATTGA

NC_045512.2_19mer_win1_15173
15173
15191
431
CAATAGCCGCCACTAGAGG
1634
CCTCTAGTGGCGGCTATTG

NC_045512.2_19mer_win1_15174
15174
15192
432
AATAGCCGCCACTAGAGGA
1635
TCCTCTAGTGGCGGCTATT

NC_045512.2_19mer_win1_15175
15175
15193
433
ATAGCCGCCACTAGAGGAG
1636
CTCCTCTAGTGGCGGCTAT

NC_045512.2_19mer_win1_15176
15176
15194
434
TAGCCGCCACTAGAGGAGC
1637
GCTCCTCTAGTGGCGGCTA

NC_045512.2_19mer_win1_15177
15177
15195
435
AGCCGCCACTAGAGGAGCT
1638
AGCTCCTCTAGTGGCGGCT

NC_045512.2_19mer_win1_15178
15178
15196
436
GCCGCCACTAGAGGAGCTA
1639
TAGCTCCTCTAGTGGCGGC

NC_045512.2_19mer_win1_15179
15179
15197
437
CCGCCACTAGAGGAGCTAC
1640
GTAGCTCCTCTAGTGGCGG

NC_045512.2_19mer_win1_15180
15180
15198
438
CGCCACTAGAGGAGCTACT
1641
AGTAGCTCCTCTAGTGGCG

NC_045512.2_19mer_win1_15181
15181
15199
439
GCCACTAGAGGAGCTACTG
1642
CAGTAGCTCCTCTAGTGGC

NC_045512.2_19mer_win1_15182
15182
15200
440
CCACTAGAGGAGCTACTGT
1643
ACAGTAGCTCCTCTAGTGG

NC_045512.2_19mer_win1_15310
15310
15328
441
AGAGCCATGCCTAACATGC
1644
GCATGTTAGGCATGGCTCT

NC_045512.2_19mer_win1_15311
15311
15329
442
GAGCCATGCCTAACATGCT
1645
AGCATGTTAGGCATGGCTC

NC_045512.2_19mer_win1_15312
15312
15330
443
AGCCATGCCTAACATGCTT
1646
AAGCATGTTAGGCATGGCT

NC_045512.2_19mer_win1_15313
15313
15331
444
GCCATGCCTAACATGCTTA
1647
TAAGCATGTTAGGCATGGC

NC_045512.2_19mer_win1_15314
15314
15332
445
CCATGCCTAACATGCTTAG
1648
CTAAGCATGTTAGGCATGG

NC_045512.2_19mer_win1_15346
15346
15364
446
CTTGTTCTTGCTCGCAAAC
1649
GTTTGCGAGCAAGAACAAG

NC_045512.2_19mer_win1_15347
15347
15365
447
TTGTTCTTGCTCGCAAACA
1650
TGTTTGCGAGCAAGAACAA

NC_045512.2_19mer_win1_15348
15348
15366
448
TGTTCTTGCTCGCAAACAT
1651
ATGTTTGCGAGCAAGAACA

NC_045512.2_19mer_win1_15349
15349
15367
449
GTTCTTGCTCGCAAACATA
1652
TATGTTTGCGAGCAAGAAC

NC_045512.2_19mer_win1_15496
15496
15514
450
ACAACTGCTTATGCTAATA
1653
TATTAGCATAAGCAGTTGT

NC_045512.2_19mer_win1_15497
15497
15515
451
CAACTGCTTATGCTAATAG
1654
CTATTAGCATAAGCAGTTG

NC_045512.2_19mer_win1_15498
15498
15516
452
AACTGCTTATGCTAATAGT
1655
ACTATTAGCATAAGCAGTT

NC_045512.2_19mer_win1_15499
15499
15517
453
ACTGCTTATGCTAATAGTG
1656
CACTATTAGCATAAGCAGT

NC_045512.2_19mer_win1_15500
15500
15518
454
CTGCTTATGCTAATAGTGT
1657
ACACTATTAGCATAAGCAG

NC_045512.2_19mer_win1_15622
15622
15640
455
TATGAGTGTCTCTATAGAA
1658
TTCTATAGAGACACTCATA

NC_045512.2_19mer_win1_15623
15623
15641
456
ATGAGTGTCTCTATAGAAA
1659
TTTCTATAGAGACACTCAT

NC_045512.2_19mer_win1_15624
15624
15642
457
TGAGTGTCTCTATAGAAAT
1660
ATTTCTATAGAGACACTCA

NC_045512.2_19mer_win1_15625
15625
15643
458
GAGTGTCTCTATAGAAATA
1661
TATTTCTATAGAGACACTC

NC_045512.2_19mer_win1_15626
15626
15644
459
AGTGTCTCTATAGAAATAG
1662
CTATTTCTATAGAGACACT

NC_045512.2_19mer_win1_15838
15838
15856
460
TGGACTGAGACTGACCTTA
1663
TAAGGTCAGTCTCAGTCCA

NC_045512.2_19mer_win1_15839
15839
15857
461
GGACTGAGACTGACCTTAC
1664
GTAAGGTCAGTCTCAGTCC

NC_045512.2_19mer_win1_15840
15840
15858
462
GACTGAGACTGACCTTACT
1665
AGTAAGGTCAGTCTCAGTC

NC_045512.2_19mer_win1_15841
15841
15859
463
ACTGAGACTGACCTTACTA
1666
TAGTAAGGTCAGTCTCAGT

NC_045512.2_19mer_win1_15842
15842
15860
464
CTGAGACTGACCTTACTAA
1667
TTAGTAAGGTCAGTCTCAG

NC_045512.2_19mer_win1_15843
15843
15861
465
TGAGACTGACCTTACTAAA
1668
TTTAGTAAGGTCAGTCTCA

NC_045512.2_19mer_win1_15844
15844
15862
466
GAGACTGACCTTACTAAAG
1669
CTTTAGTAAGGTCAGTCTC

NC_045512.2_19mer_win1_15845
15845
15863
467
AGACTGACCTTACTAAAGG
1670
CCTTTAGTAAGGTCAGTCT

NC_045512.2_19mer_win1_15846
15846
15864
468
GACTGACCTTACTAAAGGA
1671
TCCTTTAGTAAGGTCAGTC

NC_045512.2_19mer_win1_15847
15847
15865
469
ACTGACCTTACTAAAGGAC
1672
GTCCTTTAGTAAGGTCAGT

NC_045512.2_19mer_win1_15848
15848
15866
470
CTGACCTTACTAAAGGACC
1673
GGTCCTTTAGTAAGGTCAG

NC_045512.2_19mer_win1_15849
15849
15867
471
TGACCTTACTAAAGGACCT
1674
AGGTCCTTTAGTAAGGTCA

NC_045512.2_19mer_win1_15850
15850
15868
472
GACCTTACTAAAGGACCTC
1675
GAGGTCCTTTAGTAAGGTC

NC_045512.2_19mer_win1_15851
15851
15869
473
ACCTTACTAAAGGACCTCA
1676
TGAGGTCCTTTAGTAAGGT

NC_045512.2_19mer_win1_15886
15886
15904
474
CATACAATGCTAGTTAAAC
1677
GTTTAACTAGCATTGTATG

NC_045512.2_19mer_win1_15887
15887
15905
475
ATACAATGCTAGTTAAACA
1678
TGTTTAACTAGCATTGTAT

NC_045512.2_19mer_win1_15985
15985
16003
476
AAAACAGATGGTACACTTA
1679
TAAGTGTACCATCTGTTTT

NC_045512.2_19mer_win1_15986
15986
16004
477
AAACAGATGGTACACTTAT
1680
ATAAGTGTACCATCTGTTT

NC_045512.2_19mer_win1_15987
15987
16005
478
AACAGATGGTACACTTATG
1681
CATAAGTGTACCATCTGTT

NC_045512.2_19mer_win1_15988
15988
16006
479
ACAGATGGTACACTTATGA
1682
TCATAAGTGTACCATCTGT

NC_045512.2_19mer_win1_15989
15989
16007
480
CAGATGGTACACTTATGAT
1683
ATCATAAGTGTACCATCTG

NC_045512.2_19mer_win1_15990
15990
16008
481
AGATGGTACACTTATGATT
1684
AATCATAAGTGTACCATCT

NC_045512.2_19mer_win1_15991
15991
16009
482
GATGGTACACTTATGATTG
1685
CAATCATAAGTGTACCATC

NC_045512.2_19mer_win1_15992
15992
16010
483
ATGGTACACTTATGATTGA
1686
TCAATCATAAGTGTACCAT

NC_045512.2_19mer_win1_16057
16057
16075
484
CCTAATCAGGAGTATGCTG
1687
CAGCATACTCCTGATTAGG

NC_045512.2_19mer_win1_16058
16058
16076
485
CTAATCAGGAGTATGCTGA
1688
TCAGCATACTCCTGATTAG

NC_045512.2_19mer_win1_16059
16059
16077
486
TAATCAGGAGTATGCTGAT
1689
ATCAGCATACTCCTGATTA

NC_045512.2_19mer_win1_16060
16060
16078
487
AATCAGGAGTATGCTGATG
1690
CATCAGCATACTCCTGATT

NC_045512.2_19mer_win1_16061
16061
16079
488
ATCAGGAGTATGCTGATGT
1691
ACATCAGCATACTCCTGAT

NC_045512.2_19mer_win1_16186
16186
16204
489
TGGGAACCTGAGTTTTATG
1692
CATAAAACTCAGGTTCCCA

NC_045512.2_19mer_win1_16187
16187
16205
490
GGGAACCTGAGTTTTATGA
1693
TCATAAAACTCAGGTTCCC

NC_045512.2_19mer_win1_16430
16430
16448
491
TAGGAGGTATGAGCTATTA
1694
TAATAGCTCATACCTCCTA

NC_045512.2_19mer_win1_16822
16822
16840
492
GGAGAGTACACCTTTGAAA
1695
TTTCAAAGGTGTACTCTCC

NC_045512.2_19mer_win1_16823
16823
16841
493
GAGAGTACACCTTTGAAAA
1696
TTTTCAAAGGTGTACTCTC

NC_045512.2_19mer_win1_16824
16824
16842
494
AGAGTACACCTTTGAAAAA
1697
TTTTTCAAAGGTGTACTCT

NC_045512.2_19mer_win1_16825
16825
16843
495
GAGTACACCTTTGAAAAAG
1698
CTTTTTCAAAGGTGTACTC

NC_045512.2_19mer_win1_16826
16826
16844
496
AGTACACCTTTGAAAAAGG
1699
CCTTTTTCAAAGGTGTACT

NC_045512.2_19mer_win1_16827
16827
16845
497
GTACACCTTTGAAAAAGGT
1700
ACCTTTTTCAAAGGTGTAC

NC_045512.2_19mer_win1_16828
16828
16846
498
TACACCTTTGAAAAAGGTG
1701
CACCTTTTTCAAAGGTGTA

NC_045512.2_19mer_win1_16829
16829
16847
499
ACACCTTTGAAAAAGGTGA
1702
TCACCTTTTTCAAAGGTGT

NC_045512.2_19mer_win1_16830
16830
16848
500
CACCTTTGAAAAAGGTGAC
1703
GTCACCTTTTTCAAAGGTG

NC_045512.2_19mer_win1_16831
16831
16849
501
ACCTTTGAAAAAGGTGACT
1704
AGTCACCTTTTTCAAAGGT

NC_045512.2_19mer_win1_16832
16832
16850
502
CCTTTGAAAAAGGTGACTA
1705
TAGTCACCTTTTTCAAAGG

NC_045512.2_19mer_win1_16833
16833
16851
503
CTTTGAAAAAGGTGACTAT
1706
ATAGTCACCTTTTTCAAAG

NC_045512.2_19mer_win1_16834
16834
16852
504
TTTGAAAAAGGTGACTATG
1707
CATAGTCACCTTTTTCAAA

NC_045512.2_19mer_win1_16835
16835
16853
505
TTGAAAAAGGTGACTATGG
1708
CCATAGTCACCTTTTTCAA

NC_045512.2_19mer_win1_16836
16836
16854
506
TGAAAAAGGTGACTATGGT
1709
ACCATAGTCACCTTTTTCA

NC_045512.2_19mer_win1_16837
16837
16855
507
GAAAAAGGTGACTATGGTG
1710
CACCATAGTCACCTTTTTC

NC_045512.2_19mer_win1_16838
16838
16856
508
AAAAAGGTGACTATGGTGA
1711
TCACCATAGTCACCTTTTT

NC_045512.2_19mer_win1_16839
16839
16857
509
AAAAGGTGACTATGGTGAT
1712
ATCACCATAGTCACCTTTT

NC_045512.2_19mer_win1_16840
16840
16858
510
AAAGGTGACTATGGTGATG
1713
CATCACCATAGTCACCTTT

NC_045512.2_19mer_win1_16841
16841
16859
511
AAGGTGACTATGGTGATGC
1714
GCATCACCATAGTCACCTT

NC_045512.2_19mer_win1_16842
16842
16860
512
AGGTGACTATGGTGATGCT
1715
AGCATCACCATAGTCACCT

NC_045512.2_19mer_win1_16843
16843
16861
513
GGTGACTATGGTGATGCTG
1716
CAGCATCACCATAGTCACC

NC_045512.2_19mer_win1_16844
16844
16862
514
GTGACTATGGTGATGCTGT
1717
ACAGCATCACCATAGTCAC

NC_045512.2_19mer_win1_16845
16845
16863
515
TGACTATGGTGATGCTGTT
1718
AACAGCATCACCATAGTCA

NC_045512.2_19mer_win1_16846
16846
16864
516
GACTATGGTGATGCTGTTG
1719
CAACAGCATCACCATAGTC

NC_045512.2_19mer_win1_16847
16847
16865
517
ACTATGGTGATGCTGTTGT
1720
ACAACAGCATCACCATAGT

NC_045512.2_19mer_win1_16954
16954
16972
518
CTAGTGCCACAAGAGCACT
1721
AGTGCTCTTGTGGCACTAG

NC_045512.2_19mer_win1_16955
16955
16973
519
TAGTGCCACAAGAGCACTA
1722
TAGTGCTCTTGTGGCACTA

NC_045512.2_19mer_win1_16956
16956
16974
520
AGTGCCACAAGAGCACTAT
1723
ATAGTGCTCTTGTGGCACT

NC_045512.2_19mer_win1_16957
16957
16975
521
GTGCCACAAGAGCACTATG
1724
CATAGTGCTCTTGTGGCAC

NC_045512.2_19mer_win1_16958
16958
16976
522
TGCCACAAGAGCACTATGT
1725
ACATAGTGCTCTTGTGGCA

NC_045512.2_19mer_win1_17008
17008
17026
523
ATCTCAGATGAGTTTTCTA
1726
TAGAAAACTCATCTGAGAT

NC_045512.2_19mer_win1_17009
17009
17027
524
TCTCAGATGAGTTTTCTAG
1727
CTAGAAAACTCATCTGAGA

NC_045512.2_19mer_win1_17010
17010
17028
525
CTCAGATGAGTTTTCTAGC
1728
GCTAGAAAACTCATCTGAG

NC_045512.2_19mer_win1_17011
17011
17029
526
TCAGATGAGTTTTCTAGCA
1729
TGCTAGAAAACTCATCTGA

NC_045512.2_19mer_win1_17012
17012
17030
527
CAGATGAGTTTTCTAGCAA
1730
TTGCTAGAAAACTCATCTG

NC_045512.2_19mer_win1_17013
17013
17031
528
AGATGAGTTTTCTAGCAAT
1731
ATTGCTAGAAAACTCATCT

NC_045512.2_19mer_win1_17014
17014
17032
529
GATGAGTTTTCTAGCAATG
1732
CATTGCTAGAAAACTCATC

NC_045512.2_19mer_win1_17015
17015
17033
530
ATGAGTTTTCTAGCAATGT
1733
ACATTGCTAGAAAACTCAT

NC_045512.2_19mer_win1_17016
17016
17034
531
TGAGTTTTCTAGCAATGTT
1734
AACATTGCTAGAAAACTCA

NC_045512.2_19mer_win1_17017
17017
17035
532
GAGTTTTCTAGCAATGTTG
1735
CAACATTGCTAGAAAACTC

NC_045512.2_19mer_win1_17018
17018
17036
533
AGTTTTCTAGCAATGTTGC
1736
GCAACATTGCTAGAAAACT

NC_045512.2_19mer_win1_17019
17019
17037
534
GTTTTCTAGCAATGTTGCA
1737
TGCAACATTGCTAGAAAAC

NC_045512.2_19mer_win1_17020
17020
17038
535
TTTTCTAGCAATGTTGCAA
1738
TTGCAACATTGCTAGAAAA

NC_045512.2_19mer_win1_17021
17021
17039
536
TTTCTAGCAATGTTGCAAA
1739
TTTGCAACATTGCTAGAAA

NC_045512.2_19mer_win1_17022
17022
17040
537
TTCTAGCAATGTTGCAAAT
1740
ATTTGCAACATTGCTAGAA

NC_045512.2_19mer_win1_17023
17023
17041
538
TCTAGCAATGTTGCAAATT
1741
AATTTGCAACATTGCTAGA

NC_045512.2_19mer_win1_17024
17024
17042
539
CTAGCAATGTTGCAAATTA
1742
TAATTTGCAACATTGCTAG

NC_045512.2_19mer_win1_17080
17080
17098
540
GGACCACCTGGTACTGGTA
1743
TACCAGTACCAGGTGGTCC

NC_045512.2_19mer_win1_17081
17081
17099
541
GACCACCTGGTACTGGTAA
1744
TTACCAGTACCAGGTGGTC

NC_045512.2_19mer_win1_17082
17082
17100
542
ACCACCTGGTACTGGTAAG
1745
CTTACCAGTACCAGGTGGT

NC_045512.2_19mer_win1_17083
17083
17101
543
CCACCTGGTACTGGTAAGA
1746
TCTTACCAGTACCAGGTGG

NC_045512.2_19mer_win1_17084
17084
17102
544
CACCTGGTACTGGTAAGAG
1747
CTCTTACCAGTACCAGGTG

NC_045512.2_19mer_win1_17085
17085
17103
545
ACCTGGTACTGGTAAGAGT
1748
ACTCTTACCAGTACCAGGT

NC_045512.2_19mer_win1_17086
17086
17104
546
CCTGGTACTGGTAAGAGTC
1749
GACTCTTACCAGTACCAGG

NC_045512.2_19mer_win1_17087
17087
17105
547
CTGGTACTGGTAAGAGTCA
1750
TGACTCTTACCAGTACCAG

NC_045512.2_19mer_win1_17088
17088
17106
548
TGGTACTGGTAAGAGTCAT
1751
ATGACTCTTACCAGTACCA

NC_045512.2_19mer_win1_17089
17089
17107
549
GGTACTGGTAAGAGTCATT
1752
AATGACTCTTACCAGTACC

NC_045512.2_19mer_win1_17090
17090
17108
550
GTACTGGTAAGAGTCATTT
1753
AAATGACTCTTACCAGTAC

NC_045512.2_19mer_win1_17091
17091
17109
551
TACTGGTAAGAGTCATTTT
1754
AAAATGACTCTTACCAGTA

NC_045512.2_19mer_win1_17092
17092
17110
552
ACTGGTAAGAGTCATTTTG
1755
CAAAATGACTCTTACCAGT

NC_045512.2_19mer_win1_17093
17093
17111
553
CTGGTAAGAGTCATTTTGC
1756
GCAAAATGACTCTTACCAG

NC_045512.2_19mer_win1_17137
17137
17155
554
TCTGCTCGCATAGTGTATA
1757
TATACACTATGCGAGCAGA

NC_045512.2_19mer_win1_17138
17138
17156
555
CTGCTCGCATAGTGTATAC
1758
GTATACACTATGCGAGCAG

NC_045512.2_19mer_win1_17269
17269
17287
556
AAATTCAAAGTGAATTCAA
1759
TTGAATTCACTTTGAATTT

NC_045512.2_19mer_win1_17270
17270
17288
557
AATTCAAAGTGAATTCAAC
1760
GTTGAATTCACTTTGAATT

NC_045512.2_19mer_win1_17271
17271
17289
558
ATTCAAAGTGAATTCAACA
1761
TGTTGAATTCACTTTGAAT

NC_045512.2_19mer_win1_17530
17530
17548
559
ATAGGTCCAGACATGTTCC
1762
GGAACATGTCTGGACCTAT

NC_045512.2_19mer_win1_17531
17531
17549
560
TAGGTCCAGACATGTTCCT
1763
AGGAACATGTCTGGACCTA

NC_045512.2_19mer_win1_17563
17563
17581
561
CGTTGTCCTGCTGAAATTG
1764
CAATTTCAGCAGGACAACG

NC_045512.2_19mer_win1_17564
17564
17582
562
GTTGTCCTGCTGAAATTGT
1765
ACAATTTCAGCAGGACAAC

NC_045512.2_19mer_win1_17680
17680
17698
563
CATGATGTTTCATCTGCAA
1766
TTGCAGATGAAACATCATG

NC_045512.2_19mer_win1_17681
17681
17699
564
ATGATGTTTCATCTGCAAT
1767
ATTGCAGATGAAACATCAT

NC_045512.2_19mer_win1_17746
17746
17764
565
CCTGCTTGGAGAAAAGCTG
1768
CAGCTTTTCTCCAAGCAGG

NC_045512.2_19mer_win1_17747
17747
17765
566
CTGCTTGGAGAAAAGCTGT
1769
ACAGCTTTTCTCCAAGCAG

NC_045512.2_19mer_win1_17857
17857
17875
567
TATGACTATGTCATATTCA
1770
TGAATATGACATAGTCATA

NC_045512.2_19mer_win1_17858
17858
17876
568
ATGACTATGTCATATTCAC
1771
GTGAATATGACATAGTCAT

NC_045512.2_19mer_win1_17956
17956
17974
569
TGCATAATGTCTGATAGAG
1772
CTCTATCAGACATTATGCA

NC_045512.2_19mer_win1_17957
17957
17975
570
GCATAATGTCTGATAGAGA
1773
TCTCTATCAGACATTATGC

NC_045512.2_19mer_win1_18100
18100
18118
571
ACACAGGCACCTACACACC
1774
GGTGTGTAGGTGCCTGTGT

NC_045512.2_19mer_win1_18101
18101
18119
572
CACAGGCACCTACACACCT
1775
AGGTGTGTAGGTGCCTGTG

NC_045512.2_19mer_win1_18102
18102
18120
573
ACAGGCACCTACACACCTC
1776
GAGGTGTGTAGGTGCCTGT

NC_045512.2_19mer_win1_18103
18103
18121
574
CAGGCACCTACACACCTCA
1777
TGAGGTGTGTAGGTGCCTG

NC_045512.2_19mer_win1_18104
18104
18122
575
AGGCACCTACACACCTCAG
1778
CTGAGGTGTGTAGGTGCCT

NC_045512.2_19mer_win1_18196
18196
18214
576
AGACTCATCTCTATGATGG
1779
CCATCATAGAGATGAGTCT

NC_045512.2_19mer_win1_18197
18197
18215
577
GACTCATCTCTATGATGGG
1780
CCCATCATAGAGATGAGTC

NC_045512.2_19mer_win1_18198
18198
18216
578
ACTCATCTCTATGATGGGT
1781
ACCCATCATAGAGATGAGT

NC_045512.2_19mer_win1_18199
18199
18217
579
CTCATCTCTATGATGGGTT
1782
AACCCATCATAGAGATGAG

NC_045512.2_19mer_win1_18200
18200
18218
580
TCATCTCTATGATGGGTTT
1783
AAACCCATCATAGAGATGA

NC_045512.2_19mer_win1_19618
19618
19636
581
CAGAGTTTAGAAAATGTGG
1784
CCACATTTTCTAAACTCTG

NC_045512.2_19mer_win1_19619
19619
19637
582
AGAGTTTAGAAAATGTGGC
1785
GCCACATTTTCTAAACTCT

NC_045512.2_19mer_win1_19620
19620
19638
583
GAGTTTAGAAAATGTGGCT
1786
AGCCACATTTTCTAAACTC

NC_045512.2_19mer_win1_19621
19621
19639
584
AGTTTAGAAAATGTGGCTT
1787
AAGCCACATTTTCTAAACT

NC_045512.2_19mer_win1_19783
19783
19801
585
TTTGAGCTTTGGGCTAAGC
1788
GCTTAGCCCAAAGCTCAAA

NC_045512.2_19mer_win1_19784
19784
19802
586
TTGAGCTTTGGGCTAAGCG
1789
CGCTTAGCCCAAAGCTCAA

NC_045512.2_19mer_win1_19831
19831
19849
587
ATACTCAATAATTTGGGTG
1790
CACCCAAATTATTGAGTAT

NC_045512.2_19mer_win1_19832
19832
19850
588
TACTCAATAATTTGGGTGT
1791
ACACCCAAATTATTGAGTA

NC_045512.2_19mer_win1_20107
20107
20125
589
AATGGAGTCACATTAATTG
1792
CAATTAATGTGACTCCATT

NC_045512.2_19mer_win1_20108
20108
20126
590
ATGGAGTCACATTAATTGG
1793
CCAATTAATGTGACTCCAT

NC_045512.2_19mer_win1_20109
20109
20127
591
TGGAGTCACATTAATTGGA
1794
TCCAATTAATGTGACTCCA

NC_045512.2_19mer_win1_20110
20110
20128
592
GGAGTCACATTAATTGGAG
1795
CTCCAATTAATGTGACTCC

NC_045512.2_19mer_win1_20111
20111
20129
593
GAGTCACATTAATTGGAGA
1796
TCTCCAATTAATGTGACTC

NC_045512.2_19mer_win1_20112
20112
20130
594
AGTCACATTAATTGGAGAA
1797
TTCTCCAATTAATGTGACT

NC_045512.2_19mer_win1_20776
20776
20794
595
ATAATGATGAATGTCGCAA
1798
TTGCGACATTCATCATTAT

NC_045512.2_19mer_win1_20777
20777
20795
596
TAATGATGAATGTCGCAAA
1799
TTTGCGACATTCATCATTA

NC_045512.2_19mer_win1_21502
21502
21520
597
ATTAGAGAAAACAACAGAG
1800
CTCTGTTGTTTTCTCTAAT

NC_045512.2_19mer_win1_21503
21503
21521
598
TTAGAGAAAACAACAGAGT
1801
ACTCTGTTGTTTTCTCTAA

NC_045512.2_19mer_win1_21504
21504
21522
599
TAGAGAAAACAACAGAGTT
1802
AACTCTGTTGTTTTCTCTA

NC_045512.2_19mer_win1_21505
21505
21523
600
AGAGAAAACAACAGAGTTG
1803
CAACTCTGTTGTTTTCTCT

NC_045512.2_19mer_win1_21506
21506
21524
601
GAGAAAACAACAGAGTTGT
1804
ACAACTCTGTTGTTTTCTC

NC_045512.2_19mer_win1_24302
24302
24320
602
AATGTTCTCTATGAGAACC
1805
GGTTCTCATAGAGAACATT

NC_045512.2_19mer_win1_24303
24303
24321
603
ATGTTCTCTATGAGAACCA
1806
TGGTTCTCATAGAGAACAT

NC_045512.2_19mer_win1_24304
24304
24322
604
TGTTCTCTATGAGAACCAA
1807
TTGGTTCTCATAGAGAACA

NC_045512.2_19mer_win1_24305
24305
24323
605
GTTCTCTATGAGAACCAAA
1808
TTTGGTTCTCATAGAGAAC

NC_045512.2_19mer_win1_24306
24306
24324
606
TTCTCTATGAGAACCAAAA
1809
TTTTGGTTCTCATAGAGAA

NC_045512.2_19mer_win1_24307
24307
24325
607
TCTCTATGAGAACCAAAAA
1810
TTTTTGGTTCTCATAGAGA

NC_045512.2_19mer_win1_24446
24446
24464
608
CTTGTTAAACAACTTAGCT
1811
AGCTAAGTTGTTTAACAAG

NC_045512.2_19mer_win1_24447
24447
24465
609
TTGTTAAACAACTTAGCTC
1812
GAGCTAAGTTGTTTAACAA

NC_045512.2_19mer_win1_24620
24620
24638
610
GCTTCTGCTAATCTTGCTG
1813
CAGCAAGATTAGCAGAAGC

NC_045512.2_19mer_win1_24621
24621
24639
611
CTTCTGCTAATCTTGCTGC
1814
GCAGCAAGATTAGCAGAAG

NC_045512.2_19mer_win1_24622
24622
24640
612
TTCTGCTAATCTTGCTGCT
1815
AGCAGCAAGATTAGCAGAA

NC_045512.2_19mer_win1_24623
24623
24641
613
TCTGCTAATCTTGCTGCTA
1816
TAGCAGCAAGATTAGCAGA

NC_045512.2_19mer_win1_24624
24624
24642
614
CTGCTAATCTTGCTGCTAC
1817
GTAGCAGCAAGATTAGCAG

NC_045512.2_19mer_win1_24625
24625
24643
615
TGCTAATCTTGCTGCTACT
1818
AGTAGCAGCAAGATTAGCA

NC_045512.2_19mer_win1_24626
24626
24644
616
GCTAATCTTGCTGCTACTA
1819
TAGTAGCAGCAAGATTAGC

NC_045512.2_19mer_win1_24627
24627
24645
617
CTAATCTTGCTGCTACTAA
1820
TTAGTAGCAGCAAGATTAG

NC_045512.2_19mer_win1_24628
24628
24646
618
TAATCTTGCTGCTACTAAA
1821
TTTAGTAGCAGCAAGATTA

NC_045512.2_19mer_win1_24629
24629
24647
619
AATCTTGCTGCTACTAAAA
1822
TTTTAGTAGCAGCAAGATT

NC_045512.2_19mer_win1_24630
24630
24648
620
ATCTTGCTGCTACTAAAAT
1823
ATTTTAGTAGCAGCAAGAT

NC_045512.2_19mer_win1_24631
24631
24649
621
TCTTGCTGCTACTAAAATG
1824
CATTTTAGTAGCAGCAAGA

NC_045512.2_19mer_win1_24632
24632
24650
622
CTTGCTGCTACTAAAATGT
1825
ACATTTTAGTAGCAGCAAG

NC_045512.2_19mer_win1_24633
24633
24651
623
TTGCTGCTACTAAAATGTC
1826
GACATTTTAGTAGCAGCAA

NC_045512.2_19mer_win1_24662
24662
24680
624
CTTGGACAATCAAAAAGAG
1827
CTCTTTTTGATTGTCCAAG

NC_045512.2_19mer_win1_24663
24663
24681
625
TTGGACAATCAAAAAGAGT
1828
ACTCTTTTTGATTGTCCAA

NC_045512.2_19mer_win1_24664
24664
24682
626
TGGACAATCAAAAAGAGTT
1829
AACTCTTTTTGATTGTCCA

NC_045512.2_19mer_win1_24665
24665
24683
627
GGACAATCAAAAAGAGTTG
1830
CAACTCTTTTTGATTGTCC

NC_045512.2_19mer_win1_24666
24666
24684
628
GACAATCAAAAAGAGTTGA
1831
TCAACTCTTTTTGATTGTC

NC_045512.2_19mer_win1_25034
25034
25052
629
AATCATACATCACCAGATG
1832
CATCTGGTGATGTATGATT

NC_045512.2_19mer_win1_25035
25035
25053
630
ATCATACATCACCAGATGT
1833
ACATCTGGTGATGTATGAT

NC_045512.2_19mer_win1_25038
25038
25056
633
ATACATCACCAGATGTTGA
1836
TCAACATCTGGTGATGTAT

NC_045512.2_19mer_win1_25039
25039
25057
634
TACATCACCAGATGTTGAT
1837
ATCAACATCTGGTGATGTA

NC_045512.2_19mer_win1_25104
25104
25122
635
AAGAAATTGACCGCCTCAA
1838
TTGAGGCGGTCAATTTCTT

NC_045512.2_19mer_win1_25105
25105
25123
636
AGAAATTGACCGCCTCAAT
1839
ATTGAGGCGGTCAATTTCT

NC_045512.2_19mer_win1_25106
25106
25124
637
GAAATTGACCGCCTCAATG
1840
CATTGAGGCGGTCAATTTC

NC_045512.2_19mer_win1_25107
25107
25125
638
AAATTGACCGCCTCAATGA
1841
TCATTGAGGCGGTCAATTT

NC_045512.2_19mer_win1_25108
25108
25126
639
AATTGACCGCCTCAATGAG
1842
CTCATTGAGGCGGTCAATT

NC_045512.2_19mer_win1_25109
25109
25127
640
ATTGACCGCCTCAATGAGG
1843
CCTCATTGAGGCGGTCAAT

NC_045512.2_19mer_win1_25110
25110
25128
641
TTGACCGCCTCAATGAGGT
1844
ACCTCATTGAGGCGGTCAA

NC_045512.2_19mer_win1_25364
25364
25382
642
GTCAAATTACATTACACAT
1845
ATGTGTAATGTAATTTGAC

NC_045512.2_19mer_win1_25365
25365
25383
643
TCAAATTACATTACACATA
1846
TATGTGTAATGTAATTTGA

NC_045512.2_19mer_win1_25366
25366
25384
644
CAAATTACATTACACATAA
1847
TTATGTGTAATGTAATTTG

NC_045512.2_19mer_win1_25367
25367
25385
645
AAATTACATTACACATAAA
1848
TTTATGTGTAATGTAATTT

NC_045512.2_19mer_win1_25368
25368
25386
646
AATTACATTACACATAAAC
1849
GTTTATGTGTAATGTAATT

NC_045512.2_19mer_win1_25369
25369
25387
647
ATTACATTACACATAAACG
1850
CGTTTATGTGTAATGTAAT

NC_045512.2_19mer_win1_25502
25502
25520
648
TACAAGCCTCACTCCCTTT
1851
AAAGGGAGTGAGGCTTGTA

NC_045512.2_19mer_win1_25503
25503
25521
649
ACAAGCCTCACTCCCTTTC
1852
GAAAGGGAGTGAGGCTTGT

NC_045512.2_19mer_win1_25504
25504
25522
650
CAAGCCTCACTCCCTTTCG
1853
CGAAAGGGAGTGAGGCTTG

NC_045512.2_19mer_win1_25505
25505
25523
651
AAGCCTCACTCCCTTTCGG
1854
CCGAAAGGGAGTGAGGCTT

NC_045512.2_19mer_win1_25506
25506
25524
652
AGCCTCACTCCCTTTCGGA
1855
TCCGAAAGGGAGTGAGGCT

NC_045512.2_19mer_win1_25507
25507
25525
653
GCCTCACTCCCTTTCGGAT
1856
ATCCGAAAGGGAGTGAGGC

NC_045512.2_19mer_win1_25508
25508
25526
654
CCTCACTCCCTTTCGGATG
1857
CATCCGAAAGGGAGTGAGG

NC_045512.2_19mer_win1_25509
25509
25527
655
CTCACTCCCTTTCGGATGG
1858
CCATCCGAAAGGGAGTGAG

NC_045512.2_19mer_win1_25510
25510
25528
656
TCACTCCCTTTCGGATGGC
1859
GCCATCCGAAAGGGAGTGA

NC_045512.2_19mer_win1_25511
25511
25529
657
CACTCCCTTTCGGATGGCT
1860
AGCCATCCGAAAGGGAGTG

NC_045512.2_19mer_win1_25512
25512
25530
658
ACTCCCTTTCGGATGGCTT
1861
AAGCCATCCGAAAGGGAGT

NC_045512.2_19mer_win1_26191
26191
26209
659
CCGACGACGACTACTAGCG
1862
CGCTAGTAGTCGTCGTCGG

NC_045512.2_19mer_win1_26192
26192
26210
660
CGACGACGACTACTAGCGT
1863
ACGCTAGTAGTCGTCGTCG

NC_045512.2_19mer_win1_26193
26193
26211
661
GACGACGACTACTAGCGTG
1864
CACGCTAGTAGTCGTCGTC

NC_045512.2_19mer_win1_26194
26194
26212
662
ACGACGACTACTAGCGTGC
1865
GCACGCTAGTAGTCGTCGT

NC_045512.2_19mer_win1_26195
26195
26213
663
CGACGACTACTAGCGTGCC
1866
GGCACGCTAGTAGTCGTCG

NC_045512.2_19mer_win1_26196
26196
26214
664
GACGACTACTAGCGTGCCT
1867
AGGCACGCTAGTAGTCGTC

NC_045512.2_19mer_win1_26197
26197
26215
665
ACGACTACTAGCGTGCCTT
1868
AAGGCACGCTAGTAGTCGT

NC_045512.2_19mer_win1_26198
26198
26216
666
CGACTACTAGCGTGCCTTT
1869
AAAGGCACGCTAGTAGTCG

NC_045512.2_19mer_win1_26199
26199
26217
667
GACTACTAGCGTGCCTTTG
1870
CAAAGGCACGCTAGTAGTC

NC_045512.2_19mer_win1_26200
26200
26218
668
ACTACTAGCGTGCCTTTGT
1871
ACAAAGGCACGCTAGTAGT

NC_045512.2_19mer_win1_26201
26201
26219
669
CTACTAGCGTGCCTTTGTA
1872
TACAAAGGCACGCTAGTAG

NC_045512.2_19mer_win1_26202
26202
26220
670
TACTAGCGTGCCTTTGTAA
1873
TTACAAAGGCACGCTAGTA

NC_045512.2_19mer_win1_26203
26203
26221
671
ACTAGCGTGCCTTTGTAAG
1874
CTTACAAAGGCACGCTAGT

NC_045512.2_19mer_win1_26204
26204
26222
672
CTAGCGTGCCTTTGTAAGC
1875
GCTTACAAAGGCACGCTAG

NC_045512.2_19mer_win1_26205
26205
26223
673
TAGCGTGCCTTTGTAAGCA
1876
TGCTTACAAAGGCACGCTA

NC_045512.2_19mer_win1_26206
26206
26224
674
AGCGTGCCTTTGTAAGCAC
1877
GTGCTTACAAAGGCACGCT

NC_045512.2_19mer_win1_26207
26207
26225
675
GCGTGCCTTTGTAAGCACA
1878
TGTGCTTACAAAGGCACGC

NC_045512.2_19mer_win1_26208
26208
26226
676
CGTGCCTTTGTAAGCACAA
1879
TTGTGCTTACAAAGGCACG

NC_045512.2_19mer_win1_26209
26209
26227
677
GTGCCTTTGTAAGCACAAG
1880
CTTGTGCTTACAAAGGCAC

NC_045512.2_19mer_win1_26232
26232
26250
678
TGAGTACGAACTTATGTAC
1881
GTACATAAGTTCGTACTCA

NC_045512.2_19mer_win1_26233
26233
26251
679
GAGTACGAACTTATGTACT
1882
AGTACATAAGTTCGTACTC

NC_045512.2_19mer_win1_26234
26234
26252
680
AGTACGAACTTATGTACTC
1883
GAGTACATAAGTTCGTACT

NC_045512.2_19mer_win1_26235
26235
26253
681
GTACGAACTTATGTACTCA
1884
TGAGTACATAAGTTCGTAC

NC_045512.2_19mer_win1_26236
26236
26254
682
TACGAACTTATGTACTCAT
1885
ATGAGTACATAAGTTCGTA

NC_045512.2_19mer_win1_26237
26237
26255
683
ACGAACTTATGTACTCATT
1886
AATGAGTACATAAGTTCGT

NC_045512.2_19mer_win1_26238
26238
26256
684
CGAACTTATGTACTCATTC
1887
GAATGAGTACATAAGTTCG

NC_045512.2_19mer_win1_26239
26239
26257
685
GAACTTATGTACTCATTCG
1888
CGAATGAGTACATAAGTTC

NC_045512.2_19mer_win1_26240
26240
26258
686
AACTTATGTACTCATTCGT
1889
ACGAATGAGTACATAAGTT

NC_045512.2_19mer_win1_26241
26241
26259
687
ACTTATGTACTCATTCGTT
1890
AACGAATGAGTACATAAGT

NC_045512.2_19mer_win1_26242
26242
26260
688
CTTATGTACTCATTCGTTT
1891
AAACGAATGAGTACATAAG

NC_045512.2_19mer_win1_26243
26243
26261
689
TTATGTACTCATTCGTTTC
1892
GAAACGAATGAGTACATAA

NC_045512.2_19mer_win1_26244
26244
26262
690
TATGTACTCATTCGTTTCG
1893
CGAAACGAATGAGTACATA

NC_045512.2_19mer_win1_26245
26245
26263
691
ATGTACTCATTCGTTTCGG
1894
CCGAAACGAATGAGTACAT

NC_045512.2_19mer_win1_26246
26246
26264
692
TGTACTCATTCGTTTCGGA
1895
TCCGAAACGAATGAGTACA

NC_045512.2_19mer_win1_26247
26247
26265
693
GTACTCATTCGTTTCGGAA
1896
TTCCGAAACGAATGAGTAC

NC_045512.2_19mer_win1_26248
26248
26266
694
TACTCATTCGTTTCGGAAG
1897
CTTCCGAAACGAATGAGTA

NC_045512.2_19mer_win1_26249
26249
26267
695
ACTCATTCGTTTCGGAAGA
1898
TCTTCCGAAACGAATGAGT

NC_045512.2_19mer_win1_26269
26269
26287
696
ACAGGTACGTTAATAGTTA
1899
TAACTATTAACGTACCTGT

NC_045512.2_19mer_win1_26270
26270
26288
697
CAGGTACGTTAATAGTTAA
1900
TTAACTATTAACGTACCTG

NC_045512.2_19mer_win1_26271
26271
26289
698
AGGTACGTTAATAGTTAAT
1901
ATTAACTATTAACGTACCT

NC_045512.2_19mer_win1_26272
26272
26290
699
GGTACGTTAATAGTTAATA
1902
TATTAACTATTAACGTACC

NC_045512.2_19mer_win1_26273
26273
26291
700
GTACGTTAATAGTTAATAG
1903
CTATTAACTATTAACGTAC

NC_045512.2_19mer_win1_26274
26274
26292
701
TACGTTAATAGTTAATAGC
1904
GCTATTAACTATTAACGTA

NC_045512.2_19mer_win1_26275
26275
26293
702
ACGTTAATAGTTAATAGCG
1905
CGCTATTAACTATTAACGT

NC_045512.2_19mer_win1_26276
26276
26294
703
CGTTAATAGTTAATAGCGT
1906
ACGCTATTAACTATTAACG

NC_045512.2_19mer_win1_26277
26277
26295
704
GTTAATAGTTAATAGCGTA
1907
TACGCTATTAACTATTAAC

NC_045512.2_19mer_win1_26278
26278
26296
705
TTAATAGTTAATAGCGTAC
1908
GTACGCTATTAACTATTAA

NC_045512.2_19mer_win1_26279
26279
26297
706
TAATAGTTAATAGCGTACT
1909
AGTACGCTATTAACTATTA

NC_045512.2_19mer_win1_26280
26280
26298
707
AATAGTTAATAGCGTACTT
1910
AAGTACGCTATTAACTATT

NC_045512.2_19mer_win1_26281
26281
26299
708
ATAGTTAATAGCGTACTTC
1911
GAAGTACGCTATTAACTAT

NC_045512.2_19mer_win1_26282
26282
26300
709
TAGTTAATAGCGTACTTCT
1912
AGAAGTACGCTATTAACTA

NC_045512.2_19mer_win1_26283
26283
26301
710
AGTTAATAGCGTACTTCTT
1913
AAGAAGTACGCTATTAACT

NC_045512.2_19mer_win1_26284
26284
26302
711
GTTAATAGCGTACTTCTTT
1914
AAAGAAGTACGCTATTAAC

NC_045512.2_19mer_win1_26285
26285
26303
712
TTAATAGCGTACTTCTTTT
1915
AAAAGAAGTACGCTATTAA

NC_045512.2_19mer_win1_26286
26286
26304
713
TAATAGCGTACTTCTTTTT
1916
AAAAAGAAGTACGCTATTA

NC_045512.2_19mer_win1_26287
26287
26305
714
AATAGCGTACTTCTTTTTC
1917
GAAAAAGAAGTACGCTATT

NC_045512.2_19mer_win1_26288
26288
26306
715
ATAGCGTACTTCTTTTTCT
1918
AGAAAAAGAAGTACGCTAT

NC_045512.2_19mer_win1_26289
26289
26307
716
TAGCGTACTTCTTTTTCTT
1919
AAGAAAAAGAAGTACGCTA

NC_045512.2_19mer_win1_26290
26290
26308
717
AGCGTACTTCTTTTTCTTG
1920
CAAGAAAAAGAAGTACGCT

NC_045512.2_19mer_win1_26291
26291
26309
718
GCGTACTTCTTTTTCTTGC
1921
GCAAGAAAAAGAAGTACGC

NC_045512.2_19mer_winl_26292
26292
26310
719
CGTACTTCTTTTTCTTGCT
1922
AGCAAGAAAAAGAAGTACG

NC_045512.2_19mer_winl_26293
26293
26311
720
GTACTTCTTTTTCTTGCTT
1923
AAGCAAGAAAAAGAAGTAC

NC_045512.2_19mer_winl_26294
26294
26312
721
TACTTCTTTTTCTTGCTTT
1924
AAAGCAAGAAAAAGAAGTA

NC_045512.2_19mer_winl_26295
26295
26313
722
ACTTCTTTTTCTTGCTTTC
1925
GAAAGCAAGAAAAAGAAGT

NC_045512.2_19mer_winl_26296
26296
26314
723
CTTCTTTTTCTTGCTTTCG
1926
CGAAAGCAAGAAAAAGAAG

NC_045512.2_19mer_winl_26297
26297
26315
724
TTCTTTTTCTTGCTTTCGT
1927
ACGAAAGCAAGAAAAAGAA

NC_045512.2_19mer_winl_26298
26298
26316
725
TCTTTTTCTTGCTTTCGTG
1928
CACGAAAGCAAGAAAAAGA

NC_045512.2_19mer_winl_26299
26299
26317
726
CTTTTTCTTGCTTTCGTGG
1929
CCACGAAAGCAAGAAAAAG

NC_045512.2_19mer_winl_26300
26300
26318
727
TTTTTCTTGCTTTCGTGGT
1930
ACCACGAAAGCAAGAAAAA

NC_045512.2_19mer_winl_26301
26301
26319
728
TTTTCTTGCTTTCGTGGTA
1931
TACCACGAAAGCAAGAAAA

NC_045512.2_19mer_winl_26302
26302
26320
729
TTTCTTGCTTTCGTGGTAT
1932
ATACCACGAAAGCAAGAAA

NC_045512.2_19mer_winl_26303
26303
26321
730
TTCTTGCTTTCGTGGTATT
1933
AATACCACGAAAGCAAGAA

NC_045512.2_19mer_winl_26304
26304
26322
731
TCTTGCTTTCGTGGTATTC
1934
GAATACCACGAAAGCAAGA

NC_045512.2_19mer_winl_26305
26305
26323
732
CTTGCTTTCGTGGTATTCT
1935
AGAATACCACGAAAGCAAG

NC_045512.2_19mer_winl_26306
26306
26324
733
TTGCTTTCGTGGTATTCTT
1936
AAGAATACCACGAAAGCAA

NC_045512.2_19mer_winl_26307
26307
26325
734
TGCTTTCGTGGTATTCTTG
1937
CAAGAATACCACGAAAGCA

NC_045512.2_19mer_winl_26308
26308
26326
735
GCTTTCGTGGTATTCTTGC
1938
GCAAGAATACCACGAAAGC

NC_045512.2_19mer_winl_26309
26309
26327
736
CTTTCGTGGTATTCTTGCT
1939
AGCAAGAATACCACGAAAG

NC_045512.2_19mer_winl_26310
26310
26328
737
TTTCGTGGTATTCTTGCTA
1940
TAGCAAGAATACCACGAAA

NC_045512.2_19mer_winl_26311
26311
26329
738
TTCGTGGTATTCTTGCTAG
1941
CTAGCAAGAATACCACGAA

NC_045512.2_19mer_win1_26312
26312
26330
739
TCGTGGTATTCTTGCTAGT
1942
ACTAGCAAGAATACCACGA

NC_045512.2_19mer_win1_26332
26332
26350
740
ACACTAGCCATCCTTACTG
1943
CAGTAAGGATGGCTAGTGT

NC_045512.2_19mer_win1_26333
26333
26351
741
CACTAGCCATCCTTACTGC
1944
GCAGTAAGGATGGCTAGTG

NC_045512.2_19mer_win1_26334
26334
26352
742
ACTAGCCATCCTTACTGCG
1945
CGCAGTAAGGATGGCTAGT

NC_045512.2_19mer_win1_26335
26335
26353
743
CTAGCCATCCTTACTGCGC
1946
GCGCAGTAAGGATGGCTAG

NC_045512.2_19mer_win1_26336
26336
26354
744
TAGCCATCCTTACTGCGCT
1947
AGCGCAGTAAGGATGGCTA

NC_045512.2_19mer_win1_26337
26337
26355
745
AGCCATCCTTACTGCGCTT
1948
AAGCGCAGTAAGGATGGCT

NC_045512.2_19mer_win1_26338
26338
26356
746
GCCATCCTTACTGCGCTTC
1949
GAAGCGCAGTAAGGATGGC

NC_045512.2_19mer_win1_26339
26339
26357
747
CCATCCTTACTGCGCTTCG
1950
CGAAGCGCAGTAAGGATGG

NC_045512.2_19mer_win1_26340
26340
26358
748
CATCCTTACTGCGCTTCGA
1951
TCGAAGCGCAGTAAGGATG

NC_045512.2_19mer_win1_26341
26341
26359
749
ATCCTTACTGCGCTTCGAT
1952
ATCGAAGCGCAGTAAGGAT

NC_045512.2_19mer_win1_26342
26342
26360
750
TCCTTACTGCGCTTCGATT
1953
AATCGAAGCGCAGTAAGGA

NC_045512.2_19mer_win1_26343
26343
26361
751
CCTTACTGCGCTTCGATTG
1954
CAATCGAAGCGCAGTAAGG

NC_045512.2_19mer_win1_26344
26344
26362
752
CTTACTGCGCTTCGATTGT
1955
ACAATCGAAGCGCAGTAAG

NC_045512.2_19mer_win1_26345
26345
26363
753
TTACTGCGCTTCGATTGTG
1956
CACAATCGAAGCGCAGTAA

NC_045512.2_19mer_win1_26346
26346
26364
754
TACTGCGCTTCGATTGTGT
1957
ACACAATCGAAGCGCAGTA

NC_045512.2_19mer_win1_26347
26347
26365
755
ACTGCGCTTCGATTGTGTG
1958
CACACAATCGAAGCGCAGT

NC_045512.2_19mer_win1_26348
26348
26366
756
CTGCGCTTCGATTGTGTGC
1959
GCACACAATCGAAGCGCAG

NC_045512.2_19mer_win1_26349
26349
26367
757
TGCGCTTCGATTGTGTGCG
1960
CGCACACAATCGAAGCGCA

NC_045512.2_19mer_win1_26350
26350
26368
758
GCGCTTCGATTGTGTGCGT
1961
ACGCACACAATCGAAGCGC

NC_045512.2_19mer_win1_26351
26351
26369
759
CGCTTCGATTGTGTGCGTA
1962
TACGCACACAATCGAAGCG

NC_045512.2_19mer_win1_26352
26352
26370
760
GCTTCGATTGTGTGCGTAC
1963
GTACGCACACAATCGAAGC

NC_045512.2_19mer_win1_26353
26353
26371
761
CTTCGATTGTGTGCGTACT
1964
AGTACGCACACAATCGAAG

NC_045512.2_19mer_win1_26354
26354
26372
762
TTCGATTGTGTGCGTACTG
1965
CAGTACGCACACAATCGAA

NC_045512.2_19mer_win1_26355
26355
26373
763
TCGATTGTGTGCGTACTGC
1966
GCAGTACGCACACAATCGA

NC_045512.2_19mer_win1_26356
26356
26374
764
CGATTGTGTGCGTACTGCT
1967
AGCAGTACGCACACAATCG

NC_045512.2_19mer_win1_26357
26357
26375
765
GATTGTGTGCGTACTGCTG
1968
CAGCAGTACGCACACAATC

NC_045512.2_19mer_win1_26358
26358
26376
766
ATTGTGTGCGTACTGCTGC
1969
GCAGCAGTACGCACACAAT

NC_045512.2_19mer_win1_26359
26359
26377
767
TTGTGTGCGTACTGCTGCA
1970
TGCAGCAGTACGCACACAA

NC_045512.2_19mer_win1_26360
26360
26378
768
TGTGTGCGTACTGCTGCAA
1971
TTGCAGCAGTACGCACACA

NC_045512.2_19mer_win1_26361
26361
26379
769
GTGTGCGTACTGCTGCAAT
1972
ATTGCAGCAGTACGCACAC

NC_045512.2_19mer_win1_26362
26362
26380
770
TGTGCGTACTGCTGCAATA
1973
TATTGCAGCAGTACGCACA

NC_045512.2_19mer_win1_26363
26363
26381
771
GTGCGTACTGCTGCAATAT
1974
ATATTGCAGCAGTACGCAC

NC_045512.2_19mer_win1_26364
26364
26382
772
TGCGTACTGCTGCAATATT
1975
AATATTGCAGCAGTACGCA

NC_045512.2_19mer_win1_26365
26365
26383
773
GCGTACTGCTGCAATATTG
1976
CAATATTGCAGCAGTACGC

NC_045512.2_19mer_win1_26366
26366
26384
774
CGTACTGCTGCAATATTGT
1977
ACAATATTGCAGCAGTACG

NC_045512.2_19mer_win1_26367
26367
26385
775
GTACTGCTGCAATATTGTT
1978
AACAATATTGCAGCAGTAC

NC_045512.2_19mer_win1_26368
26368
26386
776
TACTGCTGCAATATTGTTA
1979
TAACAATATTGCAGCAGTA

NC_045512.2_19mer_win1_26369
26369
26387
777
ACTGCTGCAATATTGTTAA
1980
TTAACAATATTGCAGCAGT

NC_045512.2_19mer_win1_26370
26370
26388
778
CTGCTGCAATATTGTTAAC
1981
GTTAACAATATTGCAGCAG

NC_045512.2_19mer_win1_26371
26371
26389
779
TGCTGCAATATTGTTAACG
1982
CGTTAACAATATTGCAGCA

NC_045512.2_19mer_win1_26372
26372
26390
780
GCTGCAATATTGTTAACGT
1983
ACGTTAACAATATTGCAGC

NC_045512.2_19mer_win1_26373
26373
26391
781
CTGCAATATTGTTAACGTG
1984
CACGTTAACAATATTGCAG

NC_045512.2_19mer_win1_26374
26374
26392
782
TGCAATATTGTTAACGTGA
1985
TCACGTTAACAATATTGCA

NC_045512.2_19mer_win1_26375
26375
26393
783
GCAATATTGTTAACGTGAG
1986
CTCACGTTAACAATATTGC

NC_045512.2_19mer_win1_26376
26376
26394
784
CAATATTGTTAACGTGAGT
1987
ACTCACGTTAACAATATTG

NC_045512.2_19mer_win1_26450
26450
26468
785
GAGTTCCTGATCTTCTGGT
1988
ACCAGAAGATCAGGAACTC

NC_045512.2_19mer_win1_26451
26451
26469
786
AGTTCCTGATCTTCTGGTC
1989
GACCAGAAGATCAGGAACT

NC_045512.2_19mer_win1_26452
26452
26470
787
GTTCCTGATCTTCTGGTCT
1990
AGACCAGAAGATCAGGAAC

NC_045512.2_19mer_win1_26453
26453
26471
788
TTCCTGATCTTCTGGTCTA
1991
TAGACCAGAAGATCAGGAA

NC_045512.2_19mer_win1_26454
26454
26472
789
TCCTGATCTTCTGGTCTAA
1992
TTAGACCAGAAGATCAGGA

NC_045512.2_19mer_win1_26455
26455
26473
790
CCTGATCTTCTGGTCTAAA
1993
TTTAGACCAGAAGATCAGG

NC_045512.2_19mer_win1_26456
26456
26474
791
CTGATCTTCTGGTCTAAAC
1994
GTTTAGACCAGAAGATCAG

NC_045512.2_19mer_win1_26457
26457
26475
792
TGATCTTCTGGTCTAAACG
1995
CGTTTAGACCAGAAGATCA

NC_045512.2_19mer_win1_26458
26458
26476
793
GATCTTCTGGTCTAAACGA
1996
TCGTTTAGACCAGAAGATC

NC_045512.2_19mer_win1_26459
26459
26477
794
ATCTTCTGGTCTAAACGAA
1997
TTCGTTTAGACCAGAAGAT

NC_045512.2_19mer_win1_26460
26460
26478
795
TCTTCTGGTCTAAACGAAC
1998
GTTCGTTTAGACCAGAAGA

NC_045512.2_19mer_win1_26461
26461
26479
796
CTTCTGGTCTAAACGAACT
1999
AGTTCGTTTAGACCAGAAG

NC_045512.2_19mer_win1_26462
26462
26480
797
TTCTGGTCTAAACGAACTA
2000
TAGTTCGTTTAGACCAGAA

NC_045512.2_19mer_win1_26463
26463
26481
798
TCTGGTCTAAACGAACTAA
2001
TTAGTTCGTTTAGACCAGA

NC_045512.2_19mer_win1_26574
26574
26592
799
GAACAATGGAACCTAGTAA
2002
TTACTAGGTTCCATTGTTC

NC_045512.2_19mer_win1_26575
26575
26593
800
AACAATGGAACCTAGTAAT
2003
ATTACTAGGTTCCATTGTT

NC_045512.2_19mer_win1_26576
26576
26594
801
ACAATGGAACCTAGTAATA
2004
TATTACTAGGTTCCATTGT

NC_045512.2_19mer_win1_26577
26577
26595
802
CAATGGAACCTAGTAATAG
2005
CTATTACTAGGTTCCATTG

NC_045512.2_19mer_win1_26578
26578
26596
803
AATGGAACCTAGTAATAGG
2006
CCTATTACTAGGTTCCATT

NC_045512.2_19mer_win1_26579
26579
26597
804
ATGGAACCTAGTAATAGGT
2007
ACCTATTACTAGGTTCCAT

NC_045512.2_19mer_win1_26580
26580
26598
805
TGGAACCTAGTAATAGGTT
2008
AACCTATTACTAGGTTCCA

NC_045512.2_19mer_win1_26581
26581
26599
806
GGAACCTAGTAATAGGTTT
2009
AAACCTATTACTAGGTTCC

NC_045512.2_19mer_win1_26582
26582
26600
807
GAACCTAGTAATAGGTTTC
2010
GAAACCTATTACTAGGTTC

NC_045512.2_19mer_win1_27033
27033
27051
808
GCTACATCACGAACGCTTT
2011
AAAGCGTTCGTGATGTAGC

NC_045512.2_19mer_win1_27034
27034
27052
809
CTACATCACGAACGCTTTC
2012
GAAAGCGTTCGTGATGTAG

NC_045512.2_19mer_win1_27035
27035
27053
810
TACATCACGAACGCTTTCT
2013
AGAAAGCGTTCGTGATGTA

NC_045512.2_19mer_win1_27036
27036
27054
811
ACATCACGAACGCTTTCTT
2014
AAGAAAGCGTTCGTGATGT

NC_045512.2_19mer_win1_27037
27037
27055
812
CATCACGAACGCTTTCTTA
2015
TAAGAAAGCGTTCGTGATG

NC_045512.2_19mer_win1_27038
27038
27056
813
ATCACGAACGCTTTCTTAT
2016
ATAAGAAAGCGTTCGTGAT

NC_045512.2_19mer_win1_27039
27039
27057
814
TCACGAACGCTTTCTTATT
2017
AATAAGAAAGCGTTCGTGA

NC_045512.2_19mer_win1_27040
27040
27058
815
CACGAACGCTTTCTTATTA
2018
TAATAAGAAAGCGTTCGTG

NC_045512.2_19mer_win1_27041
27041
27059
816
ACGAACGCTTTCTTATTAC
2019
GTAATAAGAAAGCGTTCGT

NC_045512.2_19mer_win1_27042
27042
27060
817
CGAACGCTTTCTTATTACA
2020
TGTAATAAGAAAGCGTTCG

NC_045512.2_19mer_win1_27043
27043
27061
818
GAACGCTTTCTTATTACAA
2021
TTGTAATAAGAAAGCGTTC

NC_045512.2_19mer_win1_27044
27044
27062
819
AACGCTTTCTTATTACAAA
2022
TTTGTAATAAGAAAGCGTT

NC_045512.2_19mer_win1_27045
27045
27063
820
ACGCTTTCTTATTACAAAT
2023
ATTTGTAATAAGAAAGCGT

NC_045512.2_19mer_win1_27046
27046
27064
821
CGCTTTCTTATTACAAATT
2024
AATTTGTAATAAGAAAGCG

NC_045512.2_19mer_win1_27093
27093
27111
822
TCAGGTTTTGCTGCATACA
2025
TGTATGCAGCAAAACCTGA

NC_045512.2_19mer_win1_27183
27183
27201
823
GTACAGTAAGTGACAACAG
2026
CTGTTGTCACTTACTGTAC

NC_045512.2_19mer_win1_27184
27184
27202
824
TACAGTAAGTGACAACAGA
2027
TCTGTTGTCACTTACTGTA

NC_045512.2_19mer_win1_27185
27185
27203
825
ACAGTAAGTGACAACAGAT
2028
ATCTGTTGTCACTTACTGT

NC_045512.2_19mer_win1_27186
27186
27204
826
CAGTAAGTGACAACAGATG
2029
CATCTGTTGTCACTTACTG

NC_045512.2_19mer_win1_27187
27187
27205
827
AGTAAGTGACAACAGATGT
2030
ACATCTGTTGTCACTTACT

NC_045512.2_19mer_win1_27188
27188
27206
828
GTAAGTGACAACAGATGTT
2031
AACATCTGTTGTCACTTAC

NC_045512.2_19mer_win1_27189
27189
27207
829
TAAGTGACAACAGATGTTT
2032
AAACATCTGTTGTCACTTA

NC_045512.2_19mer_win1_27190
27190
27208
830
AAGTGACAACAGATGTTTC
2033
GAAACATCTGTTGTCACTT

NC_045512.2_19mer_win1_27191
27191
27209
831
AGTGACAACAGATGTTTCA
2034
TGAAACATCTGTTGTCACT

NC_045512.2_19mer_win1_27192
27192
27210
832
GTGACAACAGATGTTTCAT
2035
ATGAAACATCTGTTGTCAC

NC_045512.2_19mer_win1_27193
27193
27211
833
TGACAACAGATGTTTCATC
2036
GATGAAACATCTGTTGTCA

NC_045512.2_19mer_win1_27194
27194
27212
834
GACAACAGATGTTTCATCT
2037
AGATGAAACATCTGTTGTC

NC_045512.2_19mer_win1_27382
27382
27400
835
GATTAAACGAACATGAAAA
2038
TTTTCATGTTCGTTTAATC

NC_045512.2_19mer_win1_27383
27383
27401
836
ATTAAACGAACATGAAAAT
2039
ATTTTCATGTTCGTTTAAT

NC_045512.2_19mer_win1_27384
27384
27402
837
TTAAACGAACATGAAAATT
2040
AATTTTCATGTTCGTTTAA

NC_045512.2_19mer_win1_27385
27385
27403
838
TAAACGAACATGAAAATTA
2041
TAATTTTCATGTTCGTTTA

NC_045512.2_19mer_win1_27386
27386
27404
839
AAACGAACATGAAAATTAT
2042
ATAATTTTCATGTTCGTTT

NC_045512.2_19mer_win1_27387
27387
27405
840
AACGAACATGAAAATTATT
2043
AATAATTTTCATGTTCGTT

NC_045512.2_19mer_win1_27388
27388
27406
841
ACGAACATGAAAATTATTC
2044
GAATAATTTTCATGTTCGT

NC_045512.2_19mer_win1_27389
27389
27407
842
CGAACATGAAAATTATTCT
2045
AGAATAATTTTCATGTTCG

NC_045512.2_19mer_win1_27511
27511
27529
843
TACGAGGGCAATTCACCAT
2046
ATGGTGAATTGCCCTCGTA

NC_045512.2_19mer_win1_27512
27512
27530
844
ACGAGGGCAATTCACCATT
2047
AATGGTGAATTGCCCTCGT

NC_045512.2_19mer_win1_27513
27513
27531
845
CGAGGGCAATTCACCATTT
2048
AAATGGTGAATTGCCCTCG

NC_045512.2_19mer_win1_27514
27514
27532
846
GAGGGCAATTCACCATTTC
2049
GAAATGGTGAATTGCCCTC

NC_045512.2_19mer_win1_27515
27515
27533
847
AGGGCAATTCACCATTTCA
2050
TGAAATGGTGAATTGCCCT

NC_045512.2_19mer_win1_27771
27771
27789
848
TTAATTGACTTCTATTTGT
2051
ACAAATAGAAGTCAATTAA

NC_045512.2_19mer_win1_27772
27772
27790
849
TAATTGACTTCTATTTGTG
2052
CACAAATAGAAGTCAATTA

NC_045512.2_19mer_win1_27773
27773
27791
850
AATTGACTTCTATTTGTGC
2053
GCACAAATAGAAGTCAATT

NC_045512.2_19mer_win1_27774
27774
27792
851
ATTGACTTCTATTTGTGCT
2054
AGCACAAATAGAAGTCAAT

NC_045512.2_19mer_win1_27775
27775
27793
852
TTGACTTCTATTTGTGCTT
2055
AAGCACAAATAGAAGTCAA

NC_045512.2_19mer_win1_27776
27776
27794
853
TGACTTCTATTTGTGCTTT
2056
AAAGCACAAATAGAAGTCA

NC_045512.2_19mer_win1_27777
27777
27795
854
GACTTCTATTTGTGCTTTT
2057
AAAAGCACAAATAGAAGTC

NC_045512.2_19mer_win1_27778
27778
27796
855
ACTTCTATTTGTGCTTTTT
2058
AAAAAGCACAAATAGAAGT

NC_045512.2_19mer_win1_27779
27779
27797
856
CTTCTATTTGTGCTTTTTA
2059
TAAAAAGCACAAATAGAAG

NC_045512.2_19mer_win1_27780
27780
27798
857
TTCTATTTGTGCTTTTTAG
2060
CTAAAAAGCACAAATAGAA

NC_045512.2_19mer_win1_27781
27781
27799
858
TCTATTTGTGCTTTTTAGC
2061
GCTAAAAAGCACAAATAGA

NC_045512.2_19mer_win1_27782
27782
27800
859
CTATTTGTGCTTTTTAGCC
2062
GGCTAAAAAGCACAAATAG

NC_045512.2_19mer_win1_27783
27783
27801
860
TATTTGTGCTTTTTAGCCT
2063
AGGCTAAAAAGCACAAATA

NC_045512.2_19mer_win1_27784
27784
27802
861
ATTTGTGCTTTTTAGCCTT
2064
AAGGCTAAAAAGCACAAAT

NC_045512.2_19mer_win1_27785
27785
27803
862
TTTGTGCTTTTTAGCCTTT
2065
AAAGGCTAAAAAGCACAAA

NC_045512.2_19mer_win1_27786
27786
27804
863
TTGTGCTTTTTAGCCTTTC
2066
GAAAGGCTAAAAAGCACAA

NC_045512.2_19mer_win1_27787
27787
27805
864
TGTGCTTTTTAGCCTTTCT
2067
AGAAAGGCTAAAAAGCACA

NC_045512.2_19mer_win1_27788
27788
27806
865
GTGCTTTTTAGCCTTTCTG
2068
CAGAAAGGCTAAAAAGCAC

NC_045512.2_19mer_win1_27789
27789
27807
866
TGCTTTTTAGCCTTTCTGC
2069
GCAGAAAGGCTAAAAAGCA

NC_045512.2_19mer_win1_27790
27790
27808
867
GCTTTTTAGCCTTTCTGCT
2070
AGCAGAAAGGCTAAAAAGC

NC_045512.2_19mer_win1_27791
27791
27809
868
CTTTTTAGCCTTTCTGCTA
2071
TAGCAGAAAGGCTAAAAAG

NC_045512.2_19mer_win1_27792
27792
27810
869
TTTTTAGCCTTTCTGCTAT
2072
ATAGCAGAAAGGCTAAAAA

NC_045512.2_19mer_win1_27793
27793
27811
870
TTTTAGCCTTTCTGCTATT
2073
AATAGCAGAAAGGCTAAAA

NC_045512.2_19mer_win1_27794
27794
27812
871
TTTAGCCTTTCTGCTATTC
2074
GAATAGCAGAAAGGCTAAA

NC_045512.2_19mer_win1_27795
27795
27813
872
TTAGCCTTTCTGCTATTCC
2075
GGAATAGCAGAAAGGCTAA

NC_045512.2_19mer_win1_27796
27796
27814
873
TAGCCTTTCTGCTATTCCT
2076
AGGAATAGCAGAAAGGCTA

NC_045512.2_19mer_win1_27797
27797
27815
874
AGCCTTTCTGCTATTCCTT
2077
AAGGAATAGCAGAAAGGCT

NC_045512.2_19mer_win1_27798
27798
27816
875
GCCTTTCTGCTATTCCTTG
2078
CAAGGAATAGCAGAAAGGC

NC_045512.2_19mer_win1_27799
27799
27817
876
CCTTTCTGCTATTCCTTGT
2079
ACAAGGAATAGCAGAAAGG

NC_045512.2_19mer_win1_27800
27800
27818
877
CTTTCTGCTATTCCTTGTT
2080
AACAAGGAATAGCAGAAAG

NC_045512.2_19mer_win1_28270
28270
28288
878
TAAAATGTCTGATAATGGA
2081
TCCATTATCAGACATTTTA

NC_045512.2_19mer_win1_28271
28271
28289
879
AAAATGTCTGATAATGGAC
2082
GTCCATTATCAGACATTTT

NC_045512.2_19mer_win1_28272
28272
28290
880
AAATGTCTGATAATGGACC
2083
GGTCCATTATCAGACATTT

NC_045512.2_19mer_win1_28273
28273
28291
881
AATGTCTGATAATGGACCC
2084
GGGTCCATTATCAGACATT

NC_045512.2_19mer_win1_28274
28274
28292
882
ATGTCTGATAATGGACCCC
2085
GGGGTCCATTATCAGACAT

NC_045512.2_19mer_win1_28275
28275
28293
883
TGTCTGATAATGGACCCCA
2086
TGGGGTCCATTATCAGACA

NC_045512.2_19mer_win1_28276
28276
28294
884
GTCTGATAATGGACCCCAA
2087
TTGGGGTCCATTATCAGAC

NC_045512.2_19mer_win1_28277
28277
28295
885
TCTGATAATGGACCCCAAA
2088
TTTGGGGTCCATTATCAGA

NC_045512.2_19mer_win1_28278
28278
28296
886
CTGATAATGGACCCCAAAA
2089
TTTTGGGGTCCATTATCAG

NC_045512.2_19mer_win1_28397
28397
28415
887
CCCCAAGGTTTACCCAATA
2090
TATTGGGTAAACCTTGGGG

NC_045512.2_19mer_win1_28398
28398
28416
888
CCCAAGGTTTACCCAATAA
2091
TTATTGGGTAAACCTTGGG

NC_045512.2_19mer_win1_28399
28399
28417
889
CCAAGGTTTACCCAATAAT
2092
ATTATTGGGTAAACCTTGG

NC_045512.2_19mer_win1_28400
28400
28418
890
CAAGGTTTACCCAATAATA
2093
TATTATTGGGTAAACCTTG

NC_045512.2_19mer_win1_28401
28401
28419
891
AAGGTTTACCCAATAATAC
2094
GTATTATTGGGTAAACCTT

NC_045512.2_19mer_win1_28402
28402
28420
892
AGGTTTACCCAATAATACT
2095
AGTATTATTGGGTAAACCT

NC_045512.2_19mer_win1_28403
28403
28421
893
GGTTTACCCAATAATACTG
2096
CAGTATTATTGGGTAAACC

NC_045512.2_19mer_win1_28404
28404
28422
894
GTTTACCCAATAATACTGC
2097
GCAGTATTATTGGGTAAAC

NC_045512.2_19mer_win1_28405
28405
28423
895
TTTACCCAATAATACTGCG
2098
CGCAGTATTATTGGGTAAA

NC_045512.2_19mer_win1_28406
28406
28424
896
TTACCCAATAATACTGCGT
2099
ACGCAGTATTATTGGGTAA

NC_045512.2_19mer_win1_28407
28407
28425
897
TACCCAATAATACTGCGTC
2100
GACGCAGTATTATTGGGTA

NC_045512.2_19mer_win1_28408
28408
28426
898
ACCCAATAATACTGCGTCT
2101
AGACGCAGTATTATTGGGT

NC_045512.2_19mer_win1_28409
28409
28427
899
CCCAATAATACTGCGTCTT
2102
AAGACGCAGTATTATTGGG

NC_045512.2_19mer_win1_28410
28410
28428
900
CCAATAATACTGCGTCTTG
2103
CAAGACGCAGTATTATTGG

NC_045512.2_19mer_win1_28411
28411
28429
901
CAATAATACTGCGTCTTGG
2104
CCAAGACGCAGTATTATTG

NC_045512.2_19mer_win1_28412
28412
28430
902
AATAATACTGCGTCTTGGT
2105
ACCAAGACGCAGTATTATT

NC_045512.2_19mer_win1_28413
28413
28431
903
ATAATACTGCGTCTTGGTT
2106
AACCAAGACGCAGTATTAT

NC_045512.2_19mer_win1_28414
28414
28432
904
TAATACTGCGTCTTGGTTC
2107
GAACCAAGACGCAGTATTA

NC_045512.2_19mer_win1_28415
28415
28433
905
AATACTGCGTCTTGGTTCA
2108
TGAACCAAGACGCAGTATT

NC_045512.2_19mer_win1_28416
28416
28434
906
ATACTGCGTCTTGGTTCAC
2109
GTGAACCAAGACGCAGTAT

NC_045512.2_19mer_win1_28513
28513
28531
907
AGATGACCAAATTGGCTAC
2110
GTAGCCAATTTGGTCATCT

NC_045512.2_19mer_win1_28514
28514
28532
908
GATGACCAAATTGGCTACT
2111
AGTAGCCAATTTGGTCATC

NC_045512.2_19mer_win1_28515
28515
28533
909
ATGACCAAATTGGCTACTA
2112
TAGTAGCCAATTTGGTCAT

NC_045512.2_19mer_win1_28516
28516
28534
910
TGACCAAATTGGCTACTAC
2113
GTAGTAGCCAATTTGGTCA

NC_045512.2_19mer_win1_28517
28517
28535
911
GACCAAATTGGCTACTACC
2114
GGTAGTAGCCAATTTGGTC

NC_045512.2_19mer_win1_28518
28518
28536
912
ACCAAATTGGCTACTACCG
2115
CGGTAGTAGCCAATTTGGT

NC_045512.2_19mer_win1_28519
28519
28537
913
CCAAATTGGCTACTACCGA
2116
TCGGTAGTAGCCAATTTGG

NC_045512.2_19mer_win1_28520
28520
28538
914
CAAATTGGCTACTACCGAA
2117
TTCGGTAGTAGCCAATTTG

NC_045512.2_19mer_win1_28521
28521
28539
915
AAATTGGCTACTACCGAAG
2118
CTTCGGTAGTAGCCAATTT

NC_045512.2_19mer_win1_28522
28522
28540
916
AATTGGCTACTACCGAAGA
2119
TCTTCGGTAGTAGCCAATT

NC_045512.2_19mer_win1_28523
28523
28541
917
ATTGGCTACTACCGAAGAG
2120
CTCTTCGGTAGTAGCCAAT

NC_045512.2_19mer_win1_28524
28524
28542
918
TTGGCTACTACCGAAGAGC
2121
GCTCTTCGGTAGTAGCCAA

NC_045512.2_19mer_win1_28525
28525
28543
919
TGGCTACTACCGAAGAGCT
2122
AGCTCTTCGGTAGTAGCCA

NC_045512.2_19mer_win1_28526
28526
28544
920
GGCTACTACCGAAGAGCTA
2123
TAGCTCTTCGGTAGTAGCC

NC_045512.2_19mer_win1_28527
28527
28545
921
GCTACTACCGAAGAGCTAC
2124
GTAGCTCTTCGGTAGTAGC

NC_045512.2_19mer_win1_28528
28528
28546
922
CTACTACCGAAGAGCTACC
2125
GGTAGCTCTTCGGTAGTAG

NC_045512.2_19mer_win1_28673
28673
28691
923
GCAACTGAGGGAGCCTTGA
2126
TCAAGGCTCCCTCAGTTGC

NC_045512.2_19mer_win1_28674
28674
28692
924
CAACTGAGGGAGCCTTGAA
2127
TTCAAGGCTCCCTCAGTTG

NC_045512.2_19mer_win1_28706
28706
28724
925
CACATTGGCACCCGCAATC
2128
GATTGCGGGTGCCAATGTG

NC_045512.2_19mer_win1_28707
28707
28725
926
ACATTGGCACCCGCAATCC
2129
GGATTGCGGGTGCCAATGT

NC_045512.2_19mer_win1_28708
28708
28726
927
CATTGGCACCCGCAATCCT
2130
AGGATTGCGGGTGCCAATG

NC_045512.2_19mer_win1_28744
28744
28762
928
CGTGCTACAACTTCCTCAA
2131
TTGAGGAAGTTGTAGCACG

NC_045512.2_19mer_win1_28745
28745
28763
929
GTGCTACAACTTCCTCAAG
2132
CTTGAGGAAGTTGTAGCAC

NC_045512.2_19mer_win1_28746
28746
28764
930
TGCTACAACTTCCTCAAGG
2133
CCTTGAGGAAGTTGTAGCA

NC_045512.2_19mer_win1_28747
28747
28765
931
GCTACAACTTCCTCAAGGA
2134
TCCTTGAGGAAGTTGTAGC

NC_045512.2_19mer_win1_28748
28748
28766
932
CTACAACTTCCTCAAGGAA
2135
TTCCTTGAGGAAGTTGTAG

NC_045512.2_19mer_win1_28749
28749
28767
933
TACAACTTCCTCAAGGAAC
2136
GTTCCTTGAGGAAGTTGTA

NC_045512.2_19mer_win1_28750
28750
28768
934
ACAACTTCCTCAAGGAACA
2137
TGTTCCTTGAGGAAGTTGT

NC_045512.2_19mer_win1_28751
28751
28769
935
CAACTTCCTCAAGGAACAA
2138
TTGTTCCTTGAGGAAGTTG

NC_045512.2_19mer_win1_28752
28752
28770
936
AACTTCCTCAAGGAACAAC
2139
GTTGTTCCTTGAGGAAGTT

NC_045512.2_19mer_win1_28753
28753
28771
937
ACTTCCTCAAGGAACAACA
2140
TGTTGTTCCTTGAGGAAGT

NC_045512.2_19mer_win1_28754
28754
28772
938
CTTCCTCAAGGAACAACAT
2141
ATGTTGTTCCTTGAGGAAG

NC_045512.2_19mer_win1_28755
28755
28773
939
TTCCTCAAGGAACAACATT
2142
AATGTTGTTCCTTGAGGAA

NC_045512.2_19mer_win1_28756
28756
28774
940
TCCTCAAGGAACAACATTG
2143
CAATGTTGTTCCTTGAGGA

NC_045512.2_19mer_win1_28757
28757
28775
941
CCTCAAGGAACAACATTGC
2144
GCAATGTTGTTCCTTGAGG

NC_045512.2_19mer_win1_28758
28758
28776
942
CTCAAGGAACAACATTGCC
2145
GGCAATGTTGTTCCTTGAG

NC_045512.2_19mer_win1_28759
28759
28777
943
TCAAGGAACAACATTGCCA
2146
TGGCAATGTTGTTCCTTGA

NC_045512.2_19mer_win1_28760
28760
28778
944
CAAGGAACAACATTGCCAA
2147
TTGGCAATGTTGTTCCTTG

NC_045512.2_19mer_win1_28761
28761
28779
945
AAGGAACAACATTGCCAAA
2148
TTTGGCAATGTTGTTCCTT

NC_045512.2_19mer_win1_28762
28762
28780
946
AGGAACAACATTGCCAAAA
2149
TTTTGGCAATGTTGTTCCT

NC_045512.2_19mer_win1_28763
28763
28781
947
GGAACAACATTGCCAAAAG
2150
CTTTTGGCAATGTTGTTCC

NC_045512.2_19mer_win1_28764
28764
28782
948
GAACAACATTGCCAAAAGG
2151
CCTTTTGGCAATGTTGTTC

NC_045512.2_19mer_win1_28765
28765
28783
949
AACAACATTGCCAAAAGGC
2152
GCCTTTTGGCAATGTTGTT

NC_045512.2_19mer_win1_28766
28766
28784
950
ACAACATTGCCAAAAGGCT
2153
AGCCTTTTGGCAATGTTGT

NC_045512.2_19mer_win1_28767
28767
28785
951
CAACATTGCCAAAAGGCTT
2154
AAGCCTTTTGGCAATGTTG

NC_045512.2_19mer_win1_28768
28768
28786
952
AACATTGCCAAAAGGCTTC
2155
GAAGCCTTTTGGCAATGTT

NC_045512.2_19mer_win1_28769
28769
28787
953
ACATTGCCAAAAGGCTTCT
2156
AGAAGCCTTTTGGCAATGT

NC_045512.2_19mer_win1_28770
28770
28788
954
CATTGCCAAAAGGCTTCTA
2157
TAGAAGCCTTTTGGCAATG

NC_045512.2_19mer_win1_28771
28771
28789
955
ATTGCCAAAAGGCTTCTAC
2158
GTAGAAGCCTTTTGGCAAT

NC_045512.2_19mer_win1_28772
28772
28790
956
TTGCCAAAAGGCTTCTACG
2159
CGTAGAAGCCTTTTGGCAA

NC_045512.2_19mer_win1_28773
28773
28791
957
TGCCAAAAGGCTTCTACGC
2160
GCGTAGAAGCCTTTTGGCA

NC_045512.2_19mer_win1_28774
28774
28792
958
GCCAAAAGGCTTCTACGCA
2161
TGCGTAGAAGCCTTTTGGC

NC_045512.2_19mer_win1_28775
28775
28793
959
CCAAAAGGCTTCTACGCAG
2162
CTGCGTAGAAGCCTTTTGG

NC_045512.2_19mer_win1_28776
28776
28794
960
CAAAAGGCTTCTACGCAGA
2163
TCTGCGTAGAAGCCTTTTG

NC_045512.2_19mer_win1_28799
28799
28817
961
AGCAGAGGCGGCAGTCAAG
2164
CTTGACTGCCGCCTCTGCT

NC_045512.2_19mer_win1_28800
28800
28818
962
GCAGAGGCGGCAGTCAAGC
2165
GCTTGACTGCCGCCTCTGC

NC_045512.2_19mer_win1_28801
28801
28819
963
CAGAGGCGGCAGTCAAGCC
2166
GGCTTGACTGCCGCCTCTG

NC_045512.2_19mer_win1_28802
28802
28820
964
AGAGGCGGCAGTCAAGCCT
2167
AGGCTTGACTGCCGCCTCT

NC_045512.2_19mer_win1_28803
28803
28821
965
GAGGCGGCAGTCAAGCCTC
2168
GAGGCTTGACTGCCGCCTC

NC_045512.2_19mer_win1_28804
28804
28822
966
AGGCGGCAGTCAAGCCTCT
2169
AGAGGCTTGACTGCCGCCT

NC_045512.2_19mer_win1_28805
28805
28823
967
GGCGGCAGTCAAGCCTCTT
2170
AAGAGGCTTGACTGCCGCC

NC_045512.2_19mer_win1_28806
28806
28824
968
GCGGCAGTCAAGCCTCTTC
2171
GAAGAGGCTTGACTGCCGC

NC_045512.2_19mer_win1_28807
28807
28825
969
CGGCAGTCAAGCCTCTTCT
2172
AGAAGAGGCTTGACTGCCG

NC_045512.2_19mer_win1_28808
28808
28826
970
GGCAGTCAAGCCTCTTCTC
2173
GAGAAGAGGCTTGACTGCC

NC_045512.2_19mer_win1_28809
28809
28827
971
GCAGTCAAGCCTCTTCTCG
2174
CGAGAAGAGGCTTGACTGC

NC_045512.2_19mer_win1_28946
28946
28964
972
GACAGATTGAACCAGCTTG
2175
CAAGCTGGTTCAATCTGTC

NC_045512.2_19mer_win1_28947
28947
28965
973
ACAGATTGAACCAGCTTGA
2176
TCAAGCTGGTTCAATCTGT

NC_045512.2_19mer_win1_28948
28948
28966
974
CAGATTGAACCAGCTTGAG
2177
CTCAAGCTGGTTCAATCTG

NC_045512.2_19mer_win1_28949
28949
28967
975
AGATTGAACCAGCTTGAGA
2178
TCTCAAGCTGGTTCAATCT

NC_045512.2_19mer_win1_28950
28950
28968
976
GATTGAACCAGCTTGAGAG
2179
CTCTCAAGCTGGTTCAATC

NC_045512.2_19mer_win1_28951
28951
28969
977
ATTGAACCAGCTTGAGAGC
2180
GCTCTCAAGCTGGTTCAAT

NC_045512.2_19mer_win1_28952
28952
28970
978
TTGAACCAGCTTGAGAGCA
2181
TGCTCTCAAGCTGGTTCAA

NC_045512.2_19mer_win1_28953
28953
28971
979
TGAACCAGCTTGAGAGCAA
2182
TTGCTCTCAAGCTGGTTCA

NC_045512.2_19mer_win1_28954
28954
28972
980
GAACCAGCTTGAGAGCAAA
2183
TTTGCTCTCAAGCTGGTTC

NC_045512.2_19mer_win1_28976
28976
28994
981
TCTGGTAAAGGCCAACAAC
2184
GTTGTTGGCCTTTACCAGA

NC_045512.2_19mer_win1_28977
28977
28995
982
CTGGTAAAGGCCAACAACA
2185
TGTTGTTGGCCTTTACCAG

NC_045512.2_19mer_win1_28978
28978
28996
983
TGGTAAAGGCCAACAACAA
2186
TTGTTGTTGGCCTTTACCA

NC_045512.2_19mer_win1_28979
28979
28997
984
GGTAAAGGCCAACAACAAC
2187
GTTGTTGTTGGCCTTTACC

NC_045512.2_19mer_win1_28980
28980
28998
985
GTAAAGGCCAACAACAACA
2188
TGTTGTTGTTGGCCTTTAC

NC_045512.2_19mer_win1_28981
28981
28999
986
TAAAGGCCAACAACAACAA
2189
TTGTTGTTGTTGGCCTTTA

NC_045512.2_19mer_win1_28982
28982
29000
987
AAAGGCCAACAACAACAAG
2190
CTTGTTGTTGTTGGCCTTT

NC_045512.2_19mer_win1_28983
28983
29001
988
AAGGCCAACAACAACAAGG
2191
CCTTGTTGTTGTTGGCCTT

NC_045512.2_19mer_win1_28984
28984
29002
989
AGGCCAACAACAACAAGGC
2192
GCCTTGTTGTTGTTGGCCT

NC_045512.2_19mer_win1_28985
28985
29003
990
GGCCAACAACAACAAGGCC
2193
GGCCTTGTTGTTGTTGGCC

NC_045512.2_19mer_win1_28986
28986
29004
991
GCCAACAACAACAAGGCCA
2194
TGGCCTTGTTGTTGTTGGC

NC_045512.2_19mer_win1_28987
28987
29005
992
CCAACAACAACAAGGCCAA
2195
TTGGCCTTGTTGTTGTTGG

NC_045512.2_19mer_win1_28988
28988
29006
993
CAACAACAACAAGGCCAAA
2196
TTTGGCCTTGTTGTTGTTG

NC_045512.2_19mer_win1_28989
28989
29007
994
AACAACAACAAGGCCAAAC
2197
GTTTGGCCTTGTTGTTGTT

NC_045512.2_19mer_win1_28990
28990
29008
995
ACAACAACAAGGCCAAACT
2198
AGTTTGGCCTTGTTGTTGT

NC_045512.2_19mer_win1_28991
28991
29009
996
CAACAACAAGGCCAAACTG
2199
CAGTTTGGCCTTGTTGTTG

NC_045512.2_19mer_win1_28992
28992
29010
997
AACAACAAGGCCAAACTGT
2200
ACAGTTTGGCCTTGTTGTT

NC_045512.2_19mer_win1_28993
28993
29011
998
ACAACAAGGCCAAACTGTC
2201
GACAGTTTGGCCTTGTTGT

NC_045512.2_19mer_win1_28994
28994
29012
999
CAACAAGGCCAAACTGTCA
2202
TGACAGTTTGGCCTTGTTG

NC_045512.2_19mer_win1_28995
28995
29013
1000
AACAAGGCCAAACTGTCAC
2203
GTGACAGTTTGGCCTTGTT

NC_045512.2_19mer_win1_28996
28996
29014
1001
ACAAGGCCAAACTGTCACT
2204
AGTGACAGTTTGGCCTTGT

NC_045512.2_19mer_win1_28997
28997
29015
1002
CAAGGCCAAACTGTCACTA
2205
TAGTGACAGTTTGGCCTTG

NC_045512.2_19mer_win1_28998
28998
29016
1003
AAGGCCAAACTGTCACTAA
2206
TTAGTGACAGTTTGGCCTT

NC_045512.2_19mer_win1_28999
28999
29017
1004
AGGCCAAACTGTCACTAAG
2207
CTTAGTGACAGTTTGGCCT

NC_045512.2_19mer_win1_29000
29000
29018
1005
GGCCAAACTGTCACTAAGA
2208
TCTTAGTGACAGTTTGGCC

NC_045512.2_19mer_win1_29001
29001
29019
1006
GCCAAACTGTCACTAAGAA
2209
TTCTTAGTGACAGTTTGGC

NC_045512.2_19mer_win1_29002
29002
29020
1007
CCAAACTGTCACTAAGAAA
2210
TTTCTTAGTGACAGTTTGG

NC_045512.2_19mer_win1_29003
29003
29021
1008
CAAACTGTCACTAAGAAAT
2211
ATTTCTTAGTGACAGTTTG

NC_045512.2_19mer_win1_29004
29004
29022
1009
AAACTGTCACTAAGAAATC
2212
GATTTCTTAGTGACAGTTT

NC_045512.2_19mer_win1_29005
29005
29023
1010
AACTGTCACTAAGAAATCT
2213
AGATTTCTTAGTGACAGTT

NC_045512.2_19mer_win1_29006
29006
29024
1011
ACTGTCACTAAGAAATCTG
2214
CAGATTTCTTAGTGACAGT

NC_045512.2_19mer_win1_29007
29007
29025
1012
CTGTCACTAAGAAATCTGC
2215
GCAGATTTCTTAGTGACAG

NC_045512.2_19mer_win1_29008
29008
29026
1013
TGTCACTAAGAAATCTGCT
2216
AGCAGATTTCTTAGTGACA

NC_045512.2_19mer_win1_29009
29009
29027
1014
GTCACTAAGAAATCTGCTG
2217
CAGCAGATTTCTTAGTGAC

NC_045512.2_19mer_win1_29010
29010
29028
1015
TCACTAAGAAATCTGCTGC
2218
GCAGCAGATTTCTTAGTGA

NC_045512.2_19mer_win1_29011
29011
29029
1016
CACTAAGAAATCTGCTGCT
2219
AGCAGCAGATTTCTTAGTG

NC_045512.2_19mer_win1_29012
29012
29030
1017
ACTAAGAAATCTGCTGCTG
2220
CAGCAGCAGATTTCTTAGT

NC_045512.2_19mer_win1_29013
29013
29031
1018
CTAAGAAATCTGCTGCTGA
2221
TCAGCAGCAGATTTCTTAG

NC_045512.2_19mer_win1_29014
29014
29032
1019
TAAGAAATCTGCTGCTGAG
2222
CTCAGCAGCAGATTTCTTA

NC_045512.2_19mer_win1_29015
29015
29033
1020
AAGAAATCTGCTGCTGAGG
2223
CCTCAGCAGCAGATTTCTT

NC_045512.2_19mer_win1_29016
29016
29034
1021
AGAAATCTGCTGCTGAGGC
2224
GCCTCAGCAGCAGATTTCT

NC_045512.2_19mer_win1_29144
29144
29162
1022
CTAATCAGACAAGGAACTG
2225
CAGTTCCTTGTCTGATTAG

NC_045512.2_19mer_win1_29145
29145
29163
1023
TAATCAGACAAGGAACTGA
2226
TCAGTTCCTTGTCTGATTA

NC_045512.2_19mer_win1_29146
29146
29164
1024
AATCAGACAAGGAACTGAT
2227
ATCAGTTCCTTGTCTGATT

NC_045512.2_19mer_win1_29147
29147
29165
1025
ATCAGACAAGGAACTGATT
2228
AATCAGTTCCTTGTCTGAT

NC_045512.2_19mer_win1_29148
29148
29166
1026
TCAGACAAGGAACTGATTA
2229
TAATCAGTTCCTTGTCTGA

NC_045512.2_19mer_win1_29149
29149
29167
1027
CAGACAAGGAACTGATTAC
2230
GTAATCAGTTCCTTGTCTG

NC_045512.2_19mer_win1_29150
29150
29168
1028
AGACAAGGAACTGATTACA
2231
TGTAATCAGTTCCTTGTCT

NC_045512.2_19mer_win1_29151
29151
29169
1029
GACAAGGAACTGATTACAA
2232
TTGTAATCAGTTCCTTGTC

NC_045512.2_19mer_win1_29152
29152
29170
1030
ACAAGGAACTGATTACAAA
2233
TTTGTAATCAGTTCCTTGT

NC_045512.2_19mer_win1_29153
29153
29171
1031
CAAGGAACTGATTACAAAC
2234
GTTTGTAATCAGTTCCTTG

NC_045512.2_19mer_win1_29154
29154
29172
1032
AAGGAACTGATTACAAACA
2235
TGTTTGTAATCAGTTCCTT

NC_045512.2_19mer_win1_29174
29174
29192
1033
TGGCCGCAAATTGCACAAT
2236
ATTGTGCAATTTGCGGCCA

NC_045512.2_19mer_win1_29175
29175
29193
1034
GGCCGCAAATTGCACAATT
2237
AATTGTGCAATTTGCGGCC

NC_045512.2_19mer_win1_29176
29176
29194
1035
GCCGCAAATTGCACAATTT
2238
AAATTGTGCAATTTGCGGC

NC_045512.2_19mer_win1_29177
29177
29195
1036
CCGCAAATTGCACAATTTG
2239
CAAATTGTGCAATTTGCGG

NC_045512.2_19mer_win1_29178
29178
29196
1037
CGCAAATTGCACAATTTGC
2240
GCAAATTGTGCAATTTGCG

NC_045512.2_19mer_win1_29228
29228
29246
1038
CGCATTGGCATGGAAGTCA
2241
TGACTTCCATGCCAATGCG

NC_045512.2_19mer_win1_29229
29229
29247
1039
GCATTGGCATGGAAGTCAC
2242
GTGACTTCCATGCCAATGC

NC_045512.2_19mer_win1_29230
29230
29248
1040
CATTGGCATGGAAGTCACA
2243
TGTGACTTCCATGCCAATG

NC_045512.2_19mer_win1_29231
29231
29249
1041
ATTGGCATGGAAGTCACAC
2244
GTGTGACTTCCATGCCAAT

NC_045512.2_19mer_win1_29232
29232
29250
1042
TTGGCATGGAAGTCACACC
2245
GGTGTGACTTCCATGCCAA

NC_045512.2_19mer_win1_29233
29233
29251
1043
TGGCATGGAAGTCACACCT
2246
AGGTGTGACTTCCATGCCA

NC_045512.2_19mer_win1_29234
29234
29252
1044
GGCATGGAAGTCACACCTT
2247
AAGGTGTGACTTCCATGCC

NC_045512.2_19mer_win1_29235
29235
29253
1045
GCATGGAAGTCACACCTTC
2248
GAAGGTGTGACTTCCATGC

NC_045512.2_19mer_win1_29236
29236
29254
1046
CATGGAAGTCACACCTTCG
2249
CGAAGGTGTGACTTCCATG

NC_045512.2_19mer_win1_29237
29237
29255
1047
ATGGAAGTCACACCTTCGG
2250
CCGAAGGTGTGACTTCCAT

NC_045512.2_19mer_win1_29238
29238
29256
1048
TGGAAGTCACACCTTCGGG
2251
CCCGAAGGTGTGACTTCCA

NC_045512.2_19mer_win1_29239
29239
29257
1049
GGAAGTCACACCTTCGGGA
2252
TCCCGAAGGTGTGACTTCC

NC_045512.2_19mer_win1_29240
29240
29258
1050
GAAGTCACACCTTCGGGAA
2253
TTCCCGAAGGTGTGACTTC

NC_045512.2_19mer_win1_29241
29241
29259
1051
AAGTCACACCTTCGGGAAC
2254
GTTCCCGAAGGTGTGACTT

NC_045512.2_19mer_win1_29285
29285
29303
1052
AAATTGGATGACAAAGATC
2255
GATCTTTGTCATCCAATTT

NC_045512.2_19mer_win1_29286
29286
29304
1053
AATTGGATGACAAAGATCC
2256
GGATCTTTGTCATCCAATT

NC_045512.2_19mer_win1_29287
29287
29305
1054
ATTGGATGACAAAGATCCA
2257
TGGATCTTTGTCATCCAAT

NC_045512.2_19mer_win1_29342
29342
29360
1055
ATTGACGCATACAAAACAT
2258
ATGTTTTGTATGCGTCAAT

NC_045512.2_19mer_win1_29343
29343
29361
1056
TTGACGCATACAAAACATT
2259
AATGTTTTGTATGCGTCAA

NC_045512.2_19mer_win1_29344
29344
29362
1057
TGACGCATACAAAACATTC
2260
GAATGTTTTGTATGCGTCA

NC_045512.2_19mer_win1_29345
29345
29363
1058
GACGCATACAAAACATTCC
2261
GGAATGTTTTGTATGCGTC

NC_045512.2_19mer_win1_29346
29346
29364
1059
ACGCATACAAAACATTCCC
2262
GGGAATGTTTTGTATGCGT

NC_045512.2_19mer_win1_29347
29347
29365
1060
CGCATACAAAACATTCCCA
2263
TGGGAATGTTTTGTATGCG

NC_045512.2_19mer_win1_29348
29348
29366
1061
GCATACAAAACATTCCCAC
2264
GTGGGAATGTTTTGTATGC

NC_045512.2_19mer_win1_29349
29349
29367
1062
CATACAAAACATTCCCACC
2265
GGTGGGAATGTTTTGTATG

NC_045512.2_19mer_win1_29350
29350
29368
1063
ATACAAAACATTCCCACCA
2266
TGGTGGGAATGTTTTGTAT

NC_045512.2_19mer_win1_29351
29351
29369
1064
TACAAAACATTCCCACCAA
2267
TTGGTGGGAATGTTTTGTA

NC_045512.2_19mer_win1_29352
29352
29370
1065
ACAAAACATTCCCACCAAC
2268
GTTGGTGGGAATGTTTTGT

NC_045512.2_19mer_win1_29353
29353
29371
1066
CAAAACATTCCCACCAACA
2269
TGTTGGTGGGAATGTTTTG

NC_045512.2_19mer_win1_29354
29354
29372
1067
AAAACATTCCCACCAACAG
2270
CTGTTGGTGGGAATGTTTT

NC_045512.2_19mer_win1_29355
29355
29373
1068
AAACATTCCCACCAACAGA
2271
TCTGTTGGTGGGAATGTTT

NC_045512.2_19mer_win1_29356
29356
29374
1069
AACATTCCCACCAACAGAG
2272
CTCTGTTGGTGGGAATGTT

NC_045512.2_19mer_win1_29357
29357
29375
1070
ACATTCCCACCAACAGAGC
2273
GCTCTGTTGGTGGGAATGT

NC_045512.2_19mer_win1_29358
29358
29376
1071
CATTCCCACCAACAGAGCC
2274
GGCTCTGTTGGTGGGAATG

NC_045512.2_19mer_win1_29359
29359
29377
1072
ATTCCCACCAACAGAGCCT
2275
AGGCTCTGTTGGTGGGAAT

NC_045512.2_19mer_win1_29360
29360
29378
1073
TTCCCACCAACAGAGCCTA
2276
TAGGCTCTGTTGGTGGGAA

NC_045512.2_19mer_win1_29361
29361
29379
1074
TCCCACCAACAGAGCCTAA
2277
TTAGGCTCTGTTGGTGGGA

NC_045512.2_19mer_win1_29362
29362
29380
1075
CCCACCAACAGAGCCTAAA
2278
TTTAGGCTCTGTTGGTGGG

NC_045512.2_19mer_win1_29363
29363
29381
1076
CCACCAACAGAGCCTAAAA
2279
TTTTAGGCTCTGTTGGTGG

NC_045512.2_19mer_win1_29364
29364
29382
1077
CACCAACAGAGCCTAAAAA
2280
TTTTTAGGCTCTGTTGGTG

NC_045512.2_19mer_win1_29365
29365
29383
1078
ACCAACAGAGCCTAAAAAG
2281
CTTTTTAGGCTCTGTTGGT

NC_045512.2_19mer_win1_29366
29366
29384
1079
CCAACAGAGCCTAAAAAGG
2282
CCTTTTTAGGCTCTGTTGG

NC_045512.2_19mer_win1_29367
29367
29385
1080
CAACAGAGCCTAAAAAGGA
2283
TCCTTTTTAGGCTCTGTTG

NC_045512.2_19mer_win1_29368
29368
29386
1081
AACAGAGCCTAAAAAGGAC
2284
GTCCTTTTTAGGCTCTGTT

NC_045512.2_19mer_win1_29369
29369
29387
1082
ACAGAGCCTAAAAAGGACA
2285
TGTCCTTTTTAGGCTCTGT

NC_045512.2_19mer_win1_29370
29370
29388
1083
CAGAGCCTAAAAAGGACAA
2286
TTGTCCTTTTTAGGCTCTG

NC_045512.2_19mer_win1_29371
29371
29389
1084
AGAGCCTAAAAAGGACAAA
2287
TTTGTCCTTTTTAGGCTCT

NC_045512.2_19mer_win1_29372
29372
29390
1085
GAGCCTAAAAAGGACAAAA
2288
TTTTGTCCTTTTTAGGCTC

NC_045512.2_19mer_win1_29373
29373
29391
1086
AGCCTAAAAAGGACAAAAA
2289
TTTTTGTCCTTTTTAGGCT

NC_045512.2_19mer_win1_29374
29374
29392
1087
GCCTAAAAAGGACAAAAAG
2290
CTTTTTGTCCTTTTTAGGC

NC_045512.2_19mer_win1_29375
29375
29393
1088
CCTAAAAAGGACAAAAAGA
2291
TCTTTTTGTCCTTTTTAGG

NC_045512.2_19mer_win1_29376
29376
29394
1089
CTAAAAAGGACAAAAAGAA
2292
TTCTTTTTGTCCTTTTTAG

NC_045512.2_19mer_win1_29444
29444
29462
1090
ACTGTGACTCTTCTTCCTG
2293
CAGGAAGAAGAGTCACAGT

NC_045512.2_19mer_win1_29445
29445
29463
1091
CTGTGACTCTTCTTCCTGC
2294
GCAGGAAGAAGAGTCACAG

NC_045512.2_19mer_win1_29543
29543
29561
1092
GACCACACAAGGCAGATGG
2295
CCATCTGCCTTGTGTGGTC

NC_045512.2_19mer_win1_29544
29544
29562
1093
ACCACACAAGGCAGATGGG
2296
CCCATCTGCCTTGTGTGGT

NC_045512.2_19mer_win1_29545
29545
29563
1094
CCACACAAGGCAGATGGGC
2297
GCCCATCTGCCTTGTGTGG

NC_045512.2_19mer_win1_29546
29546
29564
1095
CACACAAGGCAGATGGGCT
2298
AGCCCATCTGCCTTGTGTG

NC_045512.2_19mer_win1_29547
29547
29565
1096
ACACAAGGCAGATGGGCTA
2299
TAGCCCATCTGCCTTGTGT

NC_045512.2_19mer_win1_29548
29548
29566
1097
CACAAGGCAGATGGGCTAT
2300
ATAGCCCATCTGCCTTGTG

NC_045512.2_19mer_win1_29598
29598
29616
1098
ATAGTCTACTCTTGTGCAG
2301
CTGCACAAGAGTAGACTAT

NC_045512.2_19mer_win1_29599
29599
29617
1099
TAGTCTACTCTTGTGCAGA
2302
TCTGCACAAGAGTAGACTA

NC_045512.2_19mer_win1_29600
29600
29618
1100
AGTCTACTCTTGTGCAGAA
2303
TTCTGCACAAGAGTAGACT

NC_045512.2_19mer_win1_29601
29601
29619
1101
GTCTACTCTTGTGCAGAAT
2304
ATTCTGCACAAGAGTAGAC

NC_045512.2_19mer_win1_29602
29602
29620
1102
TCTACTCTTGTGCAGAATG
2305
CATTCTGCACAAGAGTAGA

NC_045512.2_19mer_win1_29603
29603
29621
1103
CTACTCTTGTGCAGAATGA
2306
TCATTCTGCACAAGAGTAG

NC_045512.2_19mer_win1_29604
29604
29622
1104
TACTCTTGTGCAGAATGAA
2307
TTCATTCTGCACAAGAGTA

NC_045512.2_19mer_win1_29605
29605
29623
1105
ACTCTTGTGCAGAATGAAT
2308
ATTCATTCTGCACAAGAGT

NC_045512.2_19mer_win1_29606
29606
29624
1106
CTCTTGTGCAGAATGAATT
2309
AATTCATTCTGCACAAGAG

NC_045512.2_19mer_win1_29607
29607
29625
1107
TCTTGTGCAGAATGAATTC
2310
GAATTCATTCTGCACAAGA

NC_045512.2_19mer_win1_29608
29608
29626
1108
CTTGTGCAGAATGAATTCT
2311
AGAATTCATTCTGCACAAG

NC_045512.2_19mer_win1_29609
29609
29627
1109
TTGTGCAGAATGAATTCTC
2312
GAGAATTCATTCTGCACAA

NC_045512.2_19mer_win1_29610
29610
29628
1110
TGTGCAGAATGAATTCTCG
2313
CGAGAATTCATTCTGCACA

NC_045512.2_19mer_win1_29611
29611
29629
1111
GTGCAGAATGAATTCTCGT
2314
ACGAGAATTCATTCTGCAC

NC_045512.2_19mer_win1_29612
29612
29630
1112
TGCAGAATGAATTCTCGTA
2315
TACGAGAATTCATTCTGCA

NC_045512.2_19mer_win1_29652
29652
29670
1113
TAGTTAACTTTAATCTCAC
2316
GTGAGATTAAAGTTAACTA

NC_045512.2_19mer_win1_29653
29653
29671
1114
AGTTAACTTTAATCTCACA
2317
TGTGAGATTAAAGTTAACT

NC_045512.2_19mer_win1_29654
29654
29672
1115
GTTAACTTTAATCTCACAT
2318
ATGTGAGATTAAAGTTAAC

NC_045512.2_19mer_win1_29655
29655
29673
1116
TTAACTTTAATCTCACATA
2319
TATGTGAGATTAAAGTTAA

NC_045512.2_19mer_win1_29656
29656
29674
1117
TAACTTTAATCTCACATAG
2320
CTATGTGAGATTAAAGTTA

NC_045512.2_19mer_win1_29657
29657
29675
1118
AACTTTAATCTCACATAGC
2321
GCTATGTGAGATTAAAGTT

NC_045512.2_19mer_win1_29658
29658
29676
1119
ACTTTAATCTCACATAGCA
2322
TGCTATGTGAGATTAAAGT

NC_045512.2_19mer_win1_29659
29659
29677
1120
CTTTAATCTCACATAGCAA
2323
TTGCTATGTGAGATTAAAG

NC_045512.2_19mer_win1_29660
29660
29678
1121
TTTAATCTCACATAGCAAT
2324
ATTGCTATGTGAGATTAAA

NC_045512.2_19mer_win1_29661
29661
29679
1122
TTAATCTCACATAGCAATC
2325
GATTGCTATGTGAGATTAA

NC_045512.2_19mer_win1_29662
29662
29680
1123
TAATCTCACATAGCAATCT
2326
AGATTGCTATGTGAGATTA

NC_045512.2_19mer_win1_29663
29663
29681
1124
AATCTCACATAGCAATCTT
2327
AAGATTGCTATGTGAGATT

NC_045512.2_19mer_win1_29664
29664
29682
1125
ATCTCACATAGCAATCTTT
2328
AAAGATTGCTATGTGAGAT

NC_045512.2_19mer_win1_29665
29665
29683
1126
TCTCACATAGCAATCTTTA
2329
TAAAGATTGCTATGTGAGA

NC_045512.2_19mer_win1_29666
29666
29684
1127
CTCACATAGCAATCTTTAA
2330
TTAAAGATTGCTATGTGAG

NC_045512.2_19mer_win1_29667
29667
29685
1128
TCACATAGCAATCTTTAAT
2331
ATTAAAGATTGCTATGTGA

NC_045512.2_19mer_win1_29668
29668
29686
1129
CACATAGCAATCTTTAATC
2332
GATTAAAGATTGCTATGTG

NC_045512.2_19mer_win1_29669
29669
29687
1130
ACATAGCAATCTTTAATCA
2333
TGATTAAAGATTGCTATGT

NC_045512.2_19mer_win1_29689
29689
29707
1131
TGTGTAACATTAGGGAGGA
2334
TCCTCCCTAATGTTACACA

NC_045512.2_19mer_win1_29690
29690
29708
1132
GTGTAACATTAGGGAGGAC
2335
GTCCTCCCTAATGTTACAC

NC_045512.2_19mer_win1_29691
29691
29709
1133
TGTAACATTAGGGAGGACT
2336
AGTCCTCCCTAATGTTACA

NC_045512.2_19mer_win1_29692
29692
29710
1134
GTAACATTAGGGAGGACTT
2337
AAGTCCTCCCTAATGTTAC

NC_045512.2_19mer_win1_29693
29693
29711
1135
TAACATTAGGGAGGACTTG
2338
CAAGTCCTCCCTAATGTTA

NC_045512.2_19mer_win1_29694
29694
29712
1136
AACATTAGGGAGGACTTGA
2339
TCAAGTCCTCCCTAATGTT

NC_045512.2_19mer_win1_29695
29695
29713
1137
ACATTAGGGAGGACTTGAA
2340
TTCAAGTCCTCCCTAATGT

NC_045512.2_19mer_win1_29696
29696
29714
1138
CATTAGGGAGGACTTGAAA
2341
TTTCAAGTCCTCCCTAATG

NC_045512.2_19mer_win1_29697
29697
29715
1139
ATTAGGGAGGACTTGAAAG
2342
CTTTCAAGTCCTCCCTAAT

NC_045512.2_19mer_win1_29698
29698
29716
1140
TTAGGGAGGACTTGAAAGA
2343
TCTTTCAAGTCCTCCCTAA

NC_045512.2_19mer_win1_29699
29699
29717
1141
TAGGGAGGACTTGAAAGAG
2344
CTCTTTCAAGTCCTCCCTA

NC_045512.2_19mer_win1_29700
29700
29718
1142
AGGGAGGACTTGAAAGAGC
2345
GCTCTTTCAAGTCCTCCCT

NC_045512.2_19mer_win1_29701
29701
29719
1143
GGGAGGACTTGAAAGAGCC
2346
GGCTCTTTCAAGTCCTCCC

NC_045512.2_19mer_win1_29702
29702
29720
1144
GGAGGACTTGAAAGAGCCA
2347
TGGCTCTTTCAAGTCCTCC

NC_045512.2_19mer_win1_29703
29703
29721
1145
GAGGACTTGAAAGAGCCAC
2348
GTGGCTCTTTCAAGTCCTC

NC_045512.2_19mer_win1_29704
29704
29722
1146
AGGACTTGAAAGAGCCACC
2349
GGTGGCTCTTTCAAGTCCT

NC_045512.2_19mer_win1_29705
29705
29723
1147
GGACTTGAAAGAGCCACCA
2350
TGGTGGCTCTTTCAAGTCC

NC_045512.2_19mer_win1_29706
29706
29724
1148
GACTTGAAAGAGCCACCAC
2351
GTGGTGGCTCTTTCAAGTC

NC_045512.2_19mer_win1_29707
29707
29725
1149
ACTTGAAAGAGCCACCACA
2352
TGTGGTGGCTCTTTCAAGT

NC_045512.2_19mer_win1_29708
29708
29726
1150
CTTGAAAGAGCCACCACAT
2353
ATGTGGTGGCTCTTTCAAG

NC_045512.2_19mer_win1_29709
29709
29727
1151
TTGAAAGAGCCACCACATT
2354
AATGTGGTGGCTCTTTCAA

NC_045512.2_19mer_win1_29710
29710
29728
1152
TGAAAGAGCCACCACATTT
2355
AAATGTGGTGGCTCTTTCA

NC_045512.2_19mer_win1_29711
29711
29729
1153
GAAAGAGCCACCACATTTT
2356
AAAATGTGGTGGCTCTTTC

NC_045512.2_19mer_win1_29712
29712
29730
1154
AAAGAGCCACCACATTTTC
2357
GAAAATGTGGTGGCTCTTT

NC_045512.2_19mer_win1_29713
29713
29731
1155
AAGAGCCACCACATTTTCA
2358
TGAAAATGTGGTGGCTCTT

NC_045512.2_19mer_win1_29733
29733
29751
1156
CGAGGCCACGCGGAGTACG
2359
CGTACTCCGCGTGGCCTCG

NC_045512.2_19mer_win1_29734
29734
29752
1157
GAGGCCACGCGGAGTACGA
2360
TCGTACTCCGCGTGGCCTC

NC_045512.2_19mer_win1_29735
29735
29753
1158
AGGCCACGCGGAGTACGAT
2361
ATCGTACTCCGCGTGGCCT

NC_045512.2_19mer_win1_29736
29736
29754
1159
GGCCACGCGGAGTACGATC
2362
GATCGTACTCCGCGTGGCC

NC_045512.2_19mer_win1_29737
29737
29755
1160
GCCACGCGGAGTACGATCG
2363
CGATCGTACTCCGCGTGGC

NC_045512.2_19mer_win1_29738
29738
29756
1161
CCACGCGGAGTACGATCGA
2364
TCGATCGTACTCCGCGTGG

NC_045512.2_19mer_win1_29739
29739
29757
1162
CACGCGGAGTACGATCGAG
2365
CTCGATCGTACTCCGCGTG

NC_045512.2_19mer_win1_29770
29770
29788
1163
AATGCTAGGGAGAGCTGCC
2366
GGCAGCTCTCCCTAGCATT

NC_045512.2_19mer_win1_29771
29771
29789
1164
ATGCTAGGGAGAGCTGCCT
2367
AGGCAGCTCTCCCTAGCAT

NC_045512.2_19mer_win1_29772
29772
29790
1165
TGCTAGGGAGAGCTGCCTA
2368
TAGGCAGCTCTCCCTAGCA

NC_045512.2_19mer_win1_29773
29773
29791
1166
GCTAGGGAGAGCTGCCTAT
2369
ATAGGCAGCTCTCCCTAGC

NC_045512.2_19mer_win1_29774
29774
29792
1167
CTAGGGAGAGCTGCCTATA
2370
TATAGGCAGCTCTCCCTAG

NC_045512.2_19mer_win1_29775
29775
29793
1168
TAGGGAGAGCTGCCTATAT
2371
ATATAGGCAGCTCTCCCTA

NC_045512.2_19mer_win1_29776
29776
29794
1169
AGGGAGAGCTGCCTATATG
2372
CATATAGGCAGCTCTCCCT

NC_045512.2_19mer_win1_29777
29777
29795
1170
GGGAGAGCTGCCTATATGG
2373
CCATATAGGCAGCTCTCCC

NC_045512.2_19mer_win1_29778
29778
29796
1171
GGAGAGCTGCCTATATGGA
2374
TCCATATAGGCAGCTCTCC

NC_045512.2_19mer_win1_29779
29779
29797
1172
GAGAGCTGCCTATATGGAA
2375
TTCCATATAGGCAGCTCTC

NC_045512.2_19mer_win1_29780
29780
29798
1173
AGAGCTGCCTATATGGAAG
2376
CTTCCATATAGGCAGCTCT

NC_045512.2_19mer_win1_29781
29781
29799
1174
GAGCTGCCTATATGGAAGA
2377
TCTTCCATATAGGCAGCTC

NC_045512.2_19mer_win1_29782
29782
29800
1175
AGCTGCCTATATGGAAGAG
2378
CTCTTCCATATAGGCAGCT

NC_045512.2_19mer_win1_29783
29783
29801
1176
GCTGCCTATATGGAAGAGC
2379
GCTCTTCCATATAGGCAGC

NC_045512.2_19mer_win1_29784
29784
29802
1177
CTGCCTATATGGAAGAGCC
2380
GGCTCTTCCATATAGGCAG

NC_045512.2_19mer_win1_29785
29785
29803
1178
TGCCTATATGGAAGAGCCC
2381
GGGCTCTTCCATATAGGCA

NC_045512.2_19mer_win1_29786
29786
29804
1179
GCCTATATGGAAGAGCCCT
2382
AGGGCTCTTCCATATAGGC

NC_045512.2_19mer_win1_29787
29787
29805
1180
CCTATATGGAAGAGCCCTA
2383
TAGGGCTCTTCCATATAGG

NC_045512.2_19mer_win1_29788
29788
29806
1181
CTATATGGAAGAGCCCTAA
2384
TTAGGGCTCTTCCATATAG

NC_045512.2_19mer_win1_29789
29789
29807
1182
TATATGGAAGAGCCCTAAT
2385
ATTAGGGCTCTTCCATATA

NC_045512.2_19mer_win1_29790
29790
29808
1183
ATATGGAAGAGCCCTAATG
2386
CATTAGGGCTCTTCCATAT

NC_045512.2_19mer_win1_29791
29791
29809
1184
TATGGAAGAGCCCTAATGT
2387
ACATTAGGGCTCTTCCATA

NC_045512.2_19mer_win1_29792
29792
29810
1185
ATGGAAGAGCCCTAATGTG
2388
CACATTAGGGCTCTTCCAT

NC_045512.2_19mer_win1_29793
29793
29811
1186
TGGAAGAGCCCTAATGTGT
2389
ACACATTAGGGCTCTTCCA

NC_045512.2_19mer_win1_29794
29794
29812
1187
GGAAGAGCCCTAATGTGTA
2390
TACACATTAGGGCTCTTCC

NC_045512.2_19mer_win1_29795
29795
29813
1188
GAAGAGCCCTAATGTGTAA
2391
TTACACATTAGGGCTCTTC

NC_045512.2_19mer_win1_29796
29796
29814
1189
AAGAGCCCTAATGTGTAAA
2392
TTTACACATTAGGGCTCTT

NC_045512.2_19mer_win1_29797
29797
29815
1190
AGAGCCCTAATGTGTAAAA
2393
TTTTACACATTAGGGCTCT

NC_045512.2_19mer_win1_29798
29798
29816
1191
GAGCCCTAATGTGTAAAAT
2394
ATTTTACACATTAGGGCTC

NC_045512.2_19mer_win1_29799
29799
29817
1192
AGCCCTAATGTGTAAAATT
2395
AATTTTACACATTAGGGCT

NC_045512.2_19mer_win1_29800
29800
29818
1193
GCCCTAATGTGTAAAATTA
2396
TAATTTTACACATTAGGGC

NC_045512.2_19mer_win1_29801
29801
29819
1194
CCCTAATGTGTAAAATTAA
2397
TTAATTTTACACATTAGGG

NC_045512.2_19mer_win1_29802
29802
29820
1195
CCTAATGTGTAAAATTAAT
2398
ATTAATTTTACACATTAGG

NC_045512.2_19mer_win1_29803
29803
29821
1196
CTAATGTGTAAAATTAATT
2399
AATTAATTTTACACATTAG

NC_045512.2_19mer_win1_29804
29804
29822
1197
TAATGTGTAAAATTAATTT
2400
AAATTAATTTTACACATTA

NC_045512.2_19mer_win1_29805
29805
29823
1198
AATGTGTAAAATTAATTTT
2401
AAAATTAATTTTACACATT

NC_045512.2_19mer_win1_29806
29806
29824
1199
ATGTGTAAAATTAATTTTA
2402
TAAAATTAATTTTACACAT

NC_045512.2_19mer_win1_29807
29807
29825
1200
TGTGTAAAATTAATTTTAG
2403
CTAAAATTAATTTTACACA

NC_045512.2_19mer_win1_29808
29808
29826
1201
GTGTAAAATTAATTTTAGT
2404
ACTAAAATTAATTTTACAC

NC_045512.2_19mer_win1_29809
29809
29827
1202
TGTAAAATTAATTTTAGTA
2405
TACTAAAATTAATTTTACA

NC_045512.2_19mer_win1_29810
29810
29828
1203
GTAAAATTAATTTTAGTAG
2406
CTACTAAAATTAATTTTAC

21-mer Target Sequences

NC_045512.2_21mer_win1_00190
190
210
2411
GACGAATGCCAAAGCAGGCAC
3393
CACGGACGAAACCGTAAGCAG

NC_045512.2_21mer_win1_00191
191
211
2412
ACGAATGCCAAAGCAGGCACA
3394
ACACGGACGAAACCGTAAGCA

NC_045512.2_21mer_win1_00192
192
212
2413
CGAATGCCAAAGCAGGCACAA
3395
AACACGGACGAAACCGTAAGC

NC_045512.2_21mer_win1_00193
193
213
2414
GAATGCCAAAGCAGGCACAAC
3396
CAACACGGACGAAACCGTAAG

NC_045512.2_21mer_win1_00194
194
214
2415
AATGCCAAAGCAGGCACAACG
3397
GCAACACGGACGAAACCGTAA

NC_045512.2_21mer_win1_00195
195
215
2416
ATGCCAAAGCAGGCACAACGT
3398
TGCAACACGGACGAAACCGTA

NC_045512.2_21mer_win1_00196
196
216
2417
TGCCAAAGCAGGCACAACGTC
3399
CTGCAACACGGACGAAACCGT

NC_045512.2_21mer_win1_00233
233
253
2418
GATCCAAAGCAGGCCCACACT
3400
TCACACCCGGACGAAACCTAG

NC_045512.2_21mer_win1_00234
234
254
2419
ATCCAAAGCAGGCCCACACTG
3401
GTCACACCCGGACGAAACCTA

NC_045512.2_21mer_win1_00235
235
255
2420
TCCAAAGCAGGCCCACACTGG
3402
GGTCACACCCGGACGAAACCT

NC_045512.2_21mer_win1_00236
236
256
2421
CCAAAGCAGGCCCACACTGGC
3403
CGGTCACACCCGGACGAAACC

NC_045512.2_21mer_win1_00237
237
257
2422
CAAAGCAGGCCCACACTGGCT
3404
TCGGTCACACCCGGACGAAAC

NC_045512.2_21mer_win1_00238
238
258
2423
AAAGCAGGCCCACACTGGCTT
3405
TTCGGTCACACCCGGACGAAA

NC_045512.2_21mer_win1_00239
239
259
2424
AAGCAGGCCCACACTGGCTTT
3406
TTTCGGTCACACCCGGACGAA

NC_045512.2_21mer_win1_00240
240
260
2425
AGCAGGCCCACACTGGCTTTC
3407
CTTTCGGTCACACCCGGACGA

NC_045512.2_21mer_win1_00241
241
261
2426
GCAGGCCCACACTGGCTTTCC
3408
CCTTTCGGTCACACCCGGACG

NC_045512.2_21mer_win1_00242
242
262
2427
CAGGCCCACACTGGCTTTCCA
3409
ACCTTTCGGTCACACCCGGAC

NC_045512.2_21mer_win1_00243
243
263
2428
AGGCCCACACTGGCTTTCCAT
3410
TACCTTTCGGTCACACCCGGA

NC_045512.2_21mer_win1_00244
244
264
2429
GGCCCACACTGGCTTTCCATT
3411
TTACCTTTCGGTCACACCCGG

NC_045512.2_21mer_win1_00245
245
265
2430
GCCCACACTGGCTTTCCATTC
3412
CTTACCTTTCGGTCACACCCG

NC_045512.2_21mer_win1_00246
246
266
2431
CCCACACTGGCTTTCCATTCT
3413
TCTTACCTTTCGGTCACACCC

NC_045512.2_21mer_win1_00247
247
267
2432
CCACACTGGCTTTCCATTCTA
3414
ATCTTACCTTTCGGTCACACC

NC_045512.2_21mer_win1_00248
248
268
2433
CACACTGGCTTTCCATTCTAC
3415
CATCTTACCTTTCGGTCACAC

NC_045512.2_21mer_win1_00249
249
269
2434
ACACTGGCTTTCCATTCTACC
3416
CCATCTTACCTTTCGGTCACA

NC_045512.2_21mer_win1_00250
250
270
2435
CACTGGCTTTCCATTCTACCT
3417
TCCATCTTACCTTTCGGTCAC

NC_045512.2_21mer_win1_00251
251
271
2436
ACTGGCTTTCCATTCTACCTC
3418
CTCCATCTTACCTTTCGGTCA

NC_045512.2_21mer_win1_00252
252
272
2437
CTGGCTTTCCATTCTACCTCT
3419
TCTCCATCTTACCTTTCGGTC

NC_045512.2_21mer_win1_00253
253
273
2438
TGGCTTTCCATTCTACCTCTC
3420
CTCTCCATCTTACCTTTCGGT

NC_045512.2_21mer_win1_00254
254
274
2439
GGCTTTCCATTCTACCTCTCG
3421
GCTCTCCATCTTACCTTTCGG

NC_045512.2_21mer_win1_00255
255
275
2440
GCTTTCCATTCTACCTCTCGG
3422
GGCTCTCCATCTTACCTTTCG

NC_045512.2_21mer_win1_00256
256
276
2441
CTTTCCATTCTACCTCTCGGA
3423
AGGCTCTCCATCTTACCTTTC

NC_045512.2_21mer_win1_00257
257
277
2442
TTTCCATTCTACCTCTCGGAA
3424
AAGGCTCTCCATCTTACCTTT

NC_045512.2_21mer_win1_00258
258
278
2443
TTCCATTCTACCTCTCGGAAC
3425
CAAGGCTCTCCATCTTACCTT

NC_045512.2_21mer_win1_00259
259
279
2444
TCCATTCTACCTCTCGGAACA
3426
ACAAGGCTCTCCATCTTACCT

NC_045512.2_21mer_win1_00288
288
308
2445
AGTTGCTCTTTTGTGTGCAGG
3427
GGACGTGTGTTTTCTCGTTGA

NC_045512.2_21mer_win1_00289
289
309
2446
GTTGCTCTTTTGTGTGCAGGT
3428
TGGACGTGTGTTTTCTCGTTG

NC_045512.2_21mer_win1_00290
290
310
2447
TTGCTCTTTTGTGTGCAGGTT
3429
TTGGACGTGTGTTTTCTCGTT

NC_045512.2_21mer_win1_00291
291
311
2448
TGCTCTTTTGTGTGCAGGTTG
3430
GTTGGACGTGTGTTTTCTCGT

NC_045512.2_21mer_win1_00292
292
312
2449
GCTCTTTTGTGTGCAGGTTGA
3431
AGTTGGACGTGTGTTTTCTCG

NC_045512.2_21mer_win1_00293
293
313
2450
CTCTTTTGTGTGCAGGTTGAG
3432
GAGTTGGACGTGTGTTTTCTC

NC_045512.2_21mer_win1_00294
294
314
2451
TCTTTTGTGTGCAGGTTGAGT
3433
TGAGTTGGACGTGTGTTTTCT

NC_045512.2_21mer_win1_00295
295
315
2452
CTTTTGTGTGCAGGTTGAGTC
3434
CTGAGTTGGACGTGTGTTTTC

NC_045512.2_21mer_win1_00296
296
316
2453
TTTTGTGTGCAGGTTGAGTCA
3435
ACTGAGTTGGACGTGTGTTTT

NC_045512.2_21mer_win1_00297
297
317
2454
TTTGTGTGCAGGTTGAGTCAA
3436
AACTGAGTTGGACGTGTGTTT

NC_045512.2_21mer_win1_00298
298
318
2455
TTGTGTGCAGGTTGAGTCAAA
3437
AAACTGAGTTGGACGTGTGTT

NC_045512.2_21mer_win1_00299
299
319
2456
TGTGTGCAGGTTGAGTCAAAC
3438
CAAACTGAGTTGGACGTGTGT

NC_045512.2_21mer_win1_00300
300
320
2457
GTGTGCAGGTTGAGTCAAACG
3439
GCAAACTGAGTTGGACGTGTG

NC_045512.2_21mer_win1_00301
301
321
2458
TGTGCAGGTTGAGTCAAACGG
3440
GGCAAACTGAGTTGGACGTGT

NC_045512.2_21mer_win1_00302
302
322
2459
GTGCAGGTTGAGTCAAACGGA
3441
AGGCAAACTGAGTTGGACGTG

NC_045512.2_21mer_win1_00303
303
323
2460
TGCAGGTTGAGTCAAACGGAC
3442
CAGGCAAACTGAGTTGGACGT

NC_045512.2_21mer_win1_00304
304
324
2461
GCAGGTTGAGTCAAACGGACA
3443
ACAGGCAAACTGAGTTGGACG

NC_045512.2_21mer_win1_00455
455
475
2462
GAACTTGTCGGGATACACAAG
3444
GAACACATAGGGCTGTTCAAG

NC_045512.2_21mer_win1_00456
456
476
2463
AACTTGTCGGGATACACAAGT
3445
TGAACACATAGGGCTGTTCAA

NC_045512.2_21mer_win1_00457
457
477
2464
ACTTGTCGGGATACACAAGTA
3446
ATGAACACATAGGGCTGTTCA

NC_045512.2_21mer_win1_00626
626
646
2465
CAAGAAGAAGCATTCTTGCCA
3447
ACCGTTCTTACGAAGAAGAAC

NC_045512.2_21mer_win1_00627
627
647
2466
AAGAAGAAGCATTCTTGCCAT
3448
TACCGTTCTTACGAAGAAGAA

NC_045512.2_21mer_win1_00628
628
648
2467
AGAAGAAGCATTCTTGCCATT
3449
TTACCGTTCTTACGAAGAAGA

NC_045512.2_21mer_win1_00629
629
649
2468
GAAGAAGCATTCTTGCCATTA
3450
ATTACCGTTCTTACGAAGAAG

NC_045512.2_21mer_win1_00630
630
650
2469
AAGAAGCATTCTTGCCATTAT
3451
TATTACCGTTCTTACGAAGAA

NC_045512.2_21mer_win1_00631
631
651
2470
AGAAGCATTCTTGCCATTATT
3452
TTATTACCGTTCTTACGAAGA

NC_045512.2_21mer_win1_03352
3352
3372
2471
ACCAATAAATTTTGAATGACT
3453
TCAGTAAGTTTTAAATAACCA

NC_045512.2_21mer_win1_03353
3353
3373
2472
CCAATAAATTTTGAATGACTG
3454
GTCAGTAAGTTTTAAATAACC

NC_045512.2_21mer_win1_03354
3354
3374
2473
CAATAAATTTTGAATGACTGT
3455
TGTCAGTAAGTTTTAAATAAC

NC_045512.2_21mer_win1_03355
3355
3375
2474
AATAAATTTTGAATGACTGTT
3456
TTGTCAGTAAGTTTTAAATAA

NC_045512.2_21mer_win1_03356
3356
3376
2475
ATAAATTTTGAATGACTGTTA
3457
ATTGTCAGTAAGTTTTAAATA

NC_045512.2_21mer_win1_03357
3357
3377
2476
TAAATTTTGAATGACTGTTAC
3458
CATTGTCAGTAAGTTTTAAAT

NC_045512.2_21mer_win1_03358
3358
3378
2477
AAATTTTGAATGACTGTTACA
3459
ACATTGTCAGTAAGTTTTAAA

NC_045512.2_21mer_win1_06406
6406
6426
2478
GAGACTTCTTCATCACCTTTT
3460
TTTTCCACTACTTCTTCAGAG

NC_045512.2_21mer_win1_06407
6407
6427
2479
AGACTTCTTCATCACCTTTTA
3461
ATTTTCCACTACTTCTTCAGA

NC_045512.2_21mer_win1_06408
6408
6428
2480
GACTTCTTCATCACCTTTTAG
3462
GATTTTCCACTACTTCTTCAG

NC_045512.2_21mer_win1_06409
6409
6429
2481
ACTTCTTCATCACCTTTTAGG
3463
GGATTTTCCACTACTTCTTCA

NC_045512.2_21mer_win1_06410
6410
6430
2482
CTTCTTCATCACCTTTTAGGA
3464
AGGATTTTCCACTACTTCTTC

NC_045512.2_21mer_win1_06411
6411
6431
2483
TTCTTCATCACCTTTTAGGAT
3465
TAGGATTTTCCACTACTTCTT

NC_045512.2_21mer_win1_06412
6412
6432
2484
TCTTCATCACCTTTTAGGATG
3466
GTAGGATTTTCCACTACTTCT

NC_045512.2_21mer_win1_06413
6413
6433
2485
CTTCATCACCTTTTAGGATGG
3467
GGTAGGATTTTCCACTACTTC

NC_045512.2_21mer_win1_06461
6461
6481
2486
CACTTTTGATGGCTTCAACAT
3468
TACAACTTCGGTAGTTTTCAC

NC_045512.2_21mer_win1_06462
6462
6482
2487
ACTTTTGATGGCTTCAACATC
3469
CTACAACTTCGGTAGTTTTCA

NC_045512.2_21mer_win1_06463
6463
6483
2488
CTTTTGATGGCTTCAACATCC
3470
CCTACAACTTCGGTAGTTTTC

NC_045512.2_21mer_win1_10484
10484
10504
2489
AGTACACCATCACAACCAAAA
3471
AAAACCAACACTACCACATGA

NC_045512.2_21mer_win1_10485
10485
10505
2490
GTACACCATCACAACCAAAAT
3472
TAAAACCAACACTACCACATG

NC_045512.2_21mer_win1_10486
10486
10506
2491
TACACCATCACAACCAAAATT
3473
TTAAAACCAACACTACCACAT

NC_045512.2_21mer_win1_10487
10487
10507
2492
ACACCATCACAACCAAAATTG
3474
GTTAAAACCAACACTACCACA

NC_045512.2_21mer_win1_10488
10488
10508
2493
CACCATCACAACCAAAATTGT
3475
TGTTAAAACCAACACTACCAC

NC_045512.2_21mer_win1_10489
10489
10509
2494
ACCATCACAACCAAAATTGTA
3476
ATGTTAAAACCAACACTACCA

NC_045512.2_21mer_win1_11609
11609
11629
2495
CAAATAACAAAGAATCCGATA
3477
ATAGCCTAAGAAACAATAAAC

NC_045512.2_21mer_win1_11610
11610
11630
2496
AAATAACAAAGAATCCGATAA
3478
AATAGCCTAAGAAACAATAAA

NC_045512.2_21mer_win1_12023
12023
12043
2497
AGGTACGTCCCACGACATCTG
3479
GTCTACAGCACCCTGCATGGA

NC_045512.2_21mer_win1_12024
12024
12044
2498
GGTACGTCCCACGACATCTGT
3480
TGTCTACAGCACCCTGCATGG

NC_045512.2_21mer_win1_12025
12025
12045
2499
GTACGTCCCACGACATCTGTA
3481
ATGTCTACAGCACCCTGCATG

NC_045512.2_21mer_win1_12212
12212
12232
2500
AGAAACTTACACCGATTTAGA
3482
AGATTTAGCCACATTCAAAGA

NC_045512.2_21mer_win1_12213
12213
12233
2501
GAAACTTACACCGATTTAGAC
3483
CAGATTTAGCCACATTCAAAG

NC_045512.2_21mer_win1_12214
12214
12234
2502
AAACTTACACCGATTTAGACT
3484
TCAGATTTAGCCACATTCAAA

NC_045512.2_21mer_win1_12839
12839
12859
2503
TTTACCCGATCTAAGGGATTC
3485
CTTAGGGAATCTAGCCCATTT

NC_045512.2_21mer_win1_12840
12840
12860
2504
TTACCCGATCTAAGGGATTCT
3486
TCTTAGGGAATCTAGCCCATT

NC_045512.2_21mer_win1_12841
12841
12861
2505
TACCCGATCTAAGGGATTCTC
3487
CTCTTAGGGAATCTAGCCCAT

NC_045512.2_21mer_win1_12842
12842
12862
2506
ACCCGATCTAAGGGATTCTCA
3488
ACTCTTAGGGAATCTAGCCCA

NC_045512.2_21mer_win1_12843
12843
12863
2507
CCCGATCTAAGGGATTCTCAC
3489
CACTCTTAGGGAATCTAGCCC

NC_045512.2_21mer_win1_12844
12844
12864
2508
CCGATCTAAGGGATTCTCACT
3490
TCACTCTTAGGGAATCTAGCC

NC_045512.2_21mer_win1_12845
12845
12865
2509
CGATCTAAGGGATTCTCACTA
3491
ATCACTCTTAGGGAATCTAGC

NC_045512.2_21mer_win1_12846
12846
12866
2510
GATCTAAGGGATTCTCACTAC
3492
CATCACTCTTAGGGAATCTAG

NC_045512.2_21mer_win1_12847
12847
12867
2511
ATCTAAGGGATTCTCACTACC
3493
CCATCACTCTTAGGGAATCTA

NC_045512.2_21mer_win1_12885
12885
12905
2512
GTCTTGACCTTGGTGGAACAT
3494
TACAAGGTGGTTCCAGTTCTG

NC_045512.2_21mer_win1_12886
12886
12906
2513
TCTTGACCTTGGTGGAACATC
3495
CTACAAGGTGGTTCCAGTTCT

NC_045512.2_21mer_win1_12887
12887
12907
2514
CTTGACCTTGGTGGAACATCC
3496
CCTACAAGGTGGTTCCAGTTC

NC_045512.2_21mer_win1_12888
12888
12908
2515
TTGACCTTGGTGGAACATCCA
3497
ACCTACAAGGTGGTTCCAGTT

NC_045512.2_21mer_win1_12889
12889
12909
2516
TGACCTTGGTGGAACATCCAA
3498
AACCTACAAGGTGGTTCCAGT

NC_045512.2_21mer_win1_12890
12890
12910
2517
GACCTTGGTGGAACATCCAAA
3499
AAACCTACAAGGTGGTTCCAG

NC_045512.2_21mer_win1_12891
12891
12911
2518
ACCTTGGTGGAACATCCAAAC
3500
CAAACCTACAAGGTGGTTCCA

NC_045512.2_2lmer_win1_12892
12892
12912
2519
CCTTGGTGGAACATCCAAACA
3501
ACAAACCTACAAGGTGGTTCC

NC_045512.2_2lmer_win1_12893
12893
12913
2520
CTTGGTGGAACATCCAAACAA
3502
AACAAACCTACAAGGTGGTTC

NC_045512.2_2lmer_win1_12894
12894
12914
2521
TTGGTGGAACATCCAAACAAT
3503
TAACAAACCTACAAGGTGGTT

NC_045512.2_2lmer_win1_12895
12895
12915
2522
TGGTGGAACATCCAAACAATG
3504
GTAACAAACCTACAAGGTGGT

NC_045512.2_2lmer_win1_12896
12896
12916
2523
GGTGGAACATCCAAACAATGT
3505
TGTAACAAACCTACAAGGTGG

NC_045512.2_2lmer_win1_12897
12897
12917
2524
GTGGAACATCCAAACAATGTC
3506
CTGTAACAAACCTACAAGGTG

NC_045512.2_2lmer_win1_12898
12898
12918
2525
TGGAACATCCAAACAATGTCT
3507
TCTGTAACAAACCTACAAGGT

NC_045512.2_2lmer_win1_12899
12899
12919
2526
GGAACATCCAAACAATGTCTG
3508
GTCTGTAACAAACCTACAAGG

NC_045512.2_21mer_win1_12900
12900
12920
2527
GAACATCCAAACAATGTCTGT
3509
TGTCTGTAACAAACCTACAAG

NC_045512.2_2lmer_win1_12901
12901
12921
2528
AACATCCAAACAATGTCTGTG
3510
GTGTCTGTAACAAACCTACAA

NC_045512.2_2lmer_win1_12902
12902
12922
2529
ACATCCAAACAATGTCTGTGT
3511
TGTGTCTGTAACAAACCTACA

NC_045512.2_2lmer_win1_12903
12903
12923
2530
CATCCAAACAATGTCTGTGTG
3512
GTGTGTCTGTAACAAACCTAC

NC_045512.2_2lmer_win1_12904
12904
12924
2531
ATCCAAACAATGTCTGTGTGG
3513
GGTGTGTCTGTAACAAACCTA

NC_045512.2_2lmer_win1_12966
12966
12986
2532
ATTTGTTGGATTTATCTCCAT
3514
TACCTCTATTTAGGTTGTTTA

NC_045512.2_2lmer_win1_12967
12967
12987
2533
TTTGTTGGATTTATCTCCATA
3515
ATACCTCTATTTAGGTTGTTT

NC_045512.2_2lmer_win1_12968
12968
12988
2534
TTGTTGGATTTATCTCCATAC
3516
CATACCTCTATTTAGGTTGTT

NC_045512.2_2lmer_win1_12969
12969
12989
2535
TGTTGGATTTATCTCCATACC
3517
CCATACCTCTATTTAGGTTGT

NC_045512.2_2lmer_win1_12970
12970
12990
2536
GTTGGATTTATCTCCATACCA
3518
ACCATACCTCTATTTAGGTTG

NC_045512.2_2lmer_win1_13151
13151
13171
2537
TTCTACAACACATGTGTGTGA
3519
AGTGTGTGTACACAACATCTT

NC_045512.2_2lmer_win1_13152
13152
13172
2538
TCTACAACACATGTGTGTGAC
3520
CAGTGTGTGTACACAACATCT

NC_045512.2_2lmer_win1_13153
13153
13173
2539
CTACAACACATGTGTGTGACC
3521
CCAGTGTGTGTACACAACATC

NC_045512.2_2lmer_win1_13154
13154
13174
2540
TACAACACATGTGTGTGACCA
3522
ACCAGTGTGTGTACACAACAT

NC_045512.2_2lmer_win1_13155
13155
13175
2541
ACAACACATGTGTGTGACCAT
3523
TACCAGTGTGTGTACACAACA

NC_045512.2_21mer_win1_13156
13156
13176
2542
CAACACATGTGTGTGACCATG
3524
GTACCAGTGTGTGTACACAAC

NC_045512.2_21mer_win1_13363
13363
13383
2543
TTTGTGTCAGACATGGCAGAC
3525
CAGACGGTACAGACTGTGTTT

NC_045512.2_21mer_win1_13364
13364
13384
2544
TTGTGTCAGACATGGCAGACG
3526
GCAGACGGTACAGACTGTGTT

NC_045512.2_21mer_win1_13365
13365
13385
2545
TGTGTCAGACATGGCAGACGC
3527
CGCAGACGGTACAGACTGTGT

NC_045512.2_21mer_win1_13366
13366
13386
2546
GTGTCAGACATGGCAGACGCC
3528
CCGCAGACGGTACAGACTGTG

NC_045512.2_21mer_win1_13388
13388
13408
2547
TACACCTTTCCAATACCGACA
3529
ACAGCCATAACCTTTCCACAT

NC_045512.2_21mer_win1_13389
13389
13409
2548
ACACCTTTCCAATACCGACAT
3530
TACAGCCATAACCTTTCCACA

NC_045512.2_21mer_win1_13390
13390
13410
2549
CACCTTTCCAATACCGACATC
3531
CTACAGCCATAACCTTTCCAC

NC_045512.2_21mer_win1_13391
13391
13411
2550
ACCTTTCCAATACCGACATCA
3532
ACTACAGCCATAACCTTTCCA

NC_045512.2_21mer_win1_13392
13392
13412
2551
CCTTTCCAATACCGACATCAA
3533
AACTACAGCCATAACCTTTCC

NC_045512.2_21mer_win1_13393
13393
13413
2552
CTTTCCAATACCGACATCAAC
3534
CAACTACAGCCATAACCTTTC

NC_045512.2_21mer_win1_13394
13394
13414
2553
TTTCCAATACCGACATCAACA
3535
ACAACTACAGCCATAACCTTT

NC_045512.2_21mer_win1_13395
13395
13415
2554
TTCCAATACCGACATCAACAC
3536
CACAACTACAGCCATAACCTT

NC_045512.2_21mer_win1_13396
13396
13416
2555
TCCAATACCGACATCAACACT
3537
TCACAACTACAGCCATAACCT

NC_045512.2_21mer_win1_13458
13458
13478
2556
GCAAAAATTTGCCCAAACGCC
3538
CCGCAAACCCGTTTAAAAACG

NC_045512.2_21mer_win1_13459
13459
13479
2557
CAAAAATTTGCCCAAACGCCA
3539
ACCGCAAACCCGTTTAAAAAC

NC_045512.2_21mer_win1_13460
13460
13480
2558
AAAAATTTGCCCAAACGCCAC
3540
CACCGCAAACCCGTTTAAAAA

NC_045512.2_21mer_win1_13461
13461
13481
2559
AAAATTTGCCCAAACGCCACA
3541
ACACCGCAAACCCGTTTAAAA

NC_045512.2_21mer_win1_13462
13462
13482
2560
AAATTTGCCCAAACGCCACAT
3542
TACACCGCAAACCCGTTTAAA

NC_045512.2_21mer_win1_13463
13463
13483
2561
AATTTGCCCAAACGCCACATT
3543
TTACACCGCAAACCCGTTTAA

NC_045512.2_21mer_win1_13464
13464
13484
2562
ATTTGCCCAAACGCCACATTC
3544
CTTACACCGCAAACCCGTTTA

NC_045512.2_21mer_win1_13465
13465
13485
2563
TTTGCCCAAACGCCACATTCA
3545
ACTTACACCGCAAACCCGTTT

NC_045512.2_21mer_win1_13466
13466
13486
2564
TTGCCCAAACGCCACATTCAC
3546
CACTTACACCGCAAACCCGTT

NC_045512.2_21mer_win1_13467
13467
13487
2565
TGCCCAAACGCCACATTCACG
3547
GCACTTACACCGCAAACCCGT

NC_045512.2_21mer_win1_13468
13468
13488
2566
GCCCAAACGCCACATTCACGT
3548
TGCACTTACACCGCAAACCCG

NC_045512.2_21mer_win1_13469
13469
13489
2567
CCCAAACGCCACATTCACGTC
3549
CTGCACTTACACCGCAAACCC

NC_045512.2_21mer_win1_13470
13470
13490
2568
CCAAACGCCACATTCACGTCG
3550
GCTGCACTTACACCGCAAACC

NC_045512.2_21mer_win1_13471
13471
13491
2569
CAAACGCCACATTCACGTCGG
3551
GGCTGCACTTACACCGCAAAC

NC_045512.2_21mer_win1_13472
13472
13492
2570
AAACGCCACATTCACGTCGGG
3552
GGGCTGCACTTACACCGCAAA

NC_045512.2_21mer_win1_13473
13473
13493
2571
AACGCCACATTCACGTCGGGC
3553
CGGGCTGCACTTACACCGCAA

NC_045512.2_21mer_win1_13474
13474
13494
2572
ACGCCACATTCACGTCGGGCA
3554
ACGGGCTGCACTTACACCGCA

NC_045512.2_21mer_win1_13475
13475
13495
2573
CGCCACATTCACGTCGGGCAG
3555
GACGGGCTGCACTTACACCGC

NC_045512.2_21mer_win1_13476
13476
13496
2574
GCCACATTCACGTCGGGCAGA
3556
AGACGGGCTGCACTTACACCG

NC_045512.2_21mer_win1_13477
13477
13497
2575
CCACATTCACGTCGGGCAGAA
3557
AAGACGGGCTGCACTTACACC

NC_045512.2_21mer_win1_13478
13478
13498
2576
CACATTCACGTCGGGCAGAAT
3558
TAAGACGGGCTGCACTTACAC

NC_045512.2_21mer_win1_13479
13479
13499
2577
ACATTCACGTCGGGCAGAATG
3559
GTAAGACGGGCTGCACTTACA

NC_045512.2_21mer_win1_13480
13480
13500
2578
CATTCACGTCGGGCAGAATGT
3560
TGTAAGACGGGCTGCACTTAC

NC_045512.2_21mer_win1_13481
13481
13501
2579
ATTCACGTCGGGCAGAATGTG
3561
GTGTAAGACGGGCTGCACTTA

NC_045512.2_21mer_win1_13482
13482
13502
2580
TTCACGTCGGGCAGAATGTGG
3562
GGTGTAAGACGGGCTGCACTT

NC_045512.2_21mer_win1_13483
13483
13503
2581
TCACGTCGGGCAGAATGTGGC
3563
CGGTGTAAGACGGGCTGCACT

NC_045512.2_21mer_win1_13484
13484
13504
2582
CACGTCGGGCAGAATGTGGCA
3564
ACGGTGTAAGACGGGCTGCAC

NC_045512.2_21mer_win1_13485
13485
13505
2583
ACGTCGGGCAGAATGTGGCAC
3565
CACGGTGTAAGACGGGCTGCA

NC_045512.2_21mer_win1_13486
13486
13506
2584
CGTCGGGCAGAATGTGGCACG
3566
GCACGGTGTAAGACGGGCTGC

NC_045512.2_21mer_win1_13487
13487
13507
2585
GTCGGGCAGAATGTGGCACGC
3567
CGCACGGTGTAAGACGGGCTG

NC_045512.2_21mer_win1_13488
13488
13508
2586
TCGGGCAGAATGTGGCACGCC
3568
CCGCACGGTGTAAGACGGGCT

NC_045512.2_21mer_win1_13489
13489
13509
2587
CGGGCAGAATGTGGCACGCCG
3569
GCCGCACGGTGTAAGACGGGC

NC_045512.2_21mer_win1_13490
13490
13510
2588
GGGCAGAATGTGGCACGCCGT
3570
TGCCGCACGGTGTAAGACGGG

NC_045512.2_21mer_win1_13491
13491
13511
2589
GGCAGAATGTGGCACGCCGTG
3571
GTGCCGCACGGTGTAAGACGG

NC_045512.2_21mer_win1_13492
13492
13512
2590
GCAGAATGTGGCACGCCGTGT
3572
TGTGCCGCACGGTGTAAGACG

NC_045512.2_21mer_win1_13493
13493
13513
2591
CAGAATGTGGCACGCCGTGTC
3573
CTGTGCCGCACGGTGTAAGAC

NC_045512.2_21mer_win1_13494
13494
13514
2592
AGAATGTGGCACGCCGTGTCC
3574
CCTGTGCCGCACGGTGTAAGA

NC_045512.2_21mer_win1_13495
13495
13515
2593
GAATGTGGCACGCCGTGTCCG
3575
GCCTGTGCCGCACGGTGTAAG

NC_045512.2_21mer_win1_13496
13496
13516
2594
AATGTGGCACGCCGTGTCCGT
3576
TGCCTGTGCCGCACGGTGTAA

NC_045512.2_21mer_win1_13497
13497
13517
2595
ATGTGGCACGCCGTGTCCGTG
3577
GTGCCTGTGCCGCACGGTGTA

NC_045512.2_21mer_win1_13498
13498
13518
2596
TGTGGCACGCCGTGTCCGTGA
3578
AGTGCCTGTGCCGCACGGTGT

NC_045512.2_21mer_win1_13499
13499
13519
2597
GTGGCACGCCGTGTCCGTGAT
3579
TAGTGCCTGTGCCGCACGGTG

NC_045512.2_21mer_win1_13500
13500
13520
2598
TGGCACGCCGTGTCCGTGATC
3580
CTAGTGCCTGTGCCGCACGGT

NC_045512.2_21mer_win1_13762
13762
13782
2599
CCACTGTACCATGGTGTATAT
3581
TATATGTGGTACCATGTCACC

NC_045512.2_21mer_win1_13763
13763
13783
2600
CACTGTACCATGGTGTATATA
3582
ATATATGTGGTACCATGTCAC

NC_045512.2_21mer_win1_13764
13764
13784
2601
ACTGTACCATGGTGTATATAG
3583
GATATATGTGGTACCATGTCA

NC_045512.2_21mer_win1_13765
13765
13785
2602
CTGTACCATGGTGTATATAGT
3584
TGATATATGTGGTACCATGTC

NC_045512.2_21mer_win1_13766
13766
13786
2603
TGTACCATGGTGTATATAGTG
3585
GTGATATATGTGGTACCATGT

NC_045512.2_21mer_win1_13767
13767
13787
2604
GTACCATGGTGTATATAGTGC
3586
CGTGATATATGTGGTACCATG

NC_045512.2_21mer_win1_13768
13768
13788
2605
TACCATGGTGTATATAGTGCA
3587
ACGTGATATATGTGGTACCAT

NC_045512.2_21mer_win1_13769
13769
13789
2606
ACCATGGTGTATATAGTGCAG
3588
GACGTGATATATGTGGTACCA

NC_045512.2_21mer_win1_13770
13770
13790
2607
CCATGGTGTATATAGTGCAGT
3589
TGACGTGATATATGTGGTACC

NC_045512.2_21mer_win1_14290
14290
14310
2608
CTGGCAATAAAATTTATAACC
3590
CCAATATTTAAAATAACGGTC

NC_045512.2_21mer_win1_14291
14291
14311
2609
TGGCAATAAAATTTATAACCC
3591
CCCAATATTTAAAATAACGGT

NC_045512.2_21mer_win1_14292
14292
14312
2610
GGCAATAAAATTTATAACCCT
3592
TCCCAATATTTAAAATAACGG

NC_045512.2_21mer_win1_14404
14404
14424
2611
GGTGGATGTTCAAAACCTGGT
3593
TGGTCCAAAACTTGTAGGTGG

NC_045512.2_2lmer_win1_14405
14405
14425
2612
GTGGATGTTCAAAACCTGGTG
3594
GTGGTCCAAAACTTGTAGGTG

NC_045512.2_21mer_win1_14406
14406
14426
2613
TGGATGTTCAAAACCTGGTGA
3595
AGTGGTCCAAAACTTGTAGGT

NC_045512.2_21mer_win1_14407
14407
14427
2614
GGATGTTCAAAACCTGGTGAT
3596
TAGTGGTCCAAAACTTGTAGG

NC_045512.2_2lmer_win1_14408
14408
14428
2615
GATGTTCAAAACCTGGTGATC
3597
CTAGTGGTCCAAAACTTGTAG

NC_045512.2_2lmer_win1_14409
14409
14429
2616
ATGTTCAAAACCTGGTGATCA
3598
ACTAGTGGTCCAAAACTTGTA

NC_045512.2_2lmer_win1_14500
14500
14520
2617
CATGTATTAGTCCTACATTTG
3599
GTTTACATCCTGATTATGTAC

NC_045512.2_2lmer_win1_14501
14501
14521
2618
ATGTATTAGTCCTACATTTGA
3600
AGTTTACATCCTGATTATGTA

NC_045512.2_2lmer_win1_14502
14502
14522
2619
TGTATTAGTCCTACATTTGAA
3601
AAGTTTACATCCTGATTATGT

NC_045512.2_2lmer_win1_14503
14503
14523
2620
GTATTAGTCCTACATTTGAAT
3602
TAAGTTTACATCCTGATTATG

NC_045512.2_2lmer_win1_14504
14504
14524
2621
TATTAGTCCTACATTTGAATG
3603
GTAAGTTTACATCCTGATTAT

NC_045512.2_2lmer_win1_14505
14505
14525
2622
ATTAGTCCTACATTTGAATGT
3604
TGTAAGTTTACATCCTGATTA

NC_045512.2_2lmer_win1_14506
14506
14526
2623
TTAGTCCTACATTTGAATGTA
3605
ATGTAAGTTTACATCCTGATT

NC_045512.2_2lmer_win1_14507
14507
14527
2624
TAGTCCTACATTTGAATGTAT
3606
TATGTAAGTTTACATCCTGAT

NC_045512.2_2lmer_win1_14508
14508
14528
2625
AGTCCTACATTTGAATGTATC
3607
CTATGTAAGTTTACATCCTGA

NC_045512.2_2lmer_win1_14509
14509
14529
2626
GTCCTACATTTGAATGTATCG
3608
GCTATGTAAGTTTACATCCTG

NC_045512.2_2lmer_win1_14510
14510
14530
2627
TCCTACATTTGAATGTATCGA
3609
AGCTATGTAAGTTTACATCCT

NC_045512.2_2lmer_win1_14511
14511
14531
2628
CCTACATTTGAATGTATCGAG
3610
GAGCTATGTAAGTTTACATCC

NC_045512.2_2lmer_win1_14650
14650
14670
2629
TTACAACGAAAAGTTTGACAG
3611
GACAGTTTGAAAAGCAACATT

NC_045512.2_2lmer_win1_14651
14651
14671
2630
TACAACGAAAAGTTTGACAGT
3612
TGACAGTTTGAAAAGCAACAT

NC_045512.2_2lmer_win1_14652
14652
14672
2631
ACAACGAAAAGTTTGACAGTT
3613
TTGACAGTTTGAAAAGCAACA

NC_045512.2_2lmer_win1_14653
14653
14673
2632
CAACGAAAAGTTTGACAGTTT
3614
TTTGACAGTTTGAAAAGCAAC

NC_045512.2_2lmer_win1_14654
14654
14674
2633
AACGAAAAGTTTGACAGTTTG
3615
GTTTGACAGTTTGAAAAGCAA

NC_045512.2_21mer_win1_14655
14655
14675
2634
ACGAAAAGTTTGACAGTTTGG
3616
GGTTTGACAGTTTGAAAAGCA

NC_045512.2_21mer_win1_14656
14656
14676
2635
CGAAAAGTTTGACAGTTTGGG
3617
GGGTTTGACAGTTTGAAAAGC

NC_045512.2_21mer_win1_14657
14657
14677
2636
GAAAAGTTTGACAGTTTGGGC
3618
CGGGTTTGACAGTTTGAAAAG

NC_045512.2_21mer_win1_14658
14658
14678
2637
AAAAGTTTGACAGTTTGGGCC
3619
CCGGGTTTGACAGTTTGAAAA

NC_045512.2_21mer_win1_14659
14659
14679
2638
AAAGTTTGACAGTTTGGGCCA
3620
ACCGGGTTTGACAGTTTGAAA

NC_045512.2_21mer_win1_14660
14660
14680
2639
AAGTTTGACAGTTTGGGCCAT
3621
TACCGGGTTTGACAGTTTGAA

NC_045512.2_21mer_win1_14661
14661
14681
2640
AGTTTGACAGTTTGGGCCATT
3622
TTACCGGGTTTGACAGTTTGA

NC_045512.2_21mer_win1_14662
14662
14682
2641
GTTTGACAGTTTGGGCCATTA
3623
ATTACCGGGTTTGACAGTTTG

NC_045512.2_21mer_win1_14663
14663
14683
2642
TTTGACAGTTTGGGCCATTAA
3624
AATTACCGGGTTTGACAGTTT

NC_045512.2_21mer_win1_14664
14664
14684
2643
TTGACAGTTTGGGCCATTAAA
3625
AAATTACCGGGTTTGACAGTT

NC_045512.2_21mer_win1_14665
14665
14685
2644
TGACAGTTTGGGCCATTAAAA
3626
AAAATTACCGGGTTTGACAGT

NC_045512.2_21mer_win1_14666
14666
14686
2645
GACAGTTTGGGCCATTAAAAT
3627
TAAAATTACCGGGTTTGACAG

NC_045512.2_21mer_win1_14667
14667
14687
2646
ACAGTTTGGGCCATTAAAATT
3628
TTAAAATTACCGGGTTTGACA

NC_045512.2_21mer_win1_14722
14722
14742
2647
AAGAAATTCCTTCCTTCAAGA
3629
AGAACTTCCTTCCTTAAAGAA

NC_045512.2_21mer_win1_14723
14723
14743
2648
AGAAATTCCTTCCTTCAAGAC
3630
CAGAACTTCCTTCCTTAAAGA

NC_045512.2_21mer_win1_14724
14724
14744
2649
GAAATTCCTTCCTTCAAGACA
3631
ACAGAACTTCCTTCCTTAAAG

NC_045512.2_21mer_win1_14725
14725
14745
2650
AAATTCCTTCCTTCAAGACAA
3632
AACAGAACTTCCTTCCTTAAA

NC_045512.2_21mer_win1_14726
14726
14746
2651
AATTCCTTCCTTCAAGACAAC
3633
CAACAGAACTTCCTTCCTTAA

NC_045512.2_21mer_win1_14727
14727
14747
2652
ATTCCTTCCTTCAAGACAACT
3634
TCAACAGAACTTCCTTCCTTA

NC_045512.2_21mer_win1_14728
14728
14748
2653
TTCCTTCCTTCAAGACAACTT
3635
TTCAACAGAACTTCCTTCCTT

NC_045512.2_21mer_win1_14750
14750
14770
2654
ATTTTGTGAAGAAGAAACGAG
3636
GAGCAAAGAAGAAGTGTTTTA

NC_045512.2_21mer_win1_14751
14751
14771
2655
TTTTGTGAAGAAGAAACGAGT
3637
TGAGCAAAGAAGAAGTGTTTT

NC_045512.2_21mer_win1_14752
14752
14772
2656
TTTGTGAAGAAGAAACGAGTC
3638
CTGAGCAAAGAAGAAGTGTTT

NC_045512.2_21mer_win1_14753
14753
14773
2657
TTGTGAAGAAGAAACGAGTCC
3639
CCTGAGCAAAGAAGAAGTGTT

NC_045512.2_21mer_win1_14754
14754
14774
2658
TGTGAAGAAGAAACGAGTCCT
3640
TCCTGAGCAAAGAAGAAGTGT

NC_045512.2_21mer_win1_14755
14755
14775
2659
GTGAAGAAGAAACGAGTCCTA
3641
ATCCTGAGCAAAGAAGAAGTG

NC_045512.2_21mer_win1_14756
14756
14776
2660
TGAAGAAGAAACGAGTCCTAC
3642
CATCCTGAGCAAAGAAGAAGT

NC_045512.2_21mer_win1_14757
14757
14777
2661
GAAGAAGAAACGAGTCCTACC
3643
CCATCCTGAGCAAAGAAGAAG

NC_045512.2_21mer_win1_14821
14821
14841
2662
GGTTGTTACACACTATAGTCT
3644
TCTGATATCACACATTGTTGG

NC_045512.2_21mer_win1_14822
14822
14842
2663
GTTGTTACACACTATAGTCTG
3645
GTCTGATATCACACATTGTTG

NC_045512.2_21mer_win1_14823
14823
14843
2664
TTGTTACACACTATAGTCTGT
3646
TGTCTGATATCACACATTGTT

NC_045512.2_21mer_win1_14824
14824
14844
2665
TGTTACACACTATAGTCTGTT
3647
TTGTCTGATATCACACATTGT

NC_045512.2_21mer_win1_14825
14825
14845
2666
GTTACACACTATAGTCTGTTG
3648
GTTGTCTGATATCACACATTG

NC_045512.2_21mer_win1_14826
14826
14846
2667
TTACACACTATAGTCTGTTGA
3649
AGTTGTCTGATATCACACATT

NC_045512.2_21mer_win1_14875
14875
14895
2668
ATGAAACTAACAATGCTACCA
3650
ACCATCGTAACAATCAAAGTA

NC_045512.2_21mer_win1_14876
14876
14896
2669
TGAAACTAACAATGCTACCAC
3651
CACCATCGTAACAATCAAAGT

NC_045512.2_21mer_win1_14877
14877
14897
2670
GAAACTAACAATGCTACCACC
3652
CCACCATCGTAACAATCAAAG

NC_045512.2_21mer_win1_14878
14878
14898
2671
AAACTAACAATGCTACCACCG
3653
GCCACCATCGTAACAATCAAA

NC_045512.2_21mer_win1_14879
14879
14899
2672
AACTAACAATGCTACCACCGA
3654
AGCCACCATCGTAACAATCAA

NC_045512.2_21mer_win1_14880
14880
14900
2673
ACTAACAATGCTACCACCGAC
3655
CAGCCACCATCGTAACAATCA

NC_045512.2_21mer_win1_14881
14881
14901
2674
CTAACAATGCTACCACCGACA
3656
ACAGCCACCATCGTAACAATC

NC_045512.2_21mer_win1_14882
14882
14902
2675
TAACAATGCTACCACCGACAT
3657
TACAGCCACCATCGTAACAAT

NC_045512.2_21mer_win1_14883
14883
14903
2676
AACAATGCTACCACCGACATA
3658
ATACAGCCACCATCGTAACAA

NC_045512.2_21mer_win1_14962
14962
14982
2677
TTTACCCCATTCCGATCTGAA
3659
AAGTCTAGCCTTACCCCATTT

NC_045512.2_21mer_win1_14963
14963
14983
2678
TTACCCCATTCCGATCTGAAA
3660
AAAGTCTAGCCTTACCCCATT

NC_045512.2_21mer_win1_14964
14964
14984
2679
TACCCCATTCCGATCTGAAAT
3661
TAAAGTCTAGCCTTACCCCAT

NC_045512.2_21mer_win1_14965
14965
14985
2680
ACCCCATTCCGATCTGAAATA
3662
ATAAAGTCTAGCCTTACCCCA

NC_045512.2_21mer_win1_14966
14966
14986
2681
CCCCATTCCGATCTGAAATAA
3663
AATAAAGTCTAGCCTTACCCC

NC_045512.2_21mer_win1_14967
14967
14987
2682
CCCATTCCGATCTGAAATAAT
3664
TAATAAAGTCTAGCCTTACCC

NC_045512.2_21mer_win1_14968
14968
14988
2683
CCATTCCGATCTGAAATAATA
3665
ATAATAAAGTCTAGCCTTACC

NC_045512.2_21mer_win1_14969
14969
14989
2684
CATTCCGATCTGAAATAATAC
3666
CATAATAAAGTCTAGCCTTAC

NC_045512.2_21mer_win1_14970
14970
14990
2685
ATTCCGATCTGAAATAATACT
3667
TCATAATAAAGTCTAGCCTTA

NC_045512.2_21mer_win1_14992
14992
15012
2686
AGTTACTCAATACTCCTAGTT
3668
TTGATCCTCATAACTCATTGA

NC_045512.2_21mer_win1_14993
14993
15013
2687
GTTACTCAATACTCCTAGTTC
3669
CTTGATCCTCATAACTCATTG

NC_045512.2_21mer_win1_14994
14994
15014
2688
TTACTCAATACTCCTAGTTCT
3670
TCTTGATCCTCATAACTCATT

NC_045512.2_21mer_win1_14995
14995
15015
2689
TACTCAATACTCCTAGTTCTA
3671
ATCTTGATCCTCATAACTCAT

NC_045512.2_21mer_win1_14996
14996
15016
2690
ACTCAATACTCCTAGTTCTAC
3672
CATCTTGATCCTCATAACTCA

NC_045512.2_21mer_win1_14997
14997
15017
2691
CTCAATACTCCTAGTTCTACG
3673
GCATCTTGATCCTCATAACTC

NC_045512.2_21mer_win1_14998
14998
15018
2692
TCAATACTCCTAGTTCTACGT
3674
TGCATCTTGATCCTCATAACT

NC_045512.2_21mer_win1_14999
14999
15019
2693
CAATACTCCTAGTTCTACGTG
3675
GTGCATCTTGATCCTCATAAC

NC_045512.2_21mer_win1_15000
15000
15020
2694
AATACTCCTAGTTCTACGTGA
3676
AGTGCATCTTGATCCTCATAA

NC_045512.2_21mer_win1_15055
15055
15075
2695
TATTGAGTTTACTTAGAATTC
3677
CTTAAGATTCATTTGAGTTAT

NC_045512.2_21mer_win1_15056
15056
15076
2696
ATTGAGTTTACTTAGAATTCA
3678
ACTTAAGATTCATTTGAGTTA

NC_045512.2_21mer_win1_15057
15057
15077
2697
TTGAGTTTACTTAGAATTCAT
3679
TACTTAAGATTCATTTGAGTT

NC_045512.2_21mer_win1_15058
15058
15078
2698
TGAGTTTACTTAGAATTCATA
3680
ATACTTAAGATTCATTTGAGT

NC_045512.2_21mer_win1_15059
15059
15079
2699
GAGTTTACTTAGAATTCATAC
3681
CATACTTAAGATTCATTTGAG

NC_045512.2_21mer_win1_15060
15060
15080
2700
AGTTTACTTAGAATTCATACG
3682
GCATACTTAAGATTCATTTGA

NC_045512.2_21mer_win1_15061
15061
15081
2701
GTTTACTTAGAATTCATACGG
3683
GGCATACTTAAGATTCATTTG

NC_045512.2_21mer_win1_15062
15062
15082
2702
TTTACTTAGAATTCATACGGT
3684
TGGCATACTTAAGATTCATTT

NC_045512.2_2lmer_win1_15063
15063
15083
2703
TTACTTAGAATTCATACGGTA
3685
ATGGCATACTTAAGATTCATT

NC_045512.2_2lmer_win1_15064
15064
15084
2704
TACTTAGAATTCATACGGTAA
3686
AATGGCATACTTAAGATTCAT

NC_045512.2_2lmer_win1_15065
15065
15085
2705
ACTTAGAATTCATACGGTAAT
3687
TAATGGCATACTTAAGATTCA

NC_045512.2_2lmer_win1_15066
15066
15086
2706
CTTAGAATTCATACGGTAATC
3688
CTAATGGCATACTTAAGATTC

NC_045512.2_2lmer_win1_15067
15067
15087
2707
TTAGAATTCATACGGTAATCA
3689
ACTAATGGCATACTTAAGATT

NC_045512.2_2lmer_win1_15068
15068
15088
2708
TAGAATTCATACGGTAATCAC
3690
CACTAATGGCATACTTAAGAT

NC_045512.2_2lmer_win1_15069
15069
15089
2709
AGAATTCATACGGTAATCACG
3691
GCACTAATGGCATACTTAAGA

NC_045512.2_2lmer_win1_15070
15070
15090
2710
GAATTCATACGGTAATCACGT
3692
TGCACTAATGGCATACTTAAG

NC_045512.2_2lmer_win1_15071
15071
15091
2711
AATTCATACGGTAATCACGTT
3693
TTGCACTAATGGCATACTTAA

NC_045512.2_2lmer_win1_15072
15072
15092
2712
ATTCATACGGTAATCACGTTT
3694
TTTGCACTAATGGCATACTTA

NC_045512.2_2lmer_win1_15073
15073
15093
2713
TTCATACGGTAATCACGTTTC
3695
CTTTGCACTAATGGCATACTT

NC_045512.2_2lmer_win1_15074
15074
15094
2714
TCATACGGTAATCACGTTTCT
3696
TCTTTGCACTAATGGCATACT

NC_045512.2_2lmer_win1_15075
15075
15095
2715
CATACGGTAATCACGTTTCTT
3697
TTCTTTGCACTAATGGCATAC

NC_045512.2_2lmer_win1_15076
15076
15096
2716
ATACGGTAATCACGTTTCTTA
3698
ATTCTTTGCACTAATGGCATA

NC_045512.2_2lmer_win1_15077
15077
15097
2717
TACGGTAATCACGTTTCTTAT
3699
TATTCTTTGCACTAATGGCAT

NC_045512.2_2lmer_win1_15078
15078
15098
2718
ACGGTAATCACGTTTCTTATC
3700
CTATTCTTTGCACTAATGGCA

NC_045512.2_2lmer_win1_15079
15079
15099
2719
CGGTAATCACGTTTCTTATCT
3701
TCTATTCTTTGCACTAATGGC

NC_045512.2_2lmer_win1_15080
15080
15100
2720
GGTAATCACGTTTCTTATCTC
3702
CTCTATTCTTTGCACTAATGG

NC_045512.2_2lmer_win1_15081
15081
15101
2721
GTAATCACGTTTCTTATCTCG
3703
GCTCTATTCTTTGCACTAATG

NC_045512.2_2lmer_win1_15082
15082
15102
2722
TAATCACGTTTCTTATCTCGA
3704
AGCTCTATTCTTTGCACTAAT

NC_045512.2_2lmer_win1_15083
15083
15103
2723
AATCACGTTTCTTATCTCGAG
3705
GAGCTCTATTCTTTGCACTAA

NC_045512.2_2lmer_win1_15084
15084
15104
2724
ATCACGTTTCTTATCTCGAGC
3706
CGAGCTCTATTCTTTGCACTA

NC_045512.2_2lmer_win1_15085
15085
15105
2725
TCACGTTTCTTATCTCGAGCG
3707
GCGAGCTCTATTCTTTGCACT

NC_045512.2_21mer_win1_15086
15086
15106
2726
CACGTTTCTTATCTCGAGCGT
3708
TGCGAGCTCTATTCTTTGCAC

NC_045512.2_21mer_win1_15087
15087
15107
2727
ACGTTTCTTATCTCGAGCGTG
3709
GTGCGAGCTCTATTCTTTGCA

NC_045512.2_21mer_win1_15088
15088
15108
2728
CGTTTCTTATCTCGAGCGTGG
3710
GGTGCGAGCTCTATTCTTTGC

NC_045512.2_21mer_win1_15089
15089
15109
2729
GTTTCTTATCTCGAGCGTGGC
3711
CGGTGCGAGCTCTATTCTTTG

NC_045512.2_21mer_win1_15090
15090
15110
2730
TTTCTTATCTCGAGCGTGGCA
3712
ACGGTGCGAGCTCTATTCTTT

NC_045512.2_21mer_win1_15091
15091
15111
2731
TTCTTATCTCGAGCGTGGCAT
3713
TACGGTGCGAGCTCTATTCTT

NC_045512.2_21mer_win1_15092
15092
15112
2732
TCTTATCTCGAGCGTGGCATC
3714
CTACGGTGCGAGCTCTATTCT

NC_045512.2_21mer_win1_15093
15093
15113
2733
CTTATCTCGAGCGTGGCATCG
3715
GCTACGGTGCGAGCTCTATTC

NC_045512.2_21mer_win1_15094
15094
15114
2734
TTATCTCGAGCGTGGCATCGA
3716
AGCTACGGTGCGAGCTCTATT

NC_045512.2_21mer_win1_15095
15095
15115
2735
TATCTCGAGCGTGGCATCGAC
3717
CAGCTACGGTGCGAGCTCTAT

NC_045512.2_21mer_win1_15096
15096
15116
2736
ATCTCGAGCGTGGCATCGACC
3718
CCAGCTACGGTGCGAGCTCTA

NC_045512.2_21mer_win1_15097
15097
15117
2737
TCTCGAGCGTGGCATCGACCA
3719
ACCAGCTACGGTGCGAGCTCT

NC_045512.2_21mer_win1_15098
15098
15118
2738
CTCGAGCGTGGCATCGACCAC
3720
CACCAGCTACGGTGCGAGCTC

NC_045512.2_21mer_win1_15099
15099
15119
2739
TCGAGCGTGGCATCGACCACA
3721
ACACCAGCTACGGTGCGAGCT

NC_045512.2_21mer_win1_15100
15100
15120
2740
CGAGCGTGGCATCGACCACAG
3722
GACACCAGCTACGGTGCGAGC

NC_045512.2_21mer_win1_15101
15101
15121
2741
GAGCGTGGCATCGACCACAGA
3723
AGACACCAGCTACGGTGCGAG

NC_045512.2_21mer_win1_15102
15102
15122
2742
AGCGTGGCATCGACCACAGAG
3724
GAGACACCAGCTACGGTGCGA

NC_045512.2_21mer_win1_15103
15103
15123
2743
GCGTGGCATCGACCACAGAGA
3725
AGAGACACCAGCTACGGTGCG

NC_045512.2_21mer_win1_15104
15104
15124
2744
CGTGGCATCGACCACAGAGAT
3726
TAGAGACACCAGCTACGGTGC

NC_045512.2_21mer_win1_15105
15105
15125
2745
GTGGCATCGACCACAGAGATA
3727
ATAGAGACACCAGCTACGGTG

NC_045512.2_21mer_win1_15106
15106
15126
2746
TGGCATCGACCACAGAGATAG
3728
GATAGAGACACCAGCTACGGT

NC_045512.2_21mer_win1_15107
15107
15127
2747
GGCATCGACCACAGAGATAGA
3729
AGATAGAGACACCAGCTACGG

NC_045512.2_21mer_win1_15108
15108
15128
2748
GCATCGACCACAGAGATAGAC
3730
CAGATAGAGACACCAGCTACG

NC_045512.2_2lmer_win1_15109
15109
15129
2749
CATCGACCACAGAGATAGACA
3731
ACAGATAGAGACACCAGCTAC

NC_045512.2_2lmer_win1_15110
15110
15130
2750
ATCGACCACAGAGATAGACAT
3732
TACAGATAGAGACACCAGCTA

NC_045512.2_2lmer_win1_15111
15111
15131
2751
TCGACCACAGAGATAGACATC
3733
CTACAGATAGAGACACCAGCT

NC_045512.2_2lmer_win1_15112
15112
15132
2752
CGACCACAGAGATAGACATCA
3734
ACTACAGATAGAGACACCAGC

NC_045512.2_2lmer_win1_15113
15113
15133
2753
GACCACAGAGATAGACATCAT
3735
TACTACAGATAGAGACACCAG

NC_045512.2_2lmer_win1_15114
15114
15134
2754
ACCACAGAGATAGACATCATG
3736
GTACTACAGATAGAGACACCA

NC_045512.2_2lmer_win1_15115
15115
15135
2755
CCACAGAGATAGACATCATGA
3737
AGTACTACAGATAGAGACACC

NC_045512.2_2lmer_win1_15116
15116
15136
2756
CACAGAGATAGACATCATGAT
3738
TAGTACTACAGATAGAGACAC

NC_045512.2_2lmer_win1_15117
15117
15137
2757
ACAGAGATAGACATCATGATA
3739
ATAGTACTACAGATAGAGACA

NC_045512.2_2lmer_win1_15118
15118
15138
2758
CAGAGATAGACATCATGATAC
3740
CATAGTACTACAGATAGAGAC

NC_045512.2_2lmer_win1_15119
15119
15139
2759
AGAGATAGACATCATGATACT
3741
TCATAGTACTACAGATAGAGA

NC_045512.2_2lmer_win1_15120
15120
15140
2760
GAGATAGACATCATGATACTG
3742
GTCATAGTACTACAGATAGAG

NC_045512.2_2lmer_win1_15172
15172
15192
2761
AGTTATCGGCGGTGATCTCCT
3743
TCCTCTAGTGGCGGCTATTGA

NC_045512.2_2lmer_win1_15173
15173
15193
2762
GTTATCGGCGGTGATCTCCTC
3744
CTCCTCTAGTGGCGGCTATTG

NC_045512.2_2lmer_win1_15174
15174
15194
2763
TTATCGGCGGTGATCTCCTCG
3745
GCTCCTCTAGTGGCGGCTATT

NC_045512.2_2lmer_win1_15175
15175
15195
2764
TATCGGCGGTGATCTCCTCGA
3746
AGCTCCTCTAGTGGCGGCTAT

NC_045512.2_2lmer_win1_15176
15176
15196
2765
ATCGGCGGTGATCTCCTCGAT
3747
TAGCTCCTCTAGTGGCGGCTA

NC_045512.2_2lmer_win1_15177
15177
15197
2766
TCGGCGGTGATCTCCTCGATG
3748
GTAGCTCCTCTAGTGGCGGCT

NC_045512.2_2lmer_win1_15178
15178
15198
2767
CGGCGGTGATCTCCTCGATGA
3749
AGTAGCTCCTCTAGTGGCGGC

NC_045512.2_2lmer_win1_15179
15179
15199
2768
GGCGGTGATCTCCTCGATGAC
3750
CAGTAGCTCCTCTAGTGGCGG

NC_045512.2_2lmer_win1_15180
15180
15200
2769
GCGGTGATCTCCTCGATGACA
3751
ACAGTAGCTCCTCTAGTGGCG

NC_045512.2_2lmer_win1_15310
15310
15330
2770
TCTCGGTACGGATTGTACGAA
3752
AAGCATGTTAGGCATGGCTCT

NC_045512.2_2lmer_win1_15311
15311
15331
2771
CTCGGTACGGATTGTACGAAT
3753
TAAGCATGTTAGGCATGGCTC

NC_045512.2_21mer_win1_15312
15312
15332
2772
TCGGTACGGATTGTACGAATC
3754
CTAAGCATGTTAGGCATGGCT

NC_045512.2_21mer_win1_15346
15346
15366
2773
GAACAAGAACGAGCGTTTGTA
3755
ATGTTTGCGAGCAAGAACAAG

NC_045512.2_21mer_win1_15347
15347
15367
2774
AACAAGAACGAGCGTTTGTAT
3756
TATGTTTGCGAGCAAGAACAA

NC_045512.2_21mer_win1_15496
15496
15516
2775
TGTTGACGAATACGATTATCA
3757
ACTATTAGCATAAGCAGTTGT

NC_045512.2_21mer_win1_15497
15497
15517
2776
GTTGACGAATACGATTATCAC
3758
CACTATTAGCATAAGCAGTTG

NC_045512.2_21mer_win1_15498
15498
15518
2777
TTGACGAATACGATTATCACA
3759
ACACTATTAGCATAAGCAGTT

NC_045512.2_21mer_win1_15622
15622
15642
2778
ATACTCACAGAGATATCTTTA
3760
ATTTCTATAGAGACACTCATA

NC_045512.2_21mer_win1_15623
15623
15643
2779
TACTCACAGAGATATCTTTAT
3761
TATTTCTATAGAGACACTCAT

NC_045512.2_21mer_win1_15624
15624
15644
2780
ACTCACAGAGATATCTTTATC
3762
CTATTTCTATAGAGACACTCA

NC_045512.2_21mer_win1_15838
15838
15858
2781
ACCTGACTCTGACTGGAATGA
3763
AGTAAGGTCAGTCTCAGTCCA

NC_045512.2_21mer_win1_15839
15839
15859
2782
CCTGACTCTGACTGGAATGAT
3764
TAGTAAGGTCAGTCTCAGTCC

NC_045512.2_21mer_win1_15840
15840
15860
2783
CTGACTCTGACTGGAATGATT
3765
TTAGTAAGGTCAGTCTCAGTC

NC_045512.2_21mer_win1_15841
15841
15861
2784
TGACTCTGACTGGAATGATTT
3766
TTTAGTAAGGTCAGTCTCAGT

NC_045512.2_21mer_win1_15842
15842
15862
2785
GACTCTGACTGGAATGATTTC
3767
CTTTAGTAAGGTCAGTCTCAG

NC_045512.2_21mer_win1_15843
15843
15863
2786
ACTCTGACTGGAATGATTTCC
3768
CCTTTAGTAAGGTCAGTCTCA

NC_045512.2_21mer_win1_15844
15844
15864
2787
CTCTGACTGGAATGATTTCCT
3769
TCCTTTAGTAAGGTCAGTCTC

NC_045512.2_21mer_win1_15845
15845
15865
2788
TCTGACTGGAATGATTTCCTG
3770
GTCCTTTAGTAAGGTCAGTCT

NC_045512.2_21mer_win1_15846
15846
15866
2789
CTGACTGGAATGATTTCCTGG
3771
GGTCCTTTAGTAAGGTCAGTC

NC_045512.2_21mer_win1_15847
15847
15867
2790
TGACTGGAATGATTTCCTGGA
3772
AGGTCCTTTAGTAAGGTCAGT

NC_045512.2_21mer_win1_15848
15848
15868
2791
GACTGGAATGATTTCCTGGAG
3773
GAGGTCCTTTAGTAAGGTCAG

NC_045512.2_21mer_win1_15849
15849
15869
2792
ACTGGAATGATTTCCTGGAGT
3774
TGAGGTCCTTTAGTAAGGTCA

NC_045512.2_21mer_win1_15985
15985
16005
2793
TTTTGTCTACCATGTGAATAC
3775
CATAAGTGTACCATCTGTTTT

NC_045512.2_21mer_win1_15986
15986
16006
2794
TTTGTCTACCATGTGAATACT
3776
TCATAAGTGTACCATCTGTTT

NC_045512.2_21mer_win1_15987
15987
16007
2795
TTGTCTACCATGTGAATACTA
3777
ATCATAAGTGTACCATCTGTT

NC_045512.2_21mer_win1_15988
15988
16008
2796
TGTCTACCATGTGAATACTAA
3778
AATCATAAGTGTACCATCTGT

NC_045512.2_21mer_win1_15989
15989
16009
2797
GTCTACCATGTGAATACTAAC
3779
CAATCATAAGTGTACCATCTG

NC_045512.2_21mer_win1_15990
15990
16010
2798
TCTACCATGTGAATACTAACT
3780
TCAATCATAAGTGTACCATCT

NC_045512.2_21mer_win1_16057
16057
16077
2799
GGATTAGTCCTCATACGACTA
3781
ATCAGCATACTCCTGATTAGG

NC_045512.2_21mer_win1_16058
16058
16078
2800
GATTAGTCCTCATACGACTAC
3782
CATCAGCATACTCCTGATTAG

NC_045512.2_21mer_win1_16059
16059
16079
2801
ATTAGTCCTCATACGACTACA
3783
ACATCAGCATACTCCTGATTA

NC_045512.2_21mer_win1_16822
16822
16842
2802
CCTCTCATGTGGAAACTTTTT
3784
TTTTTCAAAGGTGTACTCTCC

NC_045512.2_21mer_win1_16823
16823
16843
2803
CTCTCATGTGGAAACTTTTTC
3785
TTTTTCAAAGGTGTACTCTC

NC_045512.2_21mer_win1_16824
16824
16844
2804
TCTCATGTGGAAACTTTTTCC
3786
CCTTTTTCAAAGGTGTACTCT

NC_045512.2_21mer_win1_16825
16825
16845
2805
CTCATGTGGAAACTTTTTCCA
3787
ACCTTTTTCAAAGGTGTACTC

NC_045512.2_21mer_win1_16826
16826
16846
2806
TCATGTGGAAACTTTTTCCAC
3788
CACCTTTTTCAAAGGTGTACT

NC_045512.2_21mer_win1_16827
16827
16847
2807
CATGTGGAAACTTTTTCCACT
3789
TCACCTTTTTCAAAGGTGTAC

NC_045512.2_21mer_win1_16828
16828
16848
2808
ATGTGGAAACTTTTTCCACTG
3790
GTCACCTTTTTCAAAGGTGTA

NC_045512.2_21mer_win1_16829
16829
16849
2809
TGTGGAAACTTTTTCCACTGA
3791
AGTCACCTTTTTCAAAGGTGT

NC_045512.2_21mer_win1_16830
16830
16850
2810
GTGGAAACTTTTTCCACTGAT
3792
TAGTCACCTTTTTCAAAGGTG

NC_045512.2_21mer_win1_16831
16831
16851
2811
TGGAAACTTTTTCCACTGATA
3793
ATAGTCACCTTTTTCAAAGGT

NC_045512.2_21mer_win1_16832
16832
16852
2812
GGAAACTTTTTCCACTGATAC
3794
CATAGTCACCTTTTTCAAAGG

NC_045512.2_21mer_win1_16833
16833
16853
2813
GAAACTTTTTCCACTGATACC
3795
CCATAGTCACCTTTTTCAAAG

NC_045512.2_21mer_win1_16834
16834
16854
2814
AAACTTTTTCCACTGATACCA
3796
ACCATAGTCACCTTTTTCAAA

NC_045512.2_21mer_win1_16835
16835
16855
2815
AACTTTTTCCACTGATACCAC
3797
CACCATAGTCACCTTTTTCAA

NC_045512.2_21mer_win1_16836
16836
16856
2816
ACTTTTTCCACTGATACCACT
3798
TCACCATAGTCACCTTTTTCA

NC_045512.2_21mer_win1_16837
16837
16857
2817
CTTTTTCCACTGATACCACTA
3799
ATCACCATAGTCACCTTTTTC

NC_045512.2_21mer_win1_16838
16838
16858
2818
TTTTTCCACTGATACCACTAC
3800
CATCACCATAGTCACCTTTTT

NC_045512.2_21mer_win1_16839
16839
16859
2819
TTTTCCACTGATACCACTACG
3801
GCATCACCATAGTCACCTTTT

NC_045512.2_21mer_win1_16840
16840
16860
2820
TTTCCACTGATACCACTACGA
3802
AGCATCACCATAGTCACCTTT

NC_045512.2_21mer_win1_16841
16841
16861
2821
TTCCACTGATACCACTACGAC
3803
CAGCATCACCATAGTCACCTT

NC_045512.2_21mer_win1_16842
16842
16862
2822
TCCACTGATACCACTACGACA
3804
ACAGCATCACCATAGTCACCT

NC_045512.2_21mer_win1_16843
16843
16863
2823
CCACTGATACCACTACGACAA
3805
AACAGCATCACCATAGTCACC

NC_045512.2_21mer_win1_16844
16844
16864
2824
CACTGATACCACTACGACAAC
3806
CAACAGCATCACCATAGTCAC

NC_045512.2_21mer_win1_16845
16845
16865
2825
ACTGATACCACTACGACAACA
3807
ACAACAGCATCACCATAGTCA

NC_045512.2_21mer_win1_16954
16954
16974
2826
GATCACGGTGTTCTCGTGATA
3808
ATAGTGCTCTTGTGGCACTAG

NC_045512.2_21mer_win1_16955
16955
16975
2827
ATCACGGTGTTCTCGTGATAC
3809
CATAGTGCTCTTGTGGCACTA

NC_045512.2_21mer_win1_16956
16956
16976
2828
TCACGGTGTTCTCGTGATACA
3810
ACATAGTGCTCTTGTGGCACT

NC_045512.2_21mer_win1_17008
17008
17028
2829
TAGAGTCTACTCAAAAGATCG
3811
GCTAGAAAACTCATCTGAGAT

NC_045512.2_21mer_win1_17009
17009
17029
2830
AGAGTCTACTCAAAAGATCGT
3812
TGCTAGAAAACTCATCTGAGA

NC_045512.2_21mer_win1_17010
17010
17030
2831
GAGTCTACTCAAAAGATCGTT
3813
TTGCTAGAAAACTCATCTGAG

NC_045512.2_21mer_win1_17011
17011
17031
2832
AGTCTACTCAAAAGATCGTTA
3814
ATTGCTAGAAAACTCATCTGA

NC_045512.2_21mer_win1_17012
17012
17032
2833
GTCTACTCAAAAGATCGTTAC
3815
CATTGCTAGAAAACTCATCTG

NC_045512.2_21mer_win1_17013
17013
17033
2834
TCTACTCAAAAGATCGTTACA
3816
ACATTGCTAGAAAACTCATCT

NC_045512.2_21mer_win1_17014
17014
17034
2835
CTACTCAAAAGATCGTTACAA
3817
AACATTGCTAGAAAACTCATC

NC_045512.2_21mer_win1_17015
17015
17035
2836
TACTCAAAAGATCGTTACAAC
3818
CAACATTGCTAGAAAACTCAT

NC_045512.2_21mer_win1_17016
17016
17036
2837
ACTCAAAAGATCGTTACAACG
3819
GCAACATTGCTAGAAAACTCA

NC_045512.2_21mer_win1_17017
17017
17037
2838
CTCAAAAGATCGTTACAACGT
3820
TGCAACATTGCTAGAAAACTC

NC_045512.2_21mer_win1_17018
17018
17038
2839
TCAAAAGATCGTTACAACGTT
3821
TTGCAACATTGCTAGAAAACT

NC_045512.2_21mer_win1_17019
17019
17039
2840
CAAAAGATCGTTACAACGTTT
3822
TTTGCAACATTGCTAGAAAAC

NC_045512.2_21mer_win1_17020
17020
17040
2841
AAAAGATCGTTACAACGTTTA
3823
ATTTGCAACATTGCTAGAAAA

NC_045512.2_21mer_win1_17021
17021
17041
2842
AAAGATCGTTACAACGTTTAA
3824
AATTTGCAACATTGCTAGAAA

NC_045512.2_21mer_win1_17022
17022
17042
2843
AAGATCGTTACAACGTTTAAT
3825
TAATTTGCAACATTGCTAGAA

NC_045512.2_21mer_win1_17080
17080
17100
2844
CCTGGTGGACCATGACCATTC
3826
CTTACCAGTACCAGGTGGTCC

NC_045512.2_21mer_win1_17081
17081
17101
2845
CTGGTGGACCATGACCATTCT
3827
TCTTACCAGTACCAGGTGGTC

NC_045512.2_21mer_win1_17082
17082
17102
2846
TGGTGGACCATGACCATTCTC
3828
CTCTTACCAGTACCAGGTGGT

NC_045512.2_21mer_win1_17083
17083
17103
2847
GGTGGACCATGACCATTCTCA
3829
ACTCTTACCAGTACCAGGTGG

NC_045512.2_21mer_win1_17084
17084
17104
2848
GTGGACCATGACCATTCTCAG
3830
GACTCTTACCAGTACCAGGTG

NC_045512.2_21mer_win1_17085
17085
17105
2849
TGGACCATGACCATTCTCAGT
3831
TGACTCTTACCAGTACCAGGT

NC_045512.2_21mer_win1_17086
17086
17106
2850
GGACCATGACCATTCTCAGTA
3832
ATGACTCTTACCAGTACCAGG

NC_045512.2_21mer_win1_17087
17087
17107
2851
GACCATGACCATTCTCAGTAA
3833
AATGACTCTTACCAGTACCAG

NC_045512.2_21mer_win1_17088
17088
17108
2852
ACCATGACCATTCTCAGTAAA
3834
AAATGACTCTTACCAGTACCA

NC_045512.2_21mer_win1_17089
17089
17109
2853
CCATGACCATTCTCAGTAAAA
3835
AAAATGACTCTTACCAGTACC

NC_045512.2_21mer_win1_17090
17090
17110
2854
CATGACCATTCTCAGTAAAAC
3836
CAAAATGACTCTTACCAGTAC

NC_045512.2_21mer_win1_17091
17091
17111
2855
ATGACCATTCTCAGTAAAACG
3837
GCAAAATGACTCTTACCAGTA

NC_045512.2_21mer_win1_17269
17269
17289
2856
TTTAAGTTTCACTTAAGTTGT
3838
TGTTGAATTCACTTTGAATTT

NC_045512.2_21mer_win1_18100
18100
18120
2857
TGTGTCCGTGGATGTGTGGAG
3839
GAGGTGTGTAGGTGCCTGTGT

NC_045512.2_21mer_win1_18101
18101
18121
2858
GTGTCCGTGGATGTGTGGAGT
3840
TGAGGTGTGTAGGTGCCTGTG

NC_045512.2_21mer_win1_18102
18102
18122
2859
TGTCCGTGGATGTGTGGAGTC
3841
CTGAGGTGTGTAGGTGCCTGT

NC_045512.2_21mer_win1_18196
18196
18216
2860
TCTGAGTAGAGATACTACCCA
3842
ACCCATCATAGAGATGAGTCT

NC_045512.2_21mer_win1_18197
18197
18217
2861
CTGAGTAGAGATACTACCCAA
3843
AACCCATCATAGAGATGAGTC

NC_045512.2_21mer_win1_18198
18198
18218
2862
TGAGTAGAGATACTACCCAAA
3844
AAACCCATCATAGAGATGAGT

NC_045512.2_21mer_win1_19618
19618
19638
2863
GTCTCAAATCTTTTACACCGA
3845
AGCCACATTTTCTAAACTCTG

NC_045512.2_21mer_win1_19619
19619
19639
2864
TCTCAAATCTTTTACACCGAA
3846
AAGCCACATTTTCTAAACTCT

NC_045512.2_21mer_win1_20107
20107
20127
2865
TTACCTCAGTGTAATTAACCT
3847
TCCAATTAATGTGACTCCATT

NC_045512.2_21mer_win1_20108
20108
20128
2866
TACCTCAGTGTAATTAACCTC
3848
CTCCAATTAATGTGACTCCAT

NC_045512.2_21mer_win1_20109
20109
20129
2867
ACCTCAGTGTAATTAACCTCT
3849
TCTCCAATTAATGTGACTCCA

NC_045512.2_21mer_win1_20110
20110
20130
2868
CCTCAGTGTAATTAACCTCTT
3850
TTCTCCAATTAATGTGACTCC

NC_045512.2_21mer_win1_21502
21502
21522
2869
TAATCTCTTTTGTTGTCTCAA
3851
AACTCTGTTGTTTTCTCTAAT

NC_045512.2_21mer_win1_21503
21503
21523
2870
AATCTCTTTTGTTGTCTCAAC
3852
CAACTCTGTTGTTTTCTCTAA

NC_045512.2_21mer_win1_21504
21504
21524
2871
ATCTCTTTTGTTGTCTCAACA
3853
ACAACTCTGTTGTTTTCTCTA

NC_045512.2_21mer_win1_24302
24302
24322
2872
TTACAAGAGATACTCTTGGTT
3854
TTGGTTCTCATAGAGAACATT

NC_045512.2_21mer_win1_24303
24303
24323
2873
TACAAGAGATACTCTTGGTTT
3855
TTTGGTTCTCATAGAGAACAT

NC_045512.2_21mer_win1_24304
24304
24324
2874
ACAAGAGATACTCTTGGTTTT
3856
TTTTGGTTCTCATAGAGAACA

NC_045512.2_21mer_win1_24305
24305
24325
2875
CAAGAGATACTCTTGGTTTTT
3857
TTTTTGGTTCTCATAGAGAAC

NC_045512.2_21mer_win1_24620
24620
24640
2876
CGAAGACGATTAGAACGACGA
3858
AGCAGCAAGATTAGCAGAAGC

NC_045512.2_21mer_win1_24621
24621
24641
2877
GAAGACGATTAGAACGACGAT
3859
TAGCAGCAAGATTAGCAGAAG

NC_045512.2_21mer_win1_24622
24622
24642
2878
AAGACGATTAGAACGACGATG
3860
GTAGCAGCAAGATTAGCAGAA

NC_045512.2_21mer_win1_24623
24623
24643
2879
AGACGATTAGAACGACGATGA
3861
AGTAGCAGCAAGATTAGCAGA

NC_045512.2_21mer_win1_24624
24624
24644
2880
GACGATTAGAACGACGATGAT
3862
TAGTAGCAGCAAGATTAGCAG

NC_045512.2_21mer_win1_24625
24625
24645
2881
ACGATTAGAACGACGATGATT
3863
TTAGTAGCAGCAAGATTAGCA

NC_045512.2_21mer_win1_24626
24626
24646
2882
CGATTAGAACGACGATGATTT
3864
TTTAGTAGCAGCAAGATTAGC

NC_045512.2_21mer_win1_24627
24627
24647
2883
GATTAGAACGACGATGATTTT
3865
TTTTAGTAGCAGCAAGATTAG

NC_045512.2_21mer_win1_24628
24628
24648
2884
ATTAGAACGACGATGATTTTA
3866
ATTTTAGTAGCAGCAAGATTA

NC_045512.2_21mer_win1_24629
24629
24649
2885
TTAGAACGACGATGATTTTAC
3867
CATTTTAGTAGCAGCAAGATT

NC_045512.2_21mer_win1_24630
24630
24650
2886
TAGAACGACGATGATTTTACA
3868
ACATTTTAGTAGCAGCAAGAT

NC_045512.2_21mer_win1_24631
24631
24651
2887
AGAACGACGATGATTTTACAG
3869
GACATTTTAGTAGCAGCAAGA

NC_045512.2_21mer_win1_24662
24662
24682
2888
GAACCTGTTAGTTTTTCTCAA
3870
AACTCTTTTTGATTGTCCAAG

NC_045512.2_21mer_win1_24663
24663
24683
2889
AACCTGTTAGTTTTTCTCAAC
3871
CAACTCTTTTTGATTGTCCAA

NC_045512.2_21mer_win1_24664
24664
24684
2890
ACCTGTTAGTTTTTCTCAACT
3872
TCAACTCTTTTTGATTGTCCA

NC_045512.2_21mer_win1_25034
25034
25054
2891
TTAGTATGTAGTGGTCTACAA
3873
AACATCTGGTGATGTATGATT

NC_045512.2_2lmer_win1_25035
25035
25055
2892
TAGTATGTAGTGGTCTACAAC
3874
CAACATCTGGTGATGTATGAT

NC_045512.2_21mer_win1_25036
25036
25056
2893
AGTATGTAGTGGTCTACAACT
3875
TCAACATCTGGTGATGTATGA

NC_045512.2_21mer_win1_25037
25037
25057
2894
GTATGTAGTGGTCTACAACTA
3876
ATCAACATCTGGTGATGTATG

NC_045512.2_2lmer_win1_25104
25104
25124
2895
TTCTTTAACTGGCGGAGTTAC
3877
CATTGAGGCGGTCAATTTCTT

NC_045512.2_2lmer_win1_25105
25105
25125
2896
TCTTTAACTGGCGGAGTTACT
3878
TCATTGAGGCGGTCAATTTCT

NC_045512.2_2lmer_win1_25106
25106
25126
2897
CTTTAACTGGCGGAGTTACTC
3879
CTCATTGAGGCGGTCAATTTC

NC_045512.2_2lmer_win1_25107
25107
25127
2898
TTTAACTGGCGGAGTTACTCC
3880
CCTCATTGAGGCGGTCAATTT

NC_045512.2_2lmer_win1_25108
25108
25128
2899
TTAACTGGCGGAGTTACTCCA
3881
ACCTCATTGAGGCGGTCAATT

NC_045512.2_21mer_win1_25364
25364
25384
2900
CAGTTTAATGTAATGTGTATT
3882
TTATGTGTAATGTAATTTGAC

NC_045512.2_21mer_win1_25365
25365
25385
2901
AGTTTAATGTAATGTGTATTT
3883
TTTATGTGTAATGTAATTTGA

NC_045512.2_21mer_win1_25366
25366
25386
2902
GTTTAATGTAATGTGTATTTG
3884
GTTTATGTGTAATGTAATTTG

NC_045512.2_21mer_win1_25367
25367
25387
2903
TTTAATGTAATGTGTATTTGC
3885
CGTTTATGTGTAATGTAATTT

NC_045512.2_21mer_win1_25502
25502
25522
2904
ATGTTCGGAGTGAGGGAAAGC
3886
CGAAAGGGAGTGAGGCTTGTA

NC_045512.2_21mer_win1_25503
25503
25523
2905
TGTTCGGAGTGAGGGAAAGCC
3887
CCGAAAGGGAGTGAGGCTTGT

NC_045512.2_21mer_win1_25504
25504
25524
2906
GTTCGGAGTGAGGGAAAGCCT
3888
TCCGAAAGGGAGTGAGGCTTG

NC_045512.2_21mer_win1_25505
25505
25525
2907
TTCGGAGTGAGGGAAAGCCTA
3889
ATCCGAAAGGGAGTGAGGCTT

NC_045512.2_21mer_win1_25506
25506
25526
2908
TCGGAGTGAGGGAAAGCCTAC
3890
CATCCGAAAGGGAGTGAGGCT

NC_045512.2_21mer_win1_25507
25507
25527
2909
CGGAGTGAGGGAAAGCCTACC
3891
CCATCCGAAAGGGAGTGAGGC

NC_045512.2_21mer_win1_25508
25508
25528
2910
GGAGTGAGGGAAAGCCTACCG
3892
GCCATCCGAAAGGGAGTGAGG

NC_045512.2_21mer_win1_25509
25509
25529
2911
GAGTGAGGGAAAGCCTACCGA
3893
AGCCATCCGAAAGGGAGTGAG

NC_045512.2_21mer_win1_25510
25510
25530
2912
AGTGAGGGAAAGCCTACCGAA
3894
AAGCCATCCGAAAGGGAGTGA

NC_045512.2_21mer_win1_26191
26191
26211
2913
GGCTGCTGCTGATGATCGCAC
3895
CACGCTAGTAGTCGTCGTCGG

NC_045512.2_21mer_win1_26192
26192
26212
2914
GCTGCTGCTGATGATCGCACG
3896
GCACGCTAGTAGTCGTCGTCG

NC_045512.2_21mer_win1_26193
26193
26213
2915
CTGCTGCTGATGATCGCACGG
3897
GGCACGCTAGTAGTCGTCGTC

NC_045512.2_21mer_win1_26194
26194
26214
2916
TGCTGCTGATGATCGCACGGA
3898
AGGCACGCTAGTAGTCGTCGT

NC_045512.2_21mer_win1_26195
26195
26215
2917
GCTGCTGATGATCGCACGGAA
3899
AAGGCACGCTAGTAGTCGTCG

NC_045512.2_21mer_win1_26196
26196
26216
2918
CTGCTGATGATCGCACGGAAA
3900
AAAGGCACGCTAGTAGTCGTC

NC_045512.2_21mer_win1_26197
26197
26217
2919
TGCTGATGATCGCACGGAAAC
3901
CAAAGGCACGCTAGTAGTCGT

NC_045512.2_21mer_win1_26198
26198
26218
2920
GCTGATGATCGCACGGAAACA
3902
ACAAAGGCACGCTAGTAGTCG

NC_045512.2_21mer_win1_26199
26199
26219
2921
CTGATGATCGCACGGAAACAT
3903
TACAAAGGCACGCTAGTAGTC

NC_045512.2_21mer_win1_26200
26200
26220
2922
TGATGATCGCACGGAAACATT
3904
TTACAAAGGCACGCTAGTAGT

NC_045512.2_21mer_win1_26201
26201
26221
2923
GATGATCGCACGGAAACATTC
3905
CTTACAAAGGCACGCTAGTAG

NC_045512.2_21mer_win1_26202
26202
26222
2924
ATGATCGCACGGAAACATTCG
3906
GCTTACAAAGGCACGCTAGTA

NC_045512.2_21mer_win1_26203
26203
26223
2925
TGATCGCACGGAAACATTCGT
3907
TGCTTACAAAGGCACGCTAGT

NC_045512.2_21mer_win1_26204
26204
26224
2926
GATCGCACGGAAACATTCGTG
3908
GTGCTTACAAAGGCACGCTAG

NC_045512.2_21mer_win1_26205
26205
26225
2927
ATCGCACGGAAACATTCGTGT
3909
TGTGCTTACAAAGGCACGCTA

NC_045512.2_21mer_win1_26206
26206
26226
2928
TCGCACGGAAACATTCGTGTT
3910
TTGTGCTTACAAAGGCACGCT

NC_045512.2_21mer_win1_26207
26207
26227
2929
CGCACGGAAACATTCGTGTTC
3911
CTTGTGCTTACAAAGGCACGC

NC_045512.2_21mer_win1_26232
26232
26252
2930
ACTCATGCTTGAATACATGAG
3912
GAGTACATAAGTTCGTACTCA

NC_045512.2_21mer_win1_26233
26233
26253
2931
CTCATGCTTGAATACATGAGT
3913
TGAGTACATAAGTTCGTACTC

NC_045512.2_21mer_win1_26234
26234
26254
2932
TCATGCTTGAATACATGAGTA
3914
ATGAGTACATAAGTTCGTACT

NC_045512.2_21mer_win1_26235
26235
26255
2933
CATGCTTGAATACATGAGTAA
3915
AATGAGTACATAAGTTCGTAC

NC_045512.2_21mer_win1_26236
26236
26256
2934
ATGCTTGAATACATGAGTAAG
3916
GAATGAGTACATAAGTTCGTA

NC_045512.2_21mer_win1_26237
26237
26257
2935
TGCTTGAATACATGAGTAAGC
3917
CGAATGAGTACATAAGTTCGT

NC_045512.2_21mer_win1_26238
26238
26258
2936
GCTTGAATACATGAGTAAGCA
3918
ACGAATGAGTACATAAGTTCG

NC_045512.2_21mer_win1_26239
26239
26259
2937
CTTGAATACATGAGTAAGCAA
3919
AACGAATGAGTACATAAGTTC

NC_045512.2_21mer_win1_26240
26240
26260
2938
TTGAATACATGAGTAAGCAAA
3920
AAACGAATGAGTACATAAGTT

NC_045512.2_21mer_win1_26241
26241
26261
2939
TGAATACATGAGTAAGCAAAG
3921
GAAACGAATGAGTACATAAGT

NC_045512.2_21mer_win1_26242
26242
26262
2940
GAATACATGAGTAAGCAAAGC
3922
CGAAACGAATGAGTACATAAG

NC_045512.2_21mer_win1_26243
26243
26263
2941
AATACATGAGTAAGCAAAGCC
3923
CCGAAACGAATGAGTACATAA

NC_045512.2_21mer_win1_26244
26244
26264
2942
ATACATGAGTAAGCAAAGCCT
3924
TCCGAAACGAATGAGTACATA

NC_045512.2_21mer_win1_26245
26245
26265
2943
TACATGAGTAAGCAAAGCCTT
3925
TTCCGAAACGAATGAGTACAT

NC_045512.2_21mer_win1_26246
26246
26266
2944
ACATGAGTAAGCAAAGCCTTC
3926
CTTCCGAAACGAATGAGTACA

NC_045512.2_21mer_win1_26247
26247
26267
2945
CATGAGTAAGCAAAGCCTTCT
3927
TCTTCCGAAACGAATGAGTAC

NC_045512.2_21mer_win1_26269
26269
26289
2946
TGTCCATGCAATTATCAATTA
3928
ATTAACTATTAACGTACCTGT

NC_045512.2_21mer_win1_26270
26270
26290
2947
GTCCATGCAATTATCAATTAT
3929
TATTAACTATTAACGTACCTG

NC_045512.2_21mer_win1_26271
26271
26291
2948
TCCATGCAATTATCAATTATC
3930
CTATTAACTATTAACGTACCT

NC_045512.2_21mer_win1_26272
26272
26292
2949
CCATGCAATTATCAATTATCG
3931
GCTATTAACTATTAACGTACC

NC_045512.2_21mer_win1_26273
26273
26293
2950
CATGCAATTATCAATTATCGC
3932
CGCTATTAACTATTAACGTAC

NC_045512.2_21mer_win1_26274
26274
26294
2951
ATGCAATTATCAATTATCGCA
3933
ACGCTATTAACTATTAACGTA

NC_045512.2_21mer_win1_26275
26275
26295
2952
TGCAATTATCAATTATCGCAT
3934
TACGCTATTAACTATTAACGT

NC_045512.2_21mer_win1_26276
26276
26296
2953
GCAATTATCAATTATCGCATG
3935
GTACGCTATTAACTATTAACG

NC_045512.2_21mer_win1_26277
26277
26297
2954
CAATTATCAATTATCGCATGA
3936
AGTACGCTATTAACTATTAAC

NC_045512.2_21mer_win1_26278
26278
26298
2955
AATTATCAATTATCGCATGAA
3937
AAGTACGCTATTAACTATTAA

NC_045512.2_21mer_win1_26279
26279
26299
2956
ATTATCAATTATCGCATGAAG
3938
GAAGTACGCTATTAACTATTA

NC_045512.2_21mer_win1_26280
26280
26300
2957
TTATCAATTATCGCATGAAGA
3939
AGAAGTACGCTATTAACTATT

NC_045512.2_21mer_win1_26281
26281
26301
2958
TATCAATTATCGCATGAAGAA
3940
AAGAAGTACGCTATTAACTAT

NC_045512.2_21mer_win1_26282
26282
26302
2959
ATCAATTATCGCATGAAGAAA
3941
AAAGAAGTACGCTATTAACTA

NC_045512.2_21mer_win1_26283
26283
26303
2960
TCAATTATCGCATGAAGAAAA
3942
AAAAGAAGTACGCTATTAACT

NC_045512.2_21mer_win1_26284
26284
26304
2961
CAATTATCGCATGAAGAAAAA
3943
AAAAAGAAGTACGCTATTAAC

NC_045512.2_21mer_win1_26285
26285
26305
2962
AATTATCGCATGAAGAAAAAG
3944
GAAAAAGAAGTACGCTATTAA

NC_045512.2_21mer_win1_26286
26286
26306
2963
ATTATCGCATGAAGAAAAAGA
3945
AGAAAAAGAAGTACGCTATTA

NC_045512.2_21mer_win1_26287
26287
26307
2964
TTATCGCATGAAGAAAAAGAA
3946
AAGAAAAAGAAGTACGCTATT

NC_045512.2_21mer_win1_26288
26288
26308
2965
TATCGCATGAAGAAAAAGAAC
3947
CAAGAAAAAGAAGTACGCTAT

NC_045512.2_21mer_win1_26289
26289
26309
2966
ATCGCATGAAGAAAAAGAACG
3948
GCAAGAAAAAGAAGTACGCTA

NC_045512.2_21mer_win1_26290
26290
26310
2967
TCGCATGAAGAAAAAGAACGA
3949
AGCAAGAAAAAGAAGTACGCT

NC_045512.2_21mer_win1_26291
26291
26311
2968
CGCATGAAGAAAAAGAACGAA
3950
AAGCAAGAAAAAGAAGTACGC

NC_045512.2_21mer_win1_26292
26292
26312
2969
GCATGAAGAAAAAGAACGAAA
3951
AAAGCAAGAAAAAGAAGTACG

NC_045512.2_21mer_win1_26293
26293
26313
2970
CATGAAGAAAAAGAACGAAAG
3952
GAAAGCAAGAAAAAGAAGTAC

NC_045512.2_21mer_win1_26294
26294
26314
2971
ATGAAGAAAAAGAACGAAAGC
3953
CGAAAGCAAGAAAAAGAAGTA

NC_045512.2_21mer_win1_26295
26295
26315
2972
TGAAGAAAAAGAACGAAAGCA
3954
ACGAAAGCAAGAAAAAGAAGT

NC_045512.2_21mer_win1_26296
26296
26316
2973
GAAGAAAAAGAACGAAAGCAC
3955
CACGAAAGCAAGAAAAAGAAG

NC_045512.2_21mer_win1_26297
26297
26317
2974
AAGAAAAAGAACGAAAGCACC
3956
CCACGAAAGCAAGAAAAAGAA

NC_045512.2_21mer_win1_26298
26298
26318
2975
AGAAAAAGAACGAAAGCACCA
3957
ACCACGAAAGCAAGAAAAAGA

NC_045512.2_21mer_win1_26299
26299
26319
2976
GAAAAAGAACGAAAGCACCAT
3958
TACCACGAAAGCAAGAAAAAG

NC_045512.2_21mer_win1_26300
26300
26320
2977
AAAAAGAACGAAAGCACCATA
3959
ATACCACGAAAGCAAGAAAAA

NC_045512.2_21mer_win1_26301
26301
26321
2978
AAAAGAACGAAAGCACCATAA
3960
AATACCACGAAAGCAAGAAAA

NC_045512.2_21mer_win1_26302
26302
26322
2979
AAAGAACGAAAGCACCATAAG
3961
GAATACCACGAAAGCAAGAAA

NC_045512.2_21mer_win1_26303
26303
26323
2980
AAGAACGAAAGCACCATAAGA
3962
AGAATACCACGAAAGCAAGAA

NC_045512.2_21mer_win1_26304
26304
26324
2981
AGAACGAAAGCACCATAAGAA
3963
AAGAATACCACGAAAGCAAGA

NC_045512.2_21mer_win1_26305
26305
26325
2982
GAACGAAAGCACCATAAGAAC
3964
CAAGAATACCACGAAAGCAAG

NC_045512.2_21mer_win1_26306
26306
26326
2983
AACGAAAGCACCATAAGAACG
3965
GCAAGAATACCACGAAAGCAA

NC_045512.2_21mer_win1_26307
26307
26327
2984
ACGAAAGCACCATAAGAACGA
3966
AGCAAGAATACCACGAAAGCA

NC_045512.2_21mer_win1_26308
26308
26328
2985
CGAAAGCACCATAAGAACGAT
3967
TAGCAAGAATACCACGAAAGC

NC_045512.2_21mer_win1_26309
26309
26329
2986
GAAAGCACCATAAGAACGATC
3968
CTAGCAAGAATACCACGAAAG

NC_045512.2_21mer_win1_26310
26310
26330
2987
AAAGCACCATAAGAACGATCA
3969
ACTAGCAAGAATACCACGAAA

NC_045512.2_21mer_win1_26332
26332
26352
2988
TGTGATCGGTAGGAATGACGC
3970
CGCAGTAAGGATGGCTAGTGT

NC_045512.2_21mer_win1_26333
26333
26353
2989
GTGATCGGTAGGAATGACGCG
3971
GCGCAGTAAGGATGGCTAGTG

NC_045512.2_21mer_win1_26334
26334
26354
2990
TGATCGGTAGGAATGACGCGA
3972
AGCGCAGTAAGGATGGCTAGT

NC_045512.2_21mer_win1_26335
26335
26355
2991
GATCGGTAGGAATGACGCGAA
3973
AAGCGCAGTAAGGATGGCTAG

NC_045512.2_21mer_win1_26336
26336
26356
2992
ATCGGTAGGAATGACGCGAAG
3974
GAAGCGCAGTAAGGATGGCTA

NC_045512.2_21mer_win1_26337
26337
26357
2993
TCGGTAGGAATGACGCGAAGC
3975
CGAAGCGCAGTAAGGATGGCT

NC_045512.2_21mer_win1_26338
26338
26358
2994
CGGTAGGAATGACGCGAAGCT
3976
TCGAAGCGCAGTAAGGATGGC

NC_045512.2_21mer_win1_26339
26339
26359
2995
GGTAGGAATGACGCGAAGCTA
3977
ATCGAAGCGCAGTAAGGATGG

NC_045512.2_21mer_win1_26340
26340
26360
2996
GTAGGAATGACGCGAAGCTAA
3978
AATCGAAGCGCAGTAAGGATG

NC_045512.2_21mer_win1_26341
26341
26361
2997
TAGGAATGACGCGAAGCTAAC
3979
CAATCGAAGCGCAGTAAGGAT

NC_045512.2_21mer_win1_26342
26342
26362
2998
AGGAATGACGCGAAGCTAACA
3980
ACAATCGAAGCGCAGTAAGGA

NC_045512.2_21mer_win1_26343
26343
26363
2999
GGAATGACGCGAAGCTAACAC
3981
CACAATCGAAGCGCAGTAAGG

NC_045512.2_21mer_win1_26344
26344
26364
3000
GAATGACGCGAAGCTAACACA
3982
ACACAATCGAAGCGCAGTAAG

NC_045512.2_21mer_win1_26345
26345
26365
3001
AATGACGCGAAGCTAACACAC
3983
CACACAATCGAAGCGCAGTAA

NC_045512.2_21mer_win1_26346
26346
26366
3002
ATGACGCGAAGCTAACACACG
3984
GCACACAATCGAAGCGCAGTA

NC_045512.2_21mer_win1_26347
26347
26367
3003
TGACGCGAAGCTAACACACGC
3985
CGCACACAATCGAAGCGCAGT

NC_045512.2_21mer_win1_26348
26348
26368
3004
GACGCGAAGCTAACACACGCA
3986
ACGCACACAATCGAAGCGCAG

NC_045512.2_21mer_win1_26349
26349
26369
3005
ACGCGAAGCTAACACACGCAT
3987
TACGCACACAATCGAAGCGCA

NC_045512.2_21mer_win1_26350
26350
26370
3006
CGCGAAGCTAACACACGCATG
3988
GTACGCACACAATCGAAGCGC

NC_045512.2_21mer_win1_26351
26351
26371
3007
GCGAAGCTAACACACGCATGA
3989
AGTACGCACACAATCGAAGCG

NC_045512.2_21mer_win1_26352
26352
26372
3008
CGAAGCTAACACACGCATGAC
3990
CAGTACGCACACAATCGAAGC

NC_045512.2_21mer_win1_26353
26353
26373
3009
GAAGCTAACACACGCATGACG
3991
GCAGTACGCACACAATCGAAG

NC_045512.2_21mer_win1_26354
26354
26374
3010
AAGCTAACACACGCATGACGA
3992
AGCAGTACGCACACAATCGAA

NC_045512.2_21mer_win1_26355
26355
26375
3011
AGCTAACACACGCATGACGAC
3993
CAGCAGTACGCACACAATCGA

NC_045512.2_21mer_win1_26356
26356
26376
3012
GCTAACACACGCATGACGACG
3994
GCAGCAGTACGCACACAATCG

NC_045512.2_21mer_win1_26357
26357
26377
3013
CTAACACACGCATGACGACGT
3995
TGCAGCAGTACGCACACAATC

NC_045512.2_21mer_win1_26358
26358
26378
3014
TAACACACGCATGACGACGTT
3996
TTGCAGCAGTACGCACACAAT

NC_045512.2_21mer_win1_26359
26359
26379
3015
AACACACGCATGACGACGTTA
3997
ATTGCAGCAGTACGCACACAA

NC_045512.2_21mer_win1_26360
26360
26380
3016
ACACACGCATGACGACGTTAT
3998
TATTGCAGCAGTACGCACACA

NC_045512.2_21mer_win1_26361
26361
26381
3017
CACACGCATGACGACGTTATA
3999
ATATTGCAGCAGTACGCACAC

NC_045512.2_21mer_win1_26362
26362
26382
3018
ACACGCATGACGACGTTATAA
4000
AATATTGCAGCAGTACGCACA

NC_045512.2_21mer_win1_26363
26363
26383
3019
CACGCATGACGACGTTATAAC
4001
CAATATTGCAGCAGTACGCAC

NC_045512.2_21mer_win1_26364
26364
26384
3020
ACGCATGACGACGTTATAACA
4002
ACAATATTGCAGCAGTACGCA

NC_045512.2_21mer_win1_26365
26365
26385
3021
CGCATGACGACGTTATAACAA
4003
AACAATATTGCAGCAGTACGC

NC_045512.2_21mer_win1_26366
26366
26386
3022
GCATGACGACGTTATAACAAT
4004
TAACAATATTGCAGCAGTACG

NC_045512.2_21mer_win1_26367
26367
26387
3023
CATGACGACGTTATAACAATT
4005
TTAACAATATTGCAGCAGTAC

NC_045512.2_21mer_win1_26368
26368
26388
3024
ATGACGACGTTATAACAATTG
4006
GTTAACAATATTGCAGCAGTA

NC_045512.2_21mer_win1_26369
26369
26389
3025
TGACGACGTTATAACAATTGC
4007
CGTTAACAATATTGCAGCAGT

NC_045512.2_21mer_win1_26370
26370
26390
3026
GACGACGTTATAACAATTGCA
4008
ACGTTAACAATATTGCAGCAG

NC_045512.2_21mer_win1_26371
26371
26391
3027
ACGACGTTATAACAATTGCAC
4009
CACGTTAACAATATTGCAGCA

NC_045512.2_21mer_win1_26372
26372
26392
3028
CGACGTTATAACAATTGCACT
4010
TCACGTTAACAATATTGCAGC

NC_045512.2_21mer_win1_26373
26373
26393
3029
GACGTTATAACAATTGCACTC
4011
CTCACGTTAACAATATTGCAG

NC_045512.2_21mer_win1_26374
26374
26394
3030
ACGTTATAACAATTGCACTCA
4012
ACTCACGTTAACAATATTGCA

NC_045512.2_21mer_win1_26450
26450
26470
3031
CTCAAGGACTAGAAGACCAGA
4013
AGACCAGAAGATCAGGAACTC

NC_045512.2_21mer_win1_26451
26451
26471
3032
TCAAGGACTAGAAGACCAGAT
4014
TAGACCAGAAGATCAGGAACT

NC_045512.2_21mer_win1_26452
26452
26472
3033
CAAGGACTAGAAGACCAGATT
4015
TTAGACCAGAAGATCAGGAAC

NC_045512.2_21mer_win1_26453
26453
26473
3034
AAGGACTAGAAGACCAGATTT
4016
TTTAGACCAGAAGATCAGGAA

NC_045512.2_21mer_win1_26454
26454
26474
3035
AGGACTAGAAGACCAGATTTG
4017
GTTTAGACCAGAAGATCAGGA

NC_045512.2_21mer_win1_26455
26455
26475
3036
GGACTAGAAGACCAGATTTGC
4018
CGTTTAGACCAGAAGATCAGG

NC_045512.2_21mer_win1_26456
26456
26476
3037
GACTAGAAGACCAGATTTGCT
4019
TCGTTTAGACCAGAAGATCAG

NC_045512.2_21mer_win1_26457
26457
26477
3038
ACTAGAAGACCAGATTTGCTT
4020
TTCGTTTAGACCAGAAGATCA

NC_045512.2_21mer_win1_26458
26458
26478
3039
CTAGAAGACCAGATTTGCTTG
4021
GTTCGTTTAGACCAGAAGATC

NC_045512.2_21mer_win1_26459
26459
26479
3040
TAGAAGACCAGATTTGCTTGA
4022
AGTTCGTTTAGACCAGAAGAT

NC_045512.2_21mer_win1_26460
26460
26480
3041
AGAAGACCAGATTTGCTTGAT
4023
TAGTTCGTTTAGACCAGAAGA

NC_045512.2_21mer_win1_26461
26461
26481
3042
GAAGACCAGATTTGCTTGATT
4024
TTAGTTCGTTTAGACCAGAAG

NC_045512.2_21mer_win1_26574
26574
26594
3043
CTTGTTACCTTGGATCATTAT
4025
TATTACTAGGTTCCATTGTTC

NC_045512.2_21mer_win1_26575
26575
26595
3044
TTGTTACCTTGGATCATTATC
4026
CTATTACTAGGTTCCATTGTT

NC_045512.2_21mer_win1_26576
26576
26596
3045
TGTTACCTTGGATCATTATCC
4027
CCTATTACTAGGTTCCATTGT

NC_045512.2_21mer_win1_26577
26577
26597
3046
GTTACCTTGGATCATTATCCA
4028
ACCTATTACTAGGTTCCATTG

NC_045512.2_21mer_win1_26578
26578
26598
3047
TTACCTTGGATCATTATCCAA
4029
AACCTATTACTAGGTTCCATT

NC_045512.2_21mer_win1_26579
26579
26599
3048
TACCTTGGATCATTATCCAAA
4030
AAACCTATTACTAGGTTCCAT

NC_045512.2_21mer_win1_26580
26580
26600
3049
ACCTTGGATCATTATCCAAAG
4031
GAAACCTATTACTAGGTTCCA

NC_045512.2_21mer_win1_27033
27033
27053
3050
CGATGTAGTGCTTGCGAAAGA
4032
AGAAAGCGTTCGTGATGTAGC

NC_045512.2_21mer_win1_27034
27034
27054
3051
GATGTAGTGCTTGCGAAAGAA
4033
AAGAAAGCGTTCGTGATGTAG

NC_045512.2_21mer_win1_27035
27035
27055
3052
ATGTAGTGCTTGCGAAAGAAT
4034
TAAGAAAGCGTTCGTGATGTA

NC_045512.2_21mer_win1_27036
27036
27056
3053
TGTAGTGCTTGCGAAAGAATA
4035
ATAAGAAAGCGTTCGTGATGT

NC_045512.2_21mer_win1_27037
27037
27057
3054
GTAGTGCTTGCGAAAGAATAA
4036
AATAAGAAAGCGTTCGTGATG

NC_045512.2_21mer_win1_27038
27038
27058
3055
TAGTGCTTGCGAAAGAATAAT
4037
TAATAAGAAAGCGTTCGTGAT

NC_045512.2_21mer_win1_27039
27039
27059
3056
AGTGCTTGCGAAAGAATAATG
4038
GTAATAAGAAAGCGTTCGTGA

NC_045512.2_21mer_win1_27040
27040
27060
3057
GTGCTTGCGAAAGAATAATGT
4039
TGTAATAAGAAAGCGTTCGTG

NC_045512.2_21mer_win1_27041
27041
27061
3058
TGCTTGCGAAAGAATAATGTT
4040
TTGTAATAAGAAAGCGTTCGT

NC_045512.2_21mer_win1_27042
27042
27062
3059
GCTTGCGAAAGAATAATGTTT
4041
TTTGTAATAAGAAAGCGTTCG

NC_045512.2_21mer_win1_27043
27043
27063
3060
CTTGCGAAAGAATAATGTTTA
4042
ATTTGTAATAAGAAAGCGTTC

NC_045512.2_21mer_win1_27044
27044
27064
3061
TTGCGAAAGAATAATGTTTAA
4043
AATTTGTAATAAGAAAGCGTT

NC_045512.2_21mer_win1_27183
27183
27203
3062
CATGTCATTCACTGTTGTCTA
4044
ATCTGTTGTCACTTACTGTAC

NC_045512.2_21mer_win1_27184
27184
27204
3063
ATGTCATTCACTGTTGTCTAC
4045
CATCTGTTGTCACTTACTGTA

NC_045512.2_21mer_win1_27185
27185
27205
3064
TGTCATTCACTGTTGTCTACA
4046
ACATCTGTTGTCACTTACTGT

NC_045512.2_21mer_win1_27186
27186
27206
3065
GTCATTCACTGTTGTCTACAA
4047
AACATCTGTTGTCACTTACTG

NC_045512.2_21mer_win1_27187
27187
27207
3066
TCATTCACTGTTGTCTACAAA
4048
AAACATCTGTTGTCACTTACT

NC_045512.2_21mer_win1_27188
27188
27208
3067
CATTCACTGTTGTCTACAAAG
4049
GAAACATCTGTTGTCACTTAC

NC_045512.2_21mer_win1_27189
27189
27209
3068
ATTCACTGTTGTCTACAAAGT
4050
TGAAACATCTGTTGTCACTTA

NC_045512.2_21mer_win1_27190
27190
27210
3069
TTCACTGTTGTCTACAAAGTA
4051
ATGAAACATCTGTTGTCACTT

NC_045512.2_21mer_win1_27191
27191
27211
3070
TCACTGTTGTCTACAAAGTAG
4052
GATGAAACATCTGTTGTCACT

NC_045512.2_21mer_win1_27192
27192
27212
3071
CACTGTTGTCTACAAAGTAGA
4053
AGATGAAACATCTGTTGTCAC

NC_045512.2_21mer_win1_27382
27382
27402
3072
CTAATTTGCTTGTACTTTTAA
4054
AATTTTCATGTTCGTTTAATC

NC_045512.2_21mer_win1_27383
27383
27403
3073
TAATTTGCTTGTACTTTTAAT
4055
TAATTTTCATGTTCGTTTAAT

NC_045512.2_21mer_win1_27384
27384
27404
3074
AATTTGCTTGTACTTTTAATA
4056
ATAATTTTCATGTTCGTTTAA

NC_045512.2_21mer_win1_27385
27385
27405
3075
ATTTGCTTGTACTTTTAATAA
4057
AATAATTTTCATGTTCGTTTA

NC_045512.2_21mer_win1_27386
27386
27406
3076
TTTGCTTGTACTTTTAATAAG
4058
GAATAATTTTCATGTTCGTTT

NC_045512.2_21mer_win1_27387
27387
27407
3077
TTGCTTGTACTTTTAATAAGA
4059
AGAATAATTTTCATGTTCGTT

NC_045512.2_21mer_win1_27511
27511
27531
3078
ATGCTCCCGTTAAGTGGTAAA
4060
AAATGGTGAATTGCCCTCGTA

NC_045512.2_21mer_win1_27512
27512
27532
3079
TGCTCCCGTTAAGTGGTAAAG
4061
GAAATGGTGAATTGCCCTCGT

NC_045512.2_21mer_win1_27513
27513
27533
3080
GCTCCCGTTAAGTGGTAAAGT
4062
TGAAATGGTGAATTGCCCTCG

NC_045512.2_21mer_win1_27771
27771
27791
3081
AATTAACTGAAGATAAACACG
4063
GCACAAATAGAAGTCAATTAA

NC_045512.2_21mer_win1_27772
27772
27792
3082
ATTAACTGAAGATAAACACGA
4064
AGCACAAATAGAAGTCAATTA

NC_045512.2_21mer_win1_27773
27773
27793
3083
TTAACTGAAGATAAACACGAA
4065
AAGCACAAATAGAAGTCAATT

NC_045512.2_21mer_win1_27774
27774
27794
3084
TAACTGAAGATAAACACGAAA
4066
AAAGCACAAATAGAAGTCAAT

NC_045512.2_21mer_win1_27775
27775
27795
3085
AACTGAAGATAAACACGAAAA
4067
AAAAGCACAAATAGAAGTCAA

NC_045512.2_21mer_win1_27776
27776
27796
3086
ACTGAAGATAAACACGAAAAA
4068
AAAAAGCACAAATAGAAGTCA

NC_045512.2_21mer_win1_27777
27777
27797
3087
CTGAAGATAAACACGAAAAAT
4069
TAAAAAGCACAAATAGAAGTC

NC_045512.2_21mer_win1_27778
27778
27798
3088
TGAAGATAAACACGAAAAATC
4070
CTAAAAAGCACAAATAGAAGT

NC_045512.2_21mer_win1_27779
27779
27799
3089
GAAGATAAACACGAAAAATCG
4071
GCTAAAAAGCACAAATAGAAG

NC_045512.2_21mer_win1_27780
27780
27800
3090
AAGATAAACACGAAAAATCGG
4072
GGCTAAAAAGCACAAATAGAA

NC_045512.2_21mer_win1_27781
27781
27801
3091
AGATAAACACGAAAAATCGGA
4073
AGGCTAAAAAGCACAAATAGA

NC_045512.2_21mer_win1_27782
27782
27802
3092
GATAAACACGAAAAATCGGAA
4074
AAGGCTAAAAAGCACAAATAG

NC_045512.2_21mer_win1_27783
27783
27803
3093
ATAAACACGAAAAATCGGAAA
4075
AAAGGCTAAAAAGCACAAATA

NC_045512.2_21mer_win1_27784
27784
27804
3094
TAAACACGAAAAATCGGAAAG
4076
GAAAGGCTAAAAAGCACAAAT

NC_045512.2_21mer_win1_27785
27785
27805
3095
AAACACGAAAAATCGGAAAGA
4077
AGAAAGGCTAAAAAGCACAAA

NC_045512.2_21mer_win1_27786
27786
27806
3096
AACACGAAAAATCGGAAAGAC
4078
CAGAAAGGCTAAAAAGCACAA

NC_045512.2_21mer_win1_27787
27787
27807
3097
ACACGAAAAATCGGAAAGACG
4079
GCAGAAAGGCTAAAAAGCACA

NC_045512.2_21mer_win1_27788
27788
27808
3098
CACGAAAAATCGGAAAGACGA
4080
AGCAGAAAGGCTAAAAAGCAC

NC_045512.2_21mer_win1_27789
27789
27809
3099
ACGAAAAATCGGAAAGACGAT
4081
TAGCAGAAAGGCTAAAAAGCA

NC_045512.2_21mer_win1_27790
27790
27810
3100
CGAAAAATCGGAAAGACGATA
4082
ATAGCAGAAAGGCTAAAAAGC

NC_045512.2_21mer_win1_27791
27791
27811
3101
GAAAAATCGGAAAGACGATAA
4083
AATAGCAGAAAGGCTAAAAAG

NC_045512.2_21mer_win1_27792
27792
27812
3102
AAAAATCGGAAAGACGATAAG
4084
GAATAGCAGAAAGGCTAAAAA

NC_045512.2_21mer_win1_27793
27793
27813
3103
AAAATCGGAAAGACGATAAGG
4085
GGAATAGCAGAAAGGCTAAAA

NC_045512.2_21mer_win1_27794
27794
27814
3104
AAATCGGAAAGACGATAAGGA
4086
AGGAATAGCAGAAAGGCTAAA

NC_045512.2_21mer_win1_27795
27795
27815
3105
AATCGGAAAGACGATAAGGAA
4087
AAGGAATAGCAGAAAGGCTAA

NC_045512.2_21mer_win1_27796
27796
27816
3106
ATCGGAAAGACGATAAGGAAC
4088
CAAGGAATAGCAGAAAGGCTA

NC_045512.2_21mer_win1_27797
27797
27817
3107
TCGGAAAGACGATAAGGAACA
4089
ACAAGGAATAGCAGAAAGGCT

NC_045512.2_21mer_win1_27798
27798
27818
3108
CGGAAAGACGATAAGGAACAA
4090
AACAAGGAATAGCAGAAAGGC

NC_045512.2_21mer_win1_28270
28270
28290
3109
ATTTTACAGACTATTACCTGG
4091
GGTCCATTATCAGACATTTTA

NC_045512.2_21mer_win1_28271
28271
28291
3110
TTTTACAGACTATTACCTGGG
4092
GGGTCCATTATCAGACATTTT

NC_045512.2_21mer_win1_28272
28272
28292
3111
TTTACAGACTATTACCTGGGG
4093
GGGGTCCATTATCAGACATTT

NC_045512.2_21mer_win1_28273
28273
28293
3112
TTACAGACTATTACCTGGGGT
4094
TGGGGTCCATTATCAGACATT

NC_045512.2_21mer_win1_28274
28274
28294
3113
TACAGACTATTACCTGGGGTT
4095
TTGGGGTCCATTATCAGACAT

NC_045512.2_21mer_win1_28275
28275
28295
3114
ACAGACTATTACCTGGGGTTT
4096
TTTGGGGTCCATTATCAGACA

NC_045512.2_21mer_win1_28276
28276
28296
3115
CAGACTATTACCTGGGGTTTT
4097
TTTTGGGGTCCATTATCAGAC

NC_045512.2_21mer_win1_28397
28397
28417
3116
GGGGTTCCAAATGGGTTATTA
4098
ATTATTGGGTAAACCTTGGGG

NC_045512.2_21mer_win1_28398
28398
28418
3117
GGGTTCCAAATGGGTTATTAT
4099
TATTATTGGGTAAACCTTGGG

NC_045512.2_21mer_win1_28399
28399
28419
3118
GGTTCCAAATGGGTTATTATG
4100
GTATTATTGGGTAAACCTTGG

NC_045512.2_21mer_win1_28400
28400
28420
3119
GTTCCAAATGGGTTATTATGA
4101
AGTATTATTGGGTAAACCTTG

NC_045512.2_21mer_win1_28401
28401
28421
3120
TTCCAAATGGGTTATTATGAC
4102
CAGTATTATTGGGTAAACCTT

NC_045512.2_21mer_win1_28402
28402
28422
3121
TCCAAATGGGTTATTATGACG
4103
GCAGTATTATTGGGTAAACCT

NC_045512.2_21mer_win1_28403
28403
28423
3122
CCAAATGGGTTATTATGACGC
4104
CGCAGTATTATTGGGTAAACC

NC_045512.2_21mer_win1_28404
28404
28424
3123
CAAATGGGTTATTATGACGCA
4105
ACGCAGTATTATTGGGTAAAC

NC_045512.2_21mer_win1_28405
28405
28425
3124
AAATGGGTTATTATGACGCAG
4106
GACGCAGTATTATTGGGTAAA

NC_045512.2_21mer_win1_28406
28406
28426
3125
AATGGGTTATTATGACGCAGA
4107
AGACGCAGTATTATTGGGTAA

NC_045512.2_21mer_win1_28407
28407
28427
3126
ATGGGTTATTATGACGCAGAA
4108
AAGACGCAGTATTATTGGGTA

NC_045512.2_21mer_win1_28408
28408
28428
3127
TGGGTTATTATGACGCAGAAC
4109
CAAGACGCAGTATTATTGGGT

NC_045512.2_21mer_win1_28409
28409
28429
3128
GGGTTATTATGACGCAGAACC
4110
CCAAGACGCAGTATTATTGGG

NC_045512.2_21mer_win1_28410
28410
28430
3129
GGTTATTATGACGCAGAACCA
4111
ACCAAGACGCAGTATTATTGG

NC_045512.2_21mer_win1_28411
28411
28431
3130
GTTATTATGACGCAGAACCAA
4112
AACCAAGACGCAGTATTATTG

NC_045512.2_21mer_win1_28412
28412
28432
3131
TTATTATGACGCAGAACCAAG
4113
GAACCAAGACGCAGTATTATT

NC_045512.2_21mer_win1_28413
28413
28433
3132
TATTATGACGCAGAACCAAGT
4114
TGAACCAAGACGCAGTATTAT

NC_045512.2_21mer_win1_28414
28414
28434
3133
ATTATGACGCAGAACCAAGTG
4115
GTGAACCAAGACGCAGTATTA

NC_045512.2_21mer_win1_28513
28513
28533
3134
TCTACTGGTTTAACCGATGAT
4116
TAGTAGCCAATTTGGTCATCT

NC_045512.2_21mer_win1_28514
28514
28534
3135
CTACTGGTTTAACCGATGATG
4117
GTAGTAGCCAATTTGGTCATC

NC_045512.2_21mer_win1_28515
28515
28535
3136
TACTGGTTTAACCGATGATGG
4118
GGTAGTAGCCAATTTGGTCAT

NC_045512.2_21mer_win1_28516
28516
28536
3137
ACTGGTTTAACCGATGATGGC
4119
CGGTAGTAGCCAATTTGGTCA

NC_045512.2_21mer_win1_28517
28517
28537
3138
CTGGTTTAACCGATGATGGCT
4120
TCGGTAGTAGCCAATTTGGTC

NC_045512.2_21mer_win1_28518
28518
28538
3139
TGGTTTAACCGATGATGGCTT
4121
TTCGGTAGTAGCCAATTTGGT

NC_045512.2_21mer_win1_28519
28519
28539
3140
GGTTTAACCGATGATGGCTTC
4122
CTTCGGTAGTAGCCAATTTGG

NC_045512.2_21mer_win1_28520
28520
28540
3141
GTTTAACCGATGATGGCTTCT
4123
TCTTCGGTAGTAGCCAATTTG

NC_045512.2_21mer_win1_28521
28521
28541
3142
TTTAACCGATGATGGCTTCTC
4124
CTCTTCGGTAGTAGCCAATTT

NC_045512.2_21mer_win1_28522
28522
28542
3143
TTAACCGATGATGGCTTCTCG
4125
GCTCTTCGGTAGTAGCCAATT

NC_045512.2_21mer_win1_28523
28523
28543
3144
TAACCGATGATGGCTTCTCGA
4126
AGCTCTTCGGTAGTAGCCAAT

NC_045512.2_21mer_win1_28524
28524
28544
3145
AACCGATGATGGCTTCTCGAT
4127
TAGCTCTTCGGTAGTAGCCAA

NC_045512.2_21mer_win1_28525
28525
28545
3146
ACCGATGATGGCTTCTCGATG
4128
GTAGCTCTTCGGTAGTAGCCA

NC_045512.2_21mer_win1_28526
28526
28546
3147
CCGATGATGGCTTCTCGATGG
4129
GGTAGCTCTTCGGTAGTAGCC

NC_045512.2_21mer_win1_28706
28706
28726
3148
GTGTAACCGTGGGCGTTAGGA
4130
AGGATTGCGGGTGCCAATGTG

NC_045512.2_21mer_win1_28744
28744
28764
3149
GCACGATGTTGAAGGAGTTCC
4131
CCTTGAGGAAGTTGTAGCACG

NC_045512.2_21mer_win1_28745
28745
28765
3150
CACGATGTTGAAGGAGTTCCT
4132
TCCTTGAGGAAGTTGTAGCAC

NC_045512.2_21mer_win1_28746
28746
28766
3151
ACGATGTTGAAGGAGTTCCTT
4133
TTCCTTGAGGAAGTTGTAGCA

NC_045512.2_21mer_win1_28747
28747
28767
3152
CGATGTTGAAGGAGTTCCTTG
4134
GTTCCTTGAGGAAGTTGTAGC

NC_045512.2_21mer_win1_28748
28748
28768
3153
GATGTTGAAGGAGTTCCTTGT
4135
TGTTCCTTGAGGAAGTTGTAG

NC_045512.2_21mer_win1_28749
28749
28769
3154
ATGTTGAAGGAGTTCCTTGTT
4136
TTGTTCCTTGAGGAAGTTGTA

NC_045512.2_21mer_win1_28750
28750
28770
3155
TGTTGAAGGAGTTCCTTGTTG
4137
GTTGTTCCTTGAGGAAGTTGT

NC_045512.2_21mer_win1_28751
28751
28771
3156
GTTGAAGGAGTTCCTTGTTGT
4138
TGTTGTTCCTTGAGGAAGTTG

NC_045512.2_21mer_win1_28752
28752
28772
3157
TTGAAGGAGTTCCTTGTTGTA
4139
ATGTTGTTCCTTGAGGAAGTT

NC_045512.2_21mer_win1_28753
28753
28773
3158
TGAAGGAGTTCCTTGTTGTAA
4140
AATGTTGTTCCTTGAGGAAGT

NC_045512.2_21mer_win1_28754
28754
28774
3159
GAAGGAGTTCCTTGTTGTAAC
4141
CAATGTTGTTCCTTGAGGAAG

NC_045512.2_21mer_win1_28755
28755
28775
3160
AAGGAGTTCCTTGTTGTAACG
4142
GCAATGTTGTTCCTTGAGGAA

NC_045512.2_21mer_win1_28756
28756
28776
3161
AGGAGTTCCTTGTTGTAACGG
4143
GGCAATGTTGTTCCTTGAGGA

NC_045512.2_21mer_win1_28757
28757
28777
3162
GGAGTTCCTTGTTGTAACGGT
4144
TGGCAATGTTGTTCCTTGAGG

NC_045512.2_21mer_win1_28758
28758
28778
3163
GAGTTCCTTGTTGTAACGGTT
4145
TTGGCAATGTTGTTCCTTGAG

NC_045512.2_21mer_win1_28759
28759
28779
3164
AGTTCCTTGTTGTAACGGTTT
4146
TTTGGCAATGTTGTTCCTTGA

NC_045512.2_21mer_win1_28760
28760
28780
3165
GTTCCTTGTTGTAACGGTTTT
4147
TTTTGGCAATGTTGTTCCTTG

NC_045512.2_21mer_win1_28761
28761
28781
3166
TTCCTTGTTGTAACGGTTTTC
4148
CTTTTGGCAATGTTGTTCCTT

NC_045512.2_21mer_win1_28762
28762
28782
3167
TCCTTGTTGTAACGGTTTTCC
4149
CCTTTTGGCAATGTTGTTCCT

NC_045512.2_21mer_win1_28763
28763
28783
3168
CCTTGTTGTAACGGTTTTCCG
4150
GCCTTTTGGCAATGTTGTTCC

NC_045512.2_21mer_win1_28764
28764
28784
3169
CTTGTTGTAACGGTTTTCCGA
4151
AGCCTTTTGGCAATGTTGTTC

NC_045512.2_21mer_win1_28765
28765
28785
3170
TTGTTGTAACGGTTTTCCGAA
4152
AAGCCTTTTGGCAATGTTGTT

NC_045512.2_21mer_win1_28766
28766
28786
3171
TGTTGTAACGGTTTTCCGAAG
4153
GAAGCCTTTTGGCAATGTTGT

NC_045512.2_21mer_win1_28767
28767
28787
3172
GTTGTAACGGTTTTCCGAAGA
4154
AGAAGCCTTTTGGCAATGTTG

NC_045512.2_21mer_win1_28768
28768
28788
3173
TTGTAACGGTTTTCCGAAGAT
4155
TAGAAGCCTTTTGGCAATGTT

NC_045512.2_21mer_win1_28769
28769
28789
3174
TGTAACGGTTTTCCGAAGATG
4156
GTAGAAGCCTTTTGGCAATGT

NC_045512.2_21mer_win1_28770
28770
28790
3175
GTAACGGTTTTCCGAAGATGC
4157
CGTAGAAGCCTTTTGGCAATG

NC_045512.2_21mer_win1_28771
28771
28791
3176
TAACGGTTTTCCGAAGATGCG
4158
GCGTAGAAGCCTTTTGGCAAT

NC_045512.2_21mer_win1_28772
28772
28792
3177
AACGGTTTTCCGAAGATGCGT
4159
TGCGTAGAAGCCTTTTGGCAA

NC_045512.2_21mer_win1_28773
28773
28793
3178
ACGGTTTTCCGAAGATGCGTC
4160
CTGCGTAGAAGCCTTTTGGCA

NC_045512.2_21mer_win1_28774
28774
28794
3179
CGGTTTTCCGAAGATGCGTCT
4161
TCTGCGTAGAAGCCTTTTGGC

NC_045512.2_21mer_win1_28799
28799
28819
3180
TCGTCTCCGCCGTCAGTTCGG
4162
GGCTTGACTGCCGCCTCTGCT

NC_045512.2_21mer_win1_28800
28800
28820
3181
CGTCTCCGCCGTCAGTTCGGA
4163
AGGCTTGACTGCCGCCTCTGC

NC_045512.2_21mer_win1_28801
28801
28821
3182
GTCTCCGCCGTCAGTTCGGAG
4164
GAGGCTTGACTGCCGCCTCTG

NC_045512.2_21mer_win1_28802
28802
28822
3183
TCTCCGCCGTCAGTTCGGAGA
4165
AGAGGCTTGACTGCCGCCTCT

NC_045512.2_21mer_win1_28803
28803
28823
3184
CTCCGCCGTCAGTTCGGAGAA
4166
AAGAGGCTTGACTGCCGCCTC

NC_045512.2_21mer_win1_28804
28804
28824
3185
TCCGCCGTCAGTTCGGAGAAG
4167
GAAGAGGCTTGACTGCCGCCT

NC_045512.2_21mer_win1_28805
28805
28825
3186
CCGCCGTCAGTTCGGAGAAGA
4168
AGAAGAGGCTTGACTGCCGCC

NC_045512.2_21mer_win1_28806
28806
28826
3187
CGCCGTCAGTTCGGAGAAGAG
4169
GAGAAGAGGCTTGACTGCCGC

NC_045512.2_21mer_win1_28807
28807
28827
3188
GCCGTCAGTTCGGAGAAGAGC
4170
CGAGAAGAGGCTTGACTGCCG

NC_045512.2_21mer_win1_28946
28946
28966
3189
CTGTCTAACTTGGTCGAACTC
4171
CTCAAGCTGGTTCAATCTGTC

NC_045512.2_21mer_win1_28947
28947
28967
3190
TGTCTAACTTGGTCGAACTCT
4172
TCTCAAGCTGGTTCAATCTGT

NC_045512.2_21mer_win1_28948
28948
28968
3191
GTCTAACTTGGTCGAACTCTC
4173
CTCTCAAGCTGGTTCAATCTG

NC_045512.2_21mer_win1_28949
28949
28969
3192
TCTAACTTGGTCGAACTCTCG
4174
GCTCTCAAGCTGGTTCAATCT

NC_045512.2_21mer_win1_28950
28950
28970
3193
CTAACTTGGTCGAACTCTCGT
4175
TGCTCTCAAGCTGGTTCAATC

NC_045512.2_21mer_win1_28951
28951
28971
3194
TAACTTGGTCGAACTCTCGTT
4176
TTGCTCTCAAGCTGGTTCAAT

NC_045512.2_21mer_win1_28952
28952
28972
3195
AACTTGGTCGAACTCTCGTTT
4177
TTTGCTCTCAAGCTGGTTCAA

NC_045512.2_21mer_win1_28976
28976
28996
3196
AGACCATTTCCGGTTGTTGTT
4178
TTGTTGTTGGCCTTTACCAGA

NC_045512.2_21mer_win1_28977
28977
28997
3197
GACCATTTCCGGTTGTTGTTG
4179
GTTGTTGTTGGCCTTTACCAG

NC_045512.2_21mer_win1_28978
28978
28998
3198
ACCATTTCCGGTTGTTGTTGT
4180
TGTTGTTGTTGGCCTTTACCA

NC_045512.2_21mer_win1_28979
28979
28999
3199
CCATTTCCGGTTGTTGTTGTT
4181
TTGTTGTTGTTGGCCTTTACC

NC_045512.2_21mer_win1_28980
28980
29000
3200
CATTTCCGGTTGTTGTTGTTC
4182
CTTGTTGTTGTTGGCCTTTAC

NC_045512.2_21mer_win1_28981
28981
29001
3201
ATTTCCGGTTGTTGTTGTTCC
4183
CCTTGTTGTTGTTGGCCTTTA

NC_045512.2_21mer_win1_28982
28982
29002
3202
TTTCCGGTTGTTGTTGTTCCG
4184
GCCTTGTTGTTGTTGGCCTTT

NC_045512.2_21mer_win1_28983
28983
29003
3203
TTCCGGTTGTTGTTGTTCCGG
4185
GGCCTTGTTGTTGTTGGCCTT

NC_045512.2_21mer_win1_28984
28984
29004
3204
TCCGGTTGTTGTTGTTCCGGT
4186
TGGCCTTGTTGTTGTTGGCCT

NC_045512.2_21mer_win1_28985
28985
29005
3205
CCGGTTGTTGTTGTTCCGGTT
4187
TTGGCCTTGTTGTTGTTGGCC

NC_045512.2_21mer_win1_28986
28986
29006
3206
CGGTTGTTGTTGTTCCGGTTT
4188
TTTGGCCTTGTTGTTGTTGGC

NC_045512.2_21mer_win1_28987
28987
29007
3207
GGTTGTTGTTGTTCCGGTTTG
4189
GTTTGGCCTTGTTGTTGTTGG

NC_045512.2_21mer_win1_28988
28988
29008
3208
GTTGTTGTTGTTCCGGTTTGA
4190
AGTTTGGCCTTGTTGTTGTTG

NC_045512.2_21mer_win1_28989
28989
29009
3209
TTGTTGTTGTTCCGGTTTGAC
4191
CAGTTTGGCCTTGTTGTTGTT

NC_045512.2_21mer_win1_28990
28990
29010
3210
TGTTGTTGTTCCGGTTTGACA
4192
ACAGTTTGGCCTTGTTGTTGT

NC_045512.2_21mer_win1_28991
28991
29011
3211
GTTGTTGTTCCGGTTTGACAG
4193
GACAGTTTGGCCTTGTTGTTG

NC_045512.2_21mer_win1_28992
28992
29012
3212
TTGTTGTTCCGGTTTGACAGT
4194
TGACAGTTTGGCCTTGTTGTT

NC_045512.2_21mer_win1_28993
28993
29013
3213
TGTTGTTCCGGTTTGACAGTG
4195
GTGACAGTTTGGCCTTGTTGT

NC_045512.2_21mer_win1_28994
28994
29014
3214
GTTGTTCCGGTTTGACAGTGA
4196
AGTGACAGTTTGGCCTTGTTG

NC_045512.2_21mer_win1_28995
28995
29015
3215
TTGTTCCGGTTTGACAGTGAT
4197
TAGTGACAGTTTGGCCTTGTT

NC_045512.2_21mer_win1_28996
28996
29016
3216
TGTTCCGGTTTGACAGTGATT
4198
TTAGTGACAGTTTGGCCTTGT

NC_045512.2_21mer_win1_28997
28997
29017
3217
GTTCCGGTTTGACAGTGATTC
4199
CTTAGTGACAGTTTGGCCTTG

NC_045512.2_21mer_win1_28998
28998
29018
3218
TTCCGGTTTGACAGTGATTCT
4200
TCTTAGTGACAGTTTGGCCTT

NC_045512.2_21mer_win1_28999
28999
29019
3219
TCCGGTTTGACAGTGATTCTT
4201
TTCTTAGTGACAGTTTGGCCT

NC_045512.2_21mer_win1_29000
29000
29020
3220
CCGGTTTGACAGTGATTCTTT
4202
TTTCTTAGTGACAGTTTGGCC

NC_045512.2_21mer_win1_29001
29001
29021
3221
CGGTTTGACAGTGATTCTTTA
4203
ATTTCTTAGTGACAGTTTGGC

NC_045512.2_21mer_win1_29002
29002
29022
3222
GGTTTGACAGTGATTCTTTAG
4204
GATTTCTTAGTGACAGTTTGG

NC_045512.2_21mer_win1_29003
29003
29023
3223
GTTTGACAGTGATTCTTTAGA
4205
AGATTTCTTAGTGACAGTTTG

NC_045512.2_21mer_win1_29004
29004
29024
3224
TTTGACAGTGATTCTTTAGAC
4206
CAGATTTCTTAGTGACAGTTT

NC_045512.2_21mer_win1_29005
29005
29025
3225
TTGACAGTGATTCTTTAGACG
4207
GCAGATTTCTTAGTGACAGTT

NC_045512.2_21mer_win1_29006
29006
29026
3226
TGACAGTGATTCTTTAGACGA
4208
AGCAGATTTCTTAGTGACAGT

NC_045512.2_21mer_win1_29007
29007
29027
3227
GACAGTGATTCTTTAGACGAC
4209
CAGCAGATTTCTTAGTGACAG

NC_045512.2_21mer_win1_29008
29008
29028
3228
ACAGTGATTCTTTAGACGACG
4210
GCAGCAGATTTCTTAGTGACA

NC_045512.2_21mer_win1_29009
29009
29029
3229
CAGTGATTCTTTAGACGACGA
4211
AGCAGCAGATTTCTTAGTGAC

NC_045512.2_21mer_win1_29010
29010
29030
3230
AGTGATTCTTTAGACGACGAC
4212
CAGCAGCAGATTTCTTAGTGA

NC_045512.2_21mer_win1_29011
29011
29031
3231
GTGATTCTTTAGACGACGACT
4213
TCAGCAGCAGATTTCTTAGTG

NC_045512.2_21mer_win1_29012
29012
29032
3232
TGATTCTTTAGACGACGACTC
4214
CTCAGCAGCAGATTTCTTAGT

NC_045512.2_21mer_win1_29013
29013
29033
3233
GATTCTTTAGACGACGACTCC
4215
CCTCAGCAGCAGATTTCTTAG

NC_045512.2_21mer_win1_29014
29014
29034
3234
ATTCTTTAGACGACGACTCCG
4216
GCCTCAGCAGCAGATTTCTTA

NC_045512.2_21mer_win1_29144
29144
29164
3235
GATTAGTCTGTTCCTTGACTA
4217
ATCAGTTCCTTGTCTGATTAG

NC_045512.2_21mer_win1_29145
29145
29165
3236
ATTAGTCTGTTCCTTGACTAA
4218
AATCAGTTCCTTGTCTGATTA

NC_045512.2_21mer_win1_29146
29146
29166
3237
TTAGTCTGTTCCTTGACTAAT
4219
TAATCAGTTCCTTGTCTGATT

NC_045512.2_21mer_win1_29147
29147
29167
3238
TAGTCTGTTCCTTGACTAATG
4220
GTAATCAGTTCCTTGTCTGAT

NC_045512.2_21mer_win1_29148
29148
29168
3239
AGTCTGTTCCTTGACTAATGT
4221
TGTAATCAGTTCCTTGTCTGA

NC_045512.2_21mer_win1_29149
29149
29169
3240
GTCTGTTCCTTGACTAATGTT
4222
TTGTAATCAGTTCCTTGTCTG

NC_045512.2_21mer_win1_29150
29150
29170
3241
TCTGTTCCTTGACTAATGTTT
4223
TTTGTAATCAGTTCCTTGTCT

NC_045512.2_21mer_win1_29151
29151
29171
3242
CTGTTCCTTGACTAATGTTTG
4224
GTTTGTAATCAGTTCCTTGTC

NC_045512.2_21mer_win1_29152
29152
29172
3243
TGTTCCTTGACTAATGTTTGT
4225
TGTTTGTAATCAGTTCCTTGT

NC_045512.2_21mer_win1_29174
29174
29194
3244
ACCGGCGTTTAACGTGTTAAA
4226
AAATTGTGCAATTTGCGGCCA

NC_045512.2_21mer_win1_29175
29175
29195
3245
CCGGCGTTTAACGTGTTAAAC
4227
CAAATTGTGCAATTTGCGGCC

NC_045512.2_21mer_win1_29176
29176
29196
3246
CGGCGTTTAACGTGTTAAACG
4228
GCAAATTGTGCAATTTGCGGC

NC_045512.2_21mer_win1_29228
29228
29248
3247
GCGTAACCGTACCTTCAGTGT
4229
TGTGACTTCCATGCCAATGCG

NC_045512.2_21mer_win1_29229
29229
29249
3248
CGTAACCGTACCTTCAGTGTG
4230
GTGTGACTTCCATGCCAATGC

NC_045512.2_21mer_win1_29230
29230
29250
3249
GTAACCGTACCTTCAGTGTGG
4231
GGTGTGACTTCCATGCCAATG

NC_045512.2_21mer_win1_29231
29231
29251
3250
TAACCGTACCTTCAGTGTGGA
4232
AGGTGTGACTTCCATGCCAAT

NC_045512.2_21mer_win1_29232
29232
29252
3251
AACCGTACCTTCAGTGTGGAA
4233
AAGGTGTGACTTCCATGCCAA

NC_045512.2_21mer_win1_29233
29233
29253
3252
ACCGTACCTTCAGTGTGGAAG
4234
GAAGGTGTGACTTCCATGCCA

NC_045512.2_21mer_win1_29234
29234
29254
3253
CCGTACCTTCAGTGTGGAAGC
4235
CGAAGGTGTGACTTCCATGCC

NC_045512.2_21mer_win1_29235
29235
29255
3254
CGTACCTTCAGTGTGGAAGCC
4236
CCGAAGGTGTGACTTCCATGC

NC_045512.2_21mer_win1_29236
29236
29256
3255
GTACCTTCAGTGTGGAAGCCC
4237
CCCGAAGGTGTGACTTCCATG

NC_045512.2_21mer_win1_29237
29237
29257
3256
TACCTTCAGTGTGGAAGCCCT
4238
TCCCGAAGGTGTGACTTCCAT

NC_045512.2_21mer_win1_29238
29238
29258
3257
ACCTTCAGTGTGGAAGCCCTT
4239
TTCCCGAAGGTGTGACTTCCA

NC_045512.2_21mer_win1_29239
29239
29259
3258
CCTTCAGTGTGGAAGCCCTTG
4240
GTTCCCGAAGGTGTGACTTCC

NC_045512.2_21mer_win1_29285
29285
29305
3259
TTTAACCTACTGTTTCTAGGT
4241
TGGATCTTTGTCATCCAATTT

NC_045512.2_21mer_win1_29342
29342
29362
3260
TAACTGCGTATGTTTTGTAAG
4242
GAATGTTTTGTATGCGTCAAT

NC_045512.2_21mer_win1_29343
29343
29363
3261
AACTGCGTATGTTTTGTAAGG
4243
GGAATGTTTTGTATGCGTCAA

NC_045512.2_21mer_win1_29344
29344
29364
3262
ACTGCGTATGTTTTGTAAGGG
4244
GGGAATGTTTTGTATGCGTCA

NC_045512.2_21mer_win1_29345
29345
29365
3263
CTGCGTATGTTTTGTAAGGGT
4245
TGGGAATGTTTTGTATGCGTC

NC_045512.2_21mer_win1_29346
29346
29366
3264
TGCGTATGTTTTGTAAGGGTG
4246
GTGGGAATGTTTTGTATGCGT

NC_045512.2_21mer_win1_29347
29347
29367
3265
GCGTATGTTTTGTAAGGGTGG
4247
GGTGGGAATGTTTTGTATGCG

NC_045512.2_21mer_win1_29348
29348
29368
3266
CGTATGTTTTGTAAGGGTGGT
4248
TGGTGGGAATGTTTTGTATGC

NC_045512.2_21mer_win1_29349
29349
29369
3267
GTATGTTTTGTAAGGGTGGTT
4249
TTGGTGGGAATGTTTTGTATG

NC_045512.2_21mer_win1_29350
29350
29370
3268
TATGTTTTGTAAGGGTGGTTG
4250
GTTGGTGGGAATGTTTTGTAT

NC_045512.2_21mer_win1_29351
29351
29371
3269
ATGTTTTGTAAGGGTGGTTGT
4251
TGTTGGTGGGAATGTTTTGTA

NC_045512.2_21mer_win1_29352
29352
29372
3270
TGTTTTGTAAGGGTGGTTGTC
4252
CTGTTGGTGGGAATGTTTTGT

NC_045512.2_21mer_win1_29353
29353
29373
3271
GTTTTGTAAGGGTGGTTGTCT
4253
TCTGTTGGTGGGAATGTTTTG

NC_045512.2_21mer_win1_29354
29354
29374
3272
TTTTGTAAGGGTGGTTGTCTC
4254
CTCTGTTGGTGGGAATGTTTT

NC_045512.2_21mer_win1_29355
29355
29375
3273
TTTGTAAGGGTGGTTGTCTCG
4255
GCTCTGTTGGTGGGAATGTTT

NC_045512.2_21mer_win1_29356
29356
29376
3274
TTGTAAGGGTGGTTGTCTCGG
4256
GGCTCTGTTGGTGGGAATGTT

NC_045512.2_21mer_win1_29357
29357
29377
3275
TGTAAGGGTGGTTGTCTCGGA
4257
AGGCTCTGTTGGTGGGAATGT

NC_045512.2_21mer_win1_29358
29358
29378
3276
GTAAGGGTGGTTGTCTCGGAT
4258
TAGGCTCTGTTGGTGGGAATG

NC_045512.2_21mer_win1_29359
29359
29379
3277
TAAGGGTGGTTGTCTCGGATT
4259
TTAGGCTCTGTTGGTGGGAAT

NC_045512.2_21mer_win1_29360
29360
29380
3278
AAGGGTGGTTGTCTCGGATTT
4260
TTTAGGCTCTGTTGGTGGGAA

NC_045512.2_2lmer_win1_29361
29361
29381
3279
AGGGTGGTTGTCTCGGATTTT
4261
TTTTAGGCTCTGTTGGTGGGA

NC_045512.2_21mer_win1_29362
29362
29382
3280
GGGTGGTTGTCTCGGATTTTT
4262
TTTTTAGGCTCTGTTGGTGGG

NC_045512.2_21mer_win1_29363
29363
29383
3281
GGTGGTTGTCTCGGATTTTTC
4263
CTTTTTAGGCTCTGTTGGTGG

NC_045512.2_21mer_win1_29364
29364
29384
3282
GTGGTTGTCTCGGATTTTTCC
4264
CCTTTTTAGGCTCTGTTGGTG

NC_045512.2_21mer_win1_29365
29365
29385
3283
TGGTTGTCTCGGATTTTTCCT
4265
TCCTTTTTAGGCTCTGTTGGT

NC_045512.2_21mer_win1_29366
29366
29386
3284
GGTTGTCTCGGATTTTTCCTG
4266
GTCCTTTTTAGGCTCTGTTGG

NC_045512.2_21mer_win1_29367
29367
29387
3285
GTTGTCTCGGATTTTTCCTGT
4267
TGTCCTTTTTAGGCTCTGTTG

NC_045512.2_21mer_win1_29368
29368
29388
3286
TTGTCTCGGATTTTTCCTGTT
4268
TTGTCCTTTTTAGGCTCTGTT

NC_045512.2_21mer_win1_29369
29369
29389
3287
TGTCTCGGATTTTTCCTGTTT
4269
TTTGTCCTTTTTAGGCTCTGT

NC_045512.2_21mer_win1_29370
29370
29390
3288
GTCTCGGATTTTTCCTGTTTT
4270
TTTTGTCCTTTTTAGGCTCTG

NC_045512.2_2lmer_win1_29371
29371
29391
3289
TCTCGGATTTTTCCTGTTTTT
4271
TTTTTGTCCTTTTTAGGCTCT

NC_045512.2_21mer_win1_29372
29372
29392
3290
CTCGGATTTTTCCTGTTTTTC
4272
CTTTTTGTCCTTTTTAGGCTC

NC_045512.2_21mer_win1_29373
29373
29393
3291
TCGGATTTTTCCTGTTTTTCT
4273
TCTTTTTGTCCTTTTTAGGCT

NC_045512.2_21mer_win1_29374
29374
29394
3292
CGGATTTTTCCTGTTTTTCTT
4274
TTCTTTTTGTCCTTTTTAGGC

NC_045512.2_21mer_win1_29543
29543
29563
3293
CTGGTGTGTTCCGTCTACCCG
4275
GCCCATCTGCCTTGTGTGGTC

NC_045512.2_21mer_win1_29544
29544
29564
3294
TGGTGTGTTCCGTCTACCCGA
4276
AGCCCATCTGCCTTGTGTGGT

NC_045512.2_21mer_win1_29545
29545
29565
3295
GGTGTGTTCCGTCTACCCGAT
4277
TAGCCCATCTGCCTTGTGTGG

NC_045512.2_21mer_win1_29546
29546
29566
3296
GTGTGTTCCGTCTACCCGATA
4278
ATAGCCCATCTGCCTTGTGTG

NC_045512.2_21mer_win1_29598
29598
29618
3297
TATCAGATGAGAACACGTCTT
4279
TTCTGCACAAGAGTAGACTAT

NC_045512.2_21mer_win1_29599
29599
29619
3298
ATCAGATGAGAACACGTCTTA
4280
ATTCTGCACAAGAGTAGACTA

NC_045512.2_21mer_win1_29600
29600
29620
3299
TCAGATGAGAACACGTCTTAC
4281
CATTCTGCACAAGAGTAGACT

NC_045512.2_21mer_win1_29601
29601
29621
3300
CAGATGAGAACACGTCTTACT
4282
TCATTCTGCACAAGAGTAGAC

NC_045512.2_21mer_win1_29602
29602
29622
3301
AGATGAGAACACGTCTTACTT
4283
TTCATTCTGCACAAGAGTAGA

NC_045512.2_21mer_win1_29603
29603
29623
3302
GATGAGAACACGTCTTACTTA
4284
ATTCATTCTGCACAAGAGTAG

NC_045512.2_21mer_win1_29604
29604
29624
3303
ATGAGAACACGTCTTACTTAA
4285
AATTCATTCTGCACAAGAGTA

NC_045512.2_21mer_win1_29605
29605
29625
3304
TGAGAACACGTCTTACTTAAG
4286
GAATTCATTCTGCACAAGAGT

NC_045512.2_21mer_win1_29606
29606
29626
3305
GAGAACACGTCTTACTTAAGA
4287
AGAATTCATTCTGCACAAGAG

NC_045512.2_21mer_win1_29607
29607
29627
3306
AGAACACGTCTTACTTAAGAG
4288
GAGAATTCATTCTGCACAAGA

NC_045512.2_21mer_win1_29608
29608
29628
3307
GAACACGTCTTACTTAAGAGC
4289
CGAGAATTCATTCTGCACAAG

NC_045512.2_21mer_win1_29609
29609
29629
3308
AACACGTCTTACTTAAGAGCA
4290
ACGAGAATTCATTCTGCACAA

NC_045512.2_21mer_win1_29610
29610
29630
3309
ACACGTCTTACTTAAGAGCAT
4291
TACGAGAATTCATTCTGCACA

NC_045512.2_21mer_win1_29652
29652
29672
3310
ATCAATTGAAATTAGAGTGTA
4292
ATGTGAGATTAAAGTTAACTA

NC_045512.2_21mer_win1_29653
29653
29673
3311
TCAATTGAAATTAGAGTGTAT
4293
TATGTGAGATTAAAGTTAACT

NC_045512.2_21mer_win1_29654
29654
29674
3312
CAATTGAAATTAGAGTGTATC
4294
CTATGTGAGATTAAAGTTAAC

NC_045512.2_21mer_win1_29655
29655
29675
3313
AATTGAAATTAGAGTGTATCG
4295
GCTATGTGAGATTAAAGTTAA

NC_045512.2_21mer_win1_29656
29656
29676
3314
ATTGAAATTAGAGTGTATCGT
4296
TGCTATGTGAGATTAAAGTTA

NC_045512.2_21mer_win1_29657
29657
29677
3315
TTGAAATTAGAGTGTATCGTT
4297
TTGCTATGTGAGATTAAAGTT

NC_045512.2_21mer_win1_29658
29658
29678
3316
TGAAATTAGAGTGTATCGTTA
4298
ATTGCTATGTGAGATTAAAGT

NC_045512.2_21mer_win1_29659
29659
29679
3317
GAAATTAGAGTGTATCGTTAG
4299
GATTGCTATGTGAGATTAAAG

NC_045512.2_21mer_win1_29660
29660
29680
3318
AAATTAGAGTGTATCGTTAGA
4300
AGATTGCTATGTGAGATTAAA

NC_045512.2_21mer_win1_29661
29661
29681
3319
AATTAGAGTGTATCGTTAGAA
4301
AAGATTGCTATGTGAGATTAA

NC_045512.2_21mer_win1_29662
29662
29682
3320
ATTAGAGTGTATCGTTAGAAA
4302
AAAGATTGCTATGTGAGATTA

NC_045512.2_21mer_win1_29663
29663
29683
3321
TTAGAGTGTATCGTTAGAAAT
4303
TAAAGATTGCTATGTGAGATT

NC_045512.2_21mer_win1_29664
29664
29684
3322
TAGAGTGTATCGTTAGAAATT
4304
TTAAAGATTGCTATGTGAGAT

NC_045512.2_21mer_win1_29665
29665
29685
3323
AGAGTGTATCGTTAGAAATTA
4305
ATTAAAGATTGCTATGTGAGA

NC_045512.2_21mer_win1_29666
29666
29686
3324
GAGTGTATCGTTAGAAATTAG
4306
GATTAAAGATTGCTATGTGAG

NC_045512.2_21mer_win1_29667
29667
29687
3325
AGTGTATCGTTAGAAATTAGT
4307
TGATTAAAGATTGCTATGTGA

NC_045512.2_21mer_win1_29689
29689
29709
3326
ACACATTGTAATCCCTCCTGA
4308
AGTCCTCCCTAATGTTACACA

NC_045512.2_21mer_win1_29690
29690
29710
3327
CACATTGTAATCCCTCCTGAA
4309
AAGTCCTCCCTAATGTTACAC

NC_045512.2_21mer_win1_29691
29691
29711
3328
ACATTGTAATCCCTCCTGAAC
4310
CAAGTCCTCCCTAATGTTACA

NC_045512.2_21mer_win1_29692
29692
29712
3329
CATTGTAATCCCTCCTGAACT
4311
TCAAGTCCTCCCTAATGTTAC

NC_045512.2_21mer_win1_29693
29693
29713
3330
ATTGTAATCCCTCCTGAACTT
4312
TTCAAGTCCTCCCTAATGTTA

NC_045512.2_21mer_win1_29694
29694
29714
3331
TTGTAATCCCTCCTGAACTTT
4313
TTTCAAGTCCTCCCTAATGTT

NC_045512.2_21mer_win1_29695
29695
29715
3332
TGTAATCCCTCCTGAACTTTC
4314
CTTTCAAGTCCTCCCTAATGT

NC_045512.2_21mer_win1_29696
29696
29716
3333
GTAATCCCTCCTGAACTTTCT
4315
TCTTTCAAGTCCTCCCTAATG

NC_045512.2_21mer_win1_29697
29697
29717
3334
TAATCCCTCCTGAACTTTCTC
4316
CTCTTTCAAGTCCTCCCTAAT

NC_045512.2_21mer_win1_29698
29698
29718
3335
AATCCCTCCTGAACTTTCTCG
4317
GCTCTTTCAAGTCCTCCCTAA

NC_045512.2_21mer_win1_29699
29699
29719
3336
ATCCCTCCTGAACTTTCTCGG
4318
GGCTCTTTCAAGTCCTCCCTA

NC_045512.2_21mer_win1_29700
29700
29720
3337
TCCCTCCTGAACTTTCTCGGT
4319
TGGCTCTTTCAAGTCCTCCCT

NC_045512.2_21mer_win1_29701
29701
29721
3338
CCCTCCTGAACTTTCTCGGTG
4320
GTGGCTCTTTCAAGTCCTCCC

NC_045512.2_21mer_win1_29702
29702
29722
3339
CCTCCTGAACTTTCTCGGTGG
4321
GGTGGCTCTTTCAAGTCCTCC

NC_045512.2_21mer_win1_29703
29703
29723
3340
CTCCTGAACTTTCTCGGTGGT
4322
TGGTGGCTCTTTCAAGTCCTC

NC_045512.2_21mer_win1_29704
29704
29724
3341
TCCTGAACTTTCTCGGTGGTG
4323
GTGGTGGCTCTTTCAAGTCCT

NC_045512.2_21mer_win1_29705
29705
29725
3342
CCTGAACTTTCTCGGTGGTGT
4324
TGTGGTGGCTCTTTCAAGTCC

NC_045512.2_21mer_win1_29706
29706
29726
3343
CTGAACTTTCTCGGTGGTGTA
4325
ATGTGGTGGCTCTTTCAAGTC

NC_045512.2_21mer_win1_29707
29707
29727
3344
TGAACTTTCTCGGTGGTGTAA
4326
AATGTGGTGGCTCTTTCAAGT

NC_045512.2_21mer_win1_29708
29708
29728
3345
GAACTTTCTCGGTGGTGTAAA
4327
AAATGTGGTGGCTCTTTCAAG

NC_045512.2_21mer_win1_29709
29709
29729
3346
AACTTTCTCGGTGGTGTAAAA
4328
AAAATGTGGTGGCTCTTTCAA

NC_045512.2_21mer_win1_29710
29710
29730
3347
ACTTTCTCGGTGGTGTAAAAG
4329
GAAAATGTGGTGGCTCTTTCA

NC_045512.2_21mer_win1_29711
29711
29731
3348
CTTTCTCGGTGGTGTAAAAGT
4330
TGAAAATGTGGTGGCTCTTTC

NC_045512.2_21mer_win1_29733
29733
29753
3349
GCTCCGGTGCGCCTCATGCTA
4331
ATCGTACTCCGCGTGGCCTCG

NC_045512.2_21mer_win1_29734
29734
29754
3350
CTCCGGTGCGCCTCATGCTAG
4332
GATCGTACTCCGCGTGGCCTC

NC_045512.2_21mer_win1_29735
29735
29755
3351
TCCGGTGCGCCTCATGCTAGC
4333
CGATCGTACTCCGCGTGGCCT

NC_045512.2_21mer_win1_29736
29736
29756
3352
CCGGTGCGCCTCATGCTAGCT
4334
TCGATCGTACTCCGCGTGGCC

NC_045512.2_21mer_win1_29737
29737
29757
3353
CGGTGCGCCTCATGCTAGCTC
4335
CTCGATCGTACTCCGCGTGGC

NC_045512.2_21mer_win1_29770
29770
29790
3354
TTACGATCCCTCTCGACGGAT
4336
TAGGCAGCTCTCCCTAGCATT

NC_045512.2_21mer_win1_29771
29771
29791
3355
TACGATCCCTCTCGACGGATA
4337
ATAGGCAGCTCTCCCTAGCAT

NC_045512.2_21mer_win1_29772
29772
29792
3356
ACGATCCCTCTCGACGGATAT
4338
TATAGGCAGCTCTCCCTAGCA

NC_045512.2_21mer_win1_29773
29773
29793
3357
CGATCCCTCTCGACGGATATA
4339
ATATAGGCAGCTCTCCCTAGC

NC_045512.2_21mer_win1_29774
29774
29794
3358
GATCCCTCTCGACGGATATAC
4340
CATATAGGCAGCTCTCCCTAG

NC_045512.2_21mer_win1_29775
29775
29795
3359
ATCCCTCTCGACGGATATACC
4341
CCATATAGGCAGCTCTCCCTA

NC_045512.2_21mer_win1_29776
29776
29796
3360
TCCCTCTCGACGGATATACCT
4342
TCCATATAGGCAGCTCTCCCT

NC_045512.2_21mer_win1_29777
29777
29797
3361
CCCTCTCGACGGATATACCTT
4343
TTCCATATAGGCAGCTCTCCC

NC_045512.2_21mer_win1_29778
29778
29798
3362
CCTCTCGACGGATATACCTTC
4344
CTTCCATATAGGCAGCTCTCC

NC_045512.2_21mer_win1_29779
29779
29799
3363
CTCTCGACGGATATACCTTCT
4345
TCTTCCATATAGGCAGCTCTC

NC_045512.2_21mer_win1_29780
29780
29800
3364
TCTCGACGGATATACCTTCTC
4346
CTCTTCCATATAGGCAGCTCT

NC_045512.2_2lmer_win1_29781
29781
29801
3365
CTCGACGGATATACCTTCTCG
4347
GCTCTTCCATATAGGCAGCTC

NC_045512.2_21mer_win1_29782
29782
29802
3366
TCGACGGATATACCTTCTCGG
4348
GGCTCTTCCATATAGGCAGCT

NC_045512.2_21mer_win1_29783
29783
29803
3367
CGACGGATATACCTTCTCGGG
4349
GGGCTCTTCCATATAGGCAGC

NC_045512.2_21mer_win1_29784
29784
29804
3368
GACGGATATACCTTCTCGGGA
4350
AGGGCTCTTCCATATAGGCAG

NC_045512.2_21mer_win1_29785
29785
29805
3369
ACGGATATACCTTCTCGGGAT
4351
TAGGGCTCTTCCATATAGGCA

NC_045512.2_21mer_win1_29786
29786
29806
3370
CGGATATACCTTCTCGGGATT
4352
TTAGGGCTCTTCCATATAGGC

NC_045512.2_21mer_win1_29787
29787
29807
3371
GGATATACCTTCTCGGGATTA
4353
ATTAGGGCTCTTCCATATAGG

NC_045512.2_21mer_win1_29788
29788
29808
3372
GATATACCTTCTCGGGATTAC
4354
CATTAGGGCTCTTCCATATAG

NC_045512.2_21mer_win1_29789
29789
29809
3373
ATATACCTTCTCGGGATTACA
4355
ACATTAGGGCTCTTCCATATA

NC_045512.2_21mer_win1_29790
29790
29810
3374
TATACCTTCTCGGGATTACAC
4356
CACATTAGGGCTCTTCCATAT

NC_045512.2_2lmer_win1_29791
29791
29811
3375
ATACCTTCTCGGGATTACACA
4357
ACACATTAGGGCTCTTCCATA

NC_045512.2_21mer_win1_29792
29792
29812
3376
TACCTTCTCGGGATTACACAT
4358
TACACATTAGGGCTCTTCCAT

NC_045512.2_21mer_win1_29793
29793
29813
3377
ACCTTCTCGGGATTACACATT
4359
TTACACATTAGGGCTCTTCCA

NC_045512.2_21mer_win1_29794
29794
29814
3378
CCTTCTCGGGATTACACATTT
4360
TTTACACATTAGGGCTCTTCC

NC_045512.2_21mer_win1_29795
29795
29815
3379
CTTCTCGGGATTACACATTTT
4361
TTTTACACATTAGGGCTCTTC

NC_045512.2_21mer_win1_29796
29796
29816
3380
TTCTCGGGATTACACATTTTA
4362
ATTTTACACATTAGGGCTCTT

NC_045512.2_21mer_win1_29797
29797
29817
3381
TCTCGGGATTACACATTTTAA
4363
AATTTTACACATTAGGGCTCT

NC_045512.2_21mer_win1_29798
29798
29818
3382
CTCGGGATTACACATTTTAAT
4364
TAATTTTACACATTAGGGCTC

NC_045512.2_21mer_win1_29799
29799
29819
3383
TCGGGATTACACATTTTAATT
4365
TTAATTTTACACATTAGGGCT

NC_045512.2_21mer_win1_29800
29800
29820
3384
CGGGATTACACATTTTAATTA
4366
ATTAATTTTACACATTAGGGC

NC_045512.2_21mer_win1_29801
29801
29821
3385
GGGATTACACATTTTAATTAA
4367
AATTAATTTTACACATTAGGG

NC_045512.2_21mer_win1_29802
29802
29822
3386
GGATTACACATTTTAATTAAA
4368
AAATTAATTTTACACATTAGG

NC_045512.2_21mer_win1_29803
29803
29823
3387
GATTACACATTTTAATTAAAA
4369
AAAATTAATTTTACACATTAG

NC_045512.2_21mer_win1_29804
29804
29824
3388
ATTACACATTTTAATTAAAAT
4370
TAAAATTAATTTTACACATTA

NC_045512.2_21mer_win1_29805
29805
29825
3389
TTACACATTTTAATTAAAATC
4371
CTAAAATTAATTTTACACATT

NC_045512.2_21mer_win1_29806
29806
29826
3390
TACACATTTTAATTAAAATCA
4372
ACTAAAATTAATTTTACACAT

NC_045512.2_21mer_win1_29807
29807
29827
3391
ACACATTTTAATTAAAATCAT
4373
TACTAAAATTAATTTTACACA

NC_045512.2_21mer_win1_29808
29808
29828
3392
CACATTTTAATTAAAATCATC
4374
CTACTAAAATTAATTTTACAC

TABLE 2

Genome Sequences for Coronaviruses

SEQ

ID
Des-

NO
cription
Sequence

2407
SARS-CoV-
attaaaggtttataccttcccaggtaacaaaccaaccaactttcgatctcttgtagatctgttctctaaacgaactttaaaatctgtgtggctgtcactcggctgcatgcttagtgc

2 genome
actcacgcagtataattaataactaattactgtcgttgacaggacacgagtaactcgtctatcttctgcaggctgcttacggtttcgtccgtgttgcagccgatcatcagcacat

(Genbank
ctaggtttcgtccgggtgtgaccgaaaggtaagatggagagccttgtccctggtttcaacgagaaaacacacgtccaactcagtttgcctgttttacaggttcgcgacgtgct

Accession
cgtacgtggctttggagactccgtggaggaggtatatcagaggcacgtcaacatcttaaagatggcacttgtggcttagtagaagttgaaaaaggcgttttgcctcaacttg

No.
aacagccctatgtgttcatcaaacgttcggatgctcgaactgcacctcatggtcatgttatggttgagctggtagcagaactcgaaggcattcagtacggtcgtagtggtgag

NC_
acacttggtgtccttgtccctcatgtgggcgaaataccagtggcttaccgcaaggttcttcttcgtaagaacggtaataaaggagctggtggccatagttacggcgccgatct

045512.2)
aaagtcatttgacttaggcgacgagcttggcactgatccttatgaagattttcaagaaaactggaacactaaacatagcagtggtgttacccgtgaactcatgcgtgagctta

acggaggggcatacactcgctatgtcgataacaacttctgtggccctgatggctaccctcttgagtgcattaaagaccttctagcacgtgctggtaaagcttcatgcactttgt

ccgaacaactggactttattgacactaagaggggtgtatactgctgccgtgaacatgagcatgaaattgcttggtacacggaacgttctgaaaagagctatgaattgcagac

acatttgaaattaaattggcaaagaaatttgacaccttcaatggggaatgtccaaattttgtatttcccttaaattccataatcaagactattcaaccaagggttgaaaagaaaa

agcttgatggctttatgggtagaattcgatctgtctatccagttgcgtcaccaaatgaatgcaaccaaatgtgcctttcaactctcatgaagtgtgatcattgtggtgaaacttca

tggcagacgggcgattttgttaaagccacttgcgaattttgtggcactgagaatttgactaaagaaggtgccactacttgtggttacttaccccaaaatgctgttgttaaaattta

ttgtccagcatgtcacaattcagaagtaggacctgagcatagtcttgccgaataccataatgaatctggcttgaaaaccattcttcgtaagggtggtcgcactattgcctttgga

ggctgtgtgttctcttatgttggttgccataacaagtgtgcctattgggttccacgtgctagcgctaacataggttgtaaccatacaggtgttgttggagaaggttccgaaggtc

ttaatgacaaccttcttgaaatactccaaaaagagaaagtcaacatcaatattgttggtgactttaaacttaatgaagagatcgccattattttggcatctttttctgcttccacaag

tgatttgtggaaactgtgaaaggtttggattataaagcattcaaacaaattgttgaatcctgtggtaattttaaagttacaaaaggaaaagctaaaaaaggtgcctggaatattg

gtgaacagaaatcaatactgagtcctattatgcatttgcatcagaggctgctcgtgttgtacgatcaattttctcccgcactcttgaaactgctcaaaattctgtgcgtgttttaca

gaaggccgctataacaatactagatggaatttcacagtattcactgagactcattgatgctatgatgttcacatctgatttggctactaacaatctagttgtaatggcctacattac

aggtggtgttgttcagttgacttcgcagtggctaactaacatattggcactgtttatgaaaaactcaaacccgtccttgattggcttgaagagaagtttaaggaaggtgtagag

tttcttagagacggttgggaaattgttaaatttatctcaacctgtgcttgtgaaattgtcggtggacaaattgtcacctgtgcaaaggaaattaaggagagtgttcagacattcttt

aagcttgtaaataaatttttggctttgtgtgctgactctatcattattggtggagctaaacttaaagccttgaatttaggtgaaacatttgtcacgcactcaaagggattgtacaga

aagtgtgttaaatccagagaagaaactggcctactcatgcctctaaaagccccaaaagaaattatcttcttagagggagaaacacttcccacagaagtgttaacagaggaa

gttgtcttgaaaactggtgatttacaaccattagaacaacctactagtgaagctgttgaagctccattggttggtacaccagtttgtattaacgggcttatgttgctcgaaatcaa

agacacagaaaagtactgtgccatgcacctaatatgatggtaacaaacaataccttcacactcaaaggcggtgcaccaacaaaggttacttttggtgatgacactgtgata

gaagtgcaaggttacaagagtgtgaatatcacttttgaacttgatgaaaggattgataaagtacttaatgagaagtgctctgcctatacagttgaactcggtacagaagtaaat

gagttcgcctgtgttgtggcagatgctgtcataaaaactttgcaaccagtatctgaattacttacaccactgggcattgatttagatgagtggagtatggctacatactacttattt

gatgagtaggtgagtttaaattggcttcacatatgtattgttattctaccctccagatgaggatgaagaagaaggtgattgtgaagaagaagagtttgagccatcaactcaat

atgagtatggtactgaagatgattaccaaggtaaacctttggaatttggtgccacttctgctgacttcaacctgaagaagagcaagaagaagattggttagatgatgatagtc

aacaaactgttggtcaacaagacggcagtgaggacaatcagacaactactattcaaacaattgttgaggttcaacctcaattagagatggaacttacaccagttgttcagact

attgaagtgaatagttttagtggttatttaaaacttactgacaatgtatacattaaaaatgcagacattgtggaagaagctaaaaaggtaaaaccaacagtggttgttaatgcag

ccaatgtttaccttaaacatggaggaggtgttgcaggagccttaaataaggctactaacaatgccatgcaagttgaatctgatgattacatagctactaatggaccacttaaag

tgggtggtagttgtgttttaagcggacacaatcttgctaaacactgtcttcatgttgtcggcccaaatgttaacaaaggtgaagacattcaacttcttaagagtgcttatgaaaat

tttaatcagcacgaagttctacttgcaccattattatcagaggtatttttggtgctgaccctatacattattaagagtttgtgtagatactgttcgcacaaatgtctacttagctgtc

tttgataaaaatctctatgacaaacttgtttcaagattttggaaatgaagagtgaaaagcaagttgaacaaaagatcgctgagattcctaaagaggaagttaagccatttataa

ctgaaagtaaaccttcagttgaacagagaaaacaagatgataagaaaatcaaagcttgtgttgaagaagttacaacaactctggaagaaactaagttcctcacagaaaactt

gttactttatattgacattaatggcaatcttcatccagattctgccactcttgttagtgacattgacatcactttcttaaagaaagatgctccatatatagtgggtgatgttgttcaag

agggtgttttaactgctgtggttatacctactaaaaaggctggtggcactactgaaatgctagcgaaagctttgagaaaagtgccaacagacaattatataaccacttacccg

ggtcagggtttaaatggttacactgtagaggaggcaaagacagtgcttaaaaagtgtaaaagtgccttttacattctaccatctattatctctaatgagaagcaagaaattcttg

gaactgtttcttggaatttgcgagaaatgcttgcacatgcagaagaaacacgcaaattaatgcctgtagtgtggaaactaaagccatagtttcaactatacagcgtaaatata

agggtattaaaatacaagagggtgtggttgattatggtgctagattttacttttacaccagtaaaacaactgtagcgtcacttatcaacacacttaacgatctaaatgaaactctt

gttacaatgccacttggctatgtaacacatggcttaaatttggaagaagctgctcggtatatgagatctctcaaagtgccagctacagtttctgtttcttcacctgatgctgttaca

gcgtataatggttatcttacttcttcttctaaaacacctgaagaacattttattgaaaccatctcacttgctggttcctataaagattggtcctattctggacaatctacacaactagg

tatagaatttcttaagagaggtgataaaagtgtatattacactagtaatcctaccacattccacctagatggtgaagttatcacctttgacaatcttaagacacttattctttgaga

gaagtgaggactattaaggtgtttacaacagtagacaacattaacctccacacgcaagttgtggacatgtcaatgacatatggacaacagtttggtccaacttatttggatgg

agctgatgttactaaaataaaacctcataattcacatgaaggtaaaacattttatgttttacctaatgatgacactctacgtgttgaggcttttgagtactaccacacaactgatcct

agttttctgggtaggtacatgtcagcattaaatcacactaaaaagtggaaatacccacaagttaatggtttaacttctattaaatgggcagataacaactgttatcttgccactgc

attgttaacactccaacaaatagagttgaagtttaatccacctgctctacaagatgcttattacagagcaagggctggtgaagctgctaacttttgtgcacttatcttagcctact

gtaataagacagtaggtgagttaggtgatgttagagaaacaatgagttacttgtttcaacatgccaatttagattcttgcaaaagagtcttgaacgtggtgtgtaaaacttgtgg

acaacagcagacaacccttaagggtgtagaagctgttatgtacatgggcacactttcttatgaacaatttaagaaaggtgttcagataccttgtacgtgtggtaaacaagctac

aaaatatctagtacaacaggagtcaccttttgttatgatgtcagcaccacctgctcagtatgaacttaagcatggtacatttacttgtgctagtgagtacactggtaattaccagt

gtggtcactataaacatataacttctaaagaaactttgtattgcatagacggtgattacttacaaagtcctcagaatacaaaggtcctattacggatgttttctacaaagaaaac

agttacacaacaaccataaaaccagttacttataaattggatggtgttgtttgtacagaaattgaccctaagttggacaattattataagaaagacaattcttatttcacagagca

accaattgatcttgtaccaaaccaaccatatccaaacgcaagcttcgataattttaagtttgtatgtgataatatcaaatttgctgatgatttaaaccagttaactggttataagaaa

cctgcttcaagagagcttaaagttacatttttccctgacttaaatggtgatgtggtggctattgattataaacactacacaccctatttaagaaaggagctaaattgttacataaa

cctattgtttggcatgttaacaatgcaactaataaagccacgtataaaccaaatacctggtgtatacgttgtctttggagcacaaaaccagttgaaacatcaaattcgtttgatgt

actgaagtcagaggacgcgcagggaatggataatcttgcctgcgaagatctaaaaccagtactgaagaagtagtggaaaatcctaccatacagaaagacgttcttgagt

gtaatgtgaaaactaccgaagttgtaggagacattatacttaaaccagcaaataatagtttaaaaattacagaagaggttggccacacagatctaatggctgcttatgtagac

aattctagtcttactattaagaaacctaatgaattatctagagtattaggtttgaaaacccttgctactcatggtttagctgctgttaatagtgtcccttgggatactatagctaattat

gctaagccttttcttaacaaagttgttagtacaactactaacatagttacacggtgtttaaaccgtgtttgtactaattatatgccttatttattactttattgctacaattgtgtactttt

actagaagtacaaattctagaattaaagcatctatgccgactactatagcaaagaatactgttaagagtgtcggtaaattttgtctagaggcttcatttaattatttgaagtcacct

aatttttctaaactgataaatattataatttggtttttactattaagtgtttgcctaggttctttaatctactcaaccgctgctttaggtgttttaatgtctaatttaggcatgccttcttact

gtactggttacagagaaggctatttgaactctactaatgtcactattgcaacctactgtactggttctataccttgtagtgtttgtcttagtggtttagattattagacacctatcctt

ctttagaaactatacaaattaccatttcatcttttaaatgggatttaactgatttggcttagttgcagagtggtttttggcatatattatttcactaggtttttctatgtacttggattgg

ctgcaatcatgcaattgtttttcagctattttgcagtacattttattagtaattcttggcttatgtggttaataattaatcttgtacaaatggccccgatttcagctatggttagaatgta

catcttctttgcatcattttattatgtatggaaaagttatgtgcatgttgtagacggttgtaattcatcaacttgtatgatgtgttacaaacgtaatagagcaacaagagtcgaatgt

acaactattgttaatggtgttagaaggtccttttatgtctatgctaatggaggtaaaggcttttgcaaactacacaattggaattgtgttaattgtgatacattctgtgctggtagta

catttattagtgatgaagttgcgagagacttgtcactacagtttaaaagaccaataaatcctactgaccagtcttcttacatcgttgatagtgttacagtgaagaatggttccatcc

atctttactttgataaagctggtcaaaagacttatgaaagacattctctctctcattttgttaacttagacaacctgagagctaataacactaaaggttcattgcctattaatgttata

gtttttgatggtaaatcaaaatgtgaagaatcatctgcaaaatcagcgtctgtttactacagtcagcttatgtgtcaacctatactgttactagatcaggcattagtgtctgatgttg

gtgatagtgcggaagttgcagttaaaatgtttgatgcttacgttaatacgttttcatcaacttttaacgtaccaatggaaaaactcaaaacactagttgcaactgcagaagctga

acttgcaaagaatgtgtccttagacaatgtcttatctacttttatttcagcagctcggcaagggtttgttgattcagatgtagaaactaaagatgttgttgaatgtcttaaattgtca

catcaatctgacatagaagttactggcgatagttgtaataactatatgctcacctataacaaagttgaaaacatgacaccccgtgaccttggtgcttgtattgactgtagtgcgc

gtcatattaatgcgcaggtagcaaaaagtcacaacattgctttgatatggaacgttaaagatttcatgtcattgtctgaacaactacgaaaacaaatacgtagtgctgctaaaa

agaataacttaccttttaagttgacatgtgcaactactagacaagttgttaatgttgtaacaacaaagatagcacttaagggtggtaaaattgttaataattggttgaagcagtta

attaaagttacacttgtgttcctttttgttgctgctattttctatttaataacacctgttcatgtcatgtctaaacatactgacttttcaagtgaaatcataggatacaaggctattgatg

gtggtgtcactcgtgacatagcatctacagatacttgttttgctaacaaacatgctgattttgacacatggtttagccagcgtggtggtagttatactaatgacaaagcttgccca

ttgattgctgcagtcataacaagagaagtgggttttgtcgtgcctggtttgcctggcacgatattacgcacaactaatggtgactttttgcatttcttacctagagtttttagtgca

gttggtaacatctgttacacaccatcaaaacttatagagtacactgactttgcaacatcagcttgtgttttggctgctgaatgtacaatttttaaagatgcttctggtaagccagta

ccatattgttatgataccaatgtactagaaggttctgttgcttatgaaagtttacgccctgacacacgttatgtgctcatggatggctctattattcaatttcctaacacctaccttga

aggttctgttagagtggtaacaacttttgattctgagtactgtaggcacggcacttgtgaaagatcagaagctggtgtttgtgtatctactagtggtagatgggtacttaacaat

gattattacagatattaccaggagttttctgtggtgtagatgctgtaaatttacttactaatatgtttacaccactaattcaacctattggtgattggacatatcagcatctatagta

gctggtggtattgtagctatcgtagtaacatgccttgcctactattttatgaggtttagaagagcttttggtgaatacagtcatgtagttgcctttaatactttactattccttatgtcat

tcactgtactagtttaacaccagtttactcattcttacctggtgtttattctgttatttacttgtacttgacattttatcttactaatgatgtttcttttttagcacatattcagtggatggtt

atgttcacacctttagtacctttctggataacaattgcttatatcatttgtatttccacaaagcatttctattggttctttagtaattacctaaagagacgtgtagtattaatggtgtttcct

ttagtacttttgaagaagctgcgctgtgcacctttttgttaaataaagaaatgtatctaaagttgcgtagtgatgtgctattacctcttacgcaatataatagatacttagctctttata

ataagtacaagtattttagtggagcaatggatacaactagctacagagaagctgcttgttgtcatctcgcaaaggctctcaatgacttcagtaactcaggttctgatgttctttac

caaccaccacaaacctctatcacctcagctgttttgcagagtggttttagaaaaatggcattcccatctggtaaagttgagggttgtatggtacaagtaacttgtggtacaacta

cacttaacggtattggcttgatgacgtagtttactgtccaagacatgtgatctgcacctctgaagacatgcttaaccctaattatgaagatttactcattcgtaagtctaatcataa

tttcttggtacaggctggtaatgttcaactcagggttattggacattctatgcaaaattgtgtacttaagcttaaggttgatacagccaatcctaagacacctaagtataagtttgtt

cgcattcaaccaggacagactttttcagtgttagcttgttacaatggttcaccatctggtgtttaccaatgtgctatgaggcccaatttcactattaagggttcattccttaatggtt

catgtggtagtgttggttttaacatagattatgactgtgtctattttgttacatgcaccatatggaattaccaactggagttcatgctggcacagacttagaaggtaacttttatgg

accttttgttgacaggcaaacagcacaagcagctggtacggacacaactattacagttaatgttttagcttggttgtacgctgctgttataaatggagacaggtggtttctcaat

cgatttaccacaactcttaatgactttaaccttgtggctatgaagtacaattatgaacctctaacacaagaccatgttgacatactaggacctattctgctcaaactggaattgc

cgttttagatatgtgtgcttcattaaaagaattactgcaaaatggtatgaatggacgtaccatattgggtagtgattattagaagatgaatttacaccttttgatgttgttagacaat

gctcaggtgttactttccaaagtgcagtgaaaagaacaatcaagggtacacaccactggttgttactcacaattttgacttcacttttagttttagtccagagtactcaatggtctt

tgttatttttttgtatgaaaatgcctttttaccttttgctatgggtattattgctatgtctgatttgcaatgatgtttgtcaaacataagcatgcatttactgtttgtttttgttaccttctct

tgccactgtagcttattttaatatggtctatatgcctgctagttgggtgatgcgtattatgacatggttggatatggttgatactagtttgtaggttttaagctaaaagactgtgttat

gtatgcatcagctgtagtgttactaatccttatgacagcaagaactgtgtatgatgatggtgctaggagagtgtggacacttatgaatgtcttgacactcgtttataaagtttatta

tggtaatgattagatcaagccatttccatgtgggctcttataatctctgttacttctaactactcaggtgtagttacaactgtcatgtttttggccagaggtattgtttttatgtgtgtt

gagtattgccctattttcttcataactggtaatacacttcagtgtataatgctagtttattgtttcttaggctatttttgtacttgttactttggcctatttgtttactcaaccgctactttag

actgactcttggtgtttatgattacttagtttctacacaggagtttagatatatgaattcacagggactactcccacccaagaatagcatagatgccttcaaactcaacattaaatt

gttgggtgttggtggcaaaccttgtatcaaagtagccactgtacagtctaaaatgtcagatgtaaagtgcacatcagtagtcttactctcagttttgcaacaactcagagtagaa

tcatcatctaaattgtgggctcaatgtgtccagttacacaatgacattctcttagctaaagatactactgaagcctttgaaaaaatggtttcactactttctgttttgattccatgca

gggtgctgtagacataaacaagattgtgaagaaatgctggacaacagggcaaccttacaagctatagcctcagagtttagttccdtccatcatatgcagcttttgctactgc

tcaagaagcttatgagcaggctgttgctaatggtgattctgaagttgttcttaaaaagttgaagaagtattgaatgtggctaaatctgaatttgaccgtgatgcagccatgcaa

cgtaagttggaaaagatggctgatcaagctatgacccaaatgtataaacaggctagatctgaggacaagagggcaaaagttactagtgctatgcagacaatgatttcacta

tgcttagaaagttggataatgatgcactcaacaacattatcaacaatgcaagagatggttgtgttccdtgaacataatacctcttacaacagcagccaaactaatggttgtcat

accagactataacacatataaaaatacgtgtgatggtacaacatttacttatgcatcagcattgtgggaaatccaacaggttgtagatgcagatagtaaaattgttcaacttagt

gaaattagtatggacaattcacctaatttagcatggcctcttattgtaacagctttaagggccaattctgctgtcaaattacagaataatgagcttagtcctgttgcactacgaca

gatgtcttgtgctgccggtactacacaaactgcttgcactgatgacaatgcgttagcttactacaacacaacaaagggaggtaggtttgtacttgcactgttatccgatttacag

gatttgaaatgggctagattccctaagagtgatggaactggtactatctatacagaactggaaccaccttgtaggtttgttacagacacacctaaaggtcctaaagtgaagtat

ttatactttattaaaggattaaacaacctaaatagaggtatggtacttggtagtttagctgccacagtacgtctacaagctggtaatgcaacagaagtgcctgccaattcaactg

tattatattctgtgatttgctgtagatgctgctaaagcttacaaagattatctagctagtgggggacaaccaatcactaattgtgttaagatgttgtgtacacacactggtactg

gtcaggcaataacagttacaccggaagccaatatggatcaagaatcctttggtggtgcatcgtgttgtctgtactgccgttgccacatagatcatccaaatcctaaaggatttt

gtgacttaaaaggtaagtatgtacaaatacctacaacttgtgctaatgaccctgtgggttttacacttaaaaacacagtagtaccgtctgcggtatgtggaaaggttatggctg

tagttgtgatcaactccgcgaacccatgcttcagtcagctgatgcacaatcgtttttaaacgggtttgcggtgtaagtgcagcccgtcttacaccgtgcggcacaggcactag

tactgatgtcgtatacagggcttttgacatctacaatgataaagtagctggttttgctaaattcctaaaaactaattgttgtcgcttccaagaaaaggacgaagatgacaatttaat

tgattcttactttgtagttaagagacacactttctctaactaccaacatgaagaaacaatttataatttacttaaggattgtccagagttgctaaacatgacttattaagtttagaat

agacggtgacatggtaccacatatatcacgtcaacgtcttactaaatacacaatggcagacctcgtctatgattaaggcattttgatgaaggtaattgtgacacattaaaaga

aatacttgtcacatacaattgttgtgatgatgattatttcaataaaaaggactggtatgattttgtagaaaacccagatatattacgcgtatacgccaacttaggtgaacgtgtac

gccaagattgttaaaaacagtacaattctgtgatgccatgcgaaatgctggtattgttggtgtactgacattagataatcaagatctcaatggtaactggtatgatttcggtgatt

tcatacaaaccacgccaggtagtggagttcctgttgtagattcttattattcattgttaatgcctatattaaccttgaccagggctttaactgcagagtcacatgttgacactgactt

aacaaagccttacattaagtgggatttgttaaaatatgacttcacggaagagaggttaaaactattgaccgttattttaaatattgggatcagacataccacccaaattgtgtta

actgtttggatgacagatgcattctgcattgtgcaaactttaatgttttattctctacagtgttcccacctacaagttttggaccactagtgagaaaaatatttgttgatggtgttcca

tttgtagtttcaactggataccacttcagagagctaggtgttgtacataatcaggatgtaaacttacatagctctagacttagttttaaggaattacttgtgtatgctgctgaccctg

ctatgcacgctgcttctggtaatctattactagataaacgcactacgtgatttcagtagctgcacttactaacaatgttgatttcaaactgtcaaacccggtaattttaacaaag

acttctatgactttgctgtgtctaagggtttctttaaggaaggaagttctgttgaattaaaacacttcttctttgctcaggatggtaatgctgctatcagcgattatgactactatcgt

tataatctaccaacaatgtgtgatatcagacaactactatttgtagttgaagttgttgataagtactttgattgttacgatggtggctgtattaatgctaaccaagtcatcgtcaaca

acctagacaaatcagctggttttccatttaataaatggggtaaggctagactttattatgattcaatgagttatgaggatcaagatgcacttttcgcatatacaaaacgtaatgtca

tccctactataactcaaatgaatcttaagtatgccattagtgcaaagaatagagctcgcaccgtagctggtgtctctatctgtagtactatgaccaatagacagtttcatcaaaa

attattgaaatcaatagccgccactagaggagctactgtagtaattggaacaagcaaattctatggtggttggcacaacatgttaaaaactgtttatagtgatgtagaaaaccc

tcaccttatgggttgggattatcctaaatgtgatagagccatgcctaacatgcttagaattatggcctcacttgttcttgctcgcaaacatacaacgtgttgtagcttgtcacacc

gtttctatagattagctaatgagtgtgctcaagtattgagtgaaatggtcatgtgtggcggttcactatatgttaaaccaggtggaacctcatcaggagatgccacaactgctta

tgctaatagtgtttttaacatttgtcaagctgtcacggccaatgttaatgcacttttatctactgatggtaacaaaattgccgataagtatgtccgcaatttacaacacagactttat

gagtgtctctatagaaatagagatgttgacacagactttgtgaatgagttttacgcatatttgcgtaaacatttctcaatgatgatactctctgacgatgctgttgtgtgtttcaata

gcacttatgcatctcaaggtctagtggctagcataaagaactttaagtcagttctttattatcaaaacaatgtttttatgtctgaagcaaaatgttggactgagactgaccttacta

aaggacctcatgaattttgctctcaacatacaatgctagttaaacagggtgatgattatgtgtaccttccttacccagatccatcaagaatcctaggggccggctgttttgtagat

gatatcgtaaaaacagatggtacacttatgattgaacggttcgtgtattagctatagatgcttacccacttactaaacatcctaatcaggagtatgctgatgtattcatttgtactt

acaatacataagaaagctacatgatgagttaacaggacacatgttagacatgtattctgttatgcttactaatgataacacttcaaggtattgggaacctgagt-tttatgaggcta

tgtacacaccgcatacagtcttacaggctgttggggcttgtgttctttgcaattcacagacttcattaagatgtggtgcttgcatacgtagaccattcttatgttgtaaatgctgtta

cgaccatgtcatatcaacatcacataaattagtcttgtagttaatccgtatgtttgcaatgaccaggttgtgatgtcacagatgtgactcaactttacttaggaggtatgagctat

tattgtaaatcacataaaccacccattagttttccattgtgtgctaatggacaagtttttggtttatataaaaatacatgtgttggtagcgataatgttactgactttaatgcaattgca

acatgtgactggacaaatgctggtgattacattttagctaacacctgtactgaaagactcaagctttttgcagcagaaacgctcaaagctactgaggagacatttaaactgtctt

atggtattgctactgtacgtgaagtgctgtctgacagagaattacatctttcatgggaagttggtaaacctagaccaccacttaaccgaaattatgtctttactggttatcgtgta

actaaaaacagtaaagtacaaataggagagtacacctttgaaaaaggtgactatggtgatgctgttgtttaccgaggtacaacaacttacaaattaaatgttggtgattattttgt

gctgacatcacatacagtaatgccattaagtgcacctacactagtgccacaagagcactatgttagaattactggcttatacccaacactcaatatctcagatgagttttctagc

aatgttgcaaattatcaaaaggttggtatgcaaaagtattctacactccagggaccacctggtactggtaagagtcattttgctattggcctagctctctactacccttctgctcg

catagtgtatacagcttgactcatgccgctgttgatgcactatgtgagaaggcattaaaatatttgcctatagataaatgtagtagaattatacctgcacgtgctcgtgtagagt

gttttgataaattcaaagtgaattcaacattagaacagtatgtatttgtactgtaaatgcattgcctgagacgacagcagatatagttgtattgatgaaatttcaatggccacaa

attatgatttgagtgttgtcaatgccagattacgtgctaagcactatgtgtacattggcgaccctgctcaattacctgcaccacgcacattgctaactaagggcacactagaac

cagaatatttcaattcagtgtgtagacttatgaaaactataggtccagacatgttcctcggaacttgtcggcgttgtcctgctgaaattgttgacactgtgagtgctttggtttatg

ataataagcttaaagcacataaagacaaatcagctcaatgctttaaaatgttttataagggtgttatcacgcatgatgtttcatctgcaattaacaggccacaaataggcgtggt

aagagaattccttacacgtaaccctgcttggagaaaagagtctttatttcaccttataattcacagaatgctgtagcctcaaagattttgggactaccaactcaaactgttgattc

atcacagggctcagaatatgactatgtcatattcactcaaaccactgaaacagctcactcttgtaatgtaaacagatttaatgttgctattaccagagcaaaagtaggcatacttt

gcataatgtctgatagagacctttatgacaagttgcaatttacaagtcttgaaattccacgtaggaatgtggcaactttacaagctgaaaatgtaacaggactctttaaagattgt

agtaaggtaatcactgggttacatcctacacaggcacctacacacctcagtgttgacactaaattcaaaactgaaggtttatgtgttgacatacctggcatacctaaggacatg

acctatagaagactcatctctatgatgggttttaaaatgaattatcaagttaatggttaccctaacatgtttatcacccgcgaagaagctataagacatgtacgtgcatggattgg

cttcgatgtcgaggggtgtcatgctactagagaagctgttggtaccaatttacctttacagctaggtttttctacaggtgttaacctagttgctgtacctacaggttatgttgatac

acctaataatacagatttttccagagttagtgctaaaccaccgcctggagatcaatttaaacacctcataccacttatgtacaaaggacttccttggaatgtagtgcgtataaag

attgtacaaatgttaagtgacacacttaaaaatctactgacagagtcgtatttgtcttatgggcacatggctttgagttgacatctatgaagtattttgtgaaaataggacctgag

cgcacctgttgtctatgtgatagacgtgccacatgcttttccactgcttcagacacttatgcctgttggcatcattctattggatttgattacgtctataatccgtttatgattgatgtt

caacaatggggttttacaggtaacctacaaagcaaccatgatctgtattgtcaagtccatggtaatgcacatgtagctagttgtgatgcaatcatgactaggtgtctagctgtcc

acgagtgattgttaagcgtgttgactggactattgaatatcctataattggtgatgaactgaagattaatgcggcttgtagaaaggttcaacacatggttgttaaagctgcatta

ttagcagacaaattcccagttcttcacgacattggtaaccctaaagctattaagtgtgtacctcaagctgatgtagaatggaagttctatgatgcacagccttgtagtgacaaa

gcttataaaatagaagaattattctattcttatgccacacattctgacaaattcacagatggtgtatgcctattttggaattgcaatgtcgatagatatcctgctaattccattgtttgt

agatttgacactagagtgctatctaaccttaacttgcctggttgtgatggtggcagtttgtatgtaaataaacatgcattccacacaccagcttttgataaaagtgatttgttaattt

aaaacaattaccatttttctattactctgacagtccatgtgagtctcatggaaaacaagtagtgtcagatatagattatgtaccactaaagtagctacgtgtataacacgttgcaa

tttaggtggtgctgtctgtagacatcatgctaatgagtacagattgtatctcgatgcttataacatgatgatctcagctggctttagcttgtgggtttacaaacaatttgatacttata

acctaggaacacttttacaagacttcagagtttagaaaatgtggcttttaatgttgtaaataagggacactttgatggacaacagggtgaagtaccagtttctatcattaataac

actgtttacacaaaagttgatggtgttgatgtagaattgtttgaaaataaaacaacattacctgttaatgtagcatttgagctttgggctaagcgcaacattaaaccagtaccaga

ggtgaaaatactcaataatttgggtgtggacattgctgctaatactgtgatctgggactacaaaagagatgctccagcacatatatctactattggtgtttgttctatgactgaca

tagccaagaaaccaactgaaacgatttgtgcaccactcactgtcttttttgatggtagagttgatggtcaagtagacttatttagaaatgcccgtaatggtgttcttattacagaa

ggtagtgttaaaggtttacaaccatctgtaggtcccaaacaagctagtcttaatggagtcacattaattggagaagccgtaaaaacacagttcaattattataagaaagttgat

ggtgttgtccaacaattacctgaaacttactttactcagagtagaaatttacaagaatttaaacccaggagtcaaatggaaattgatttcttagaattagctatggatgaattcatt

gaacggtataaattagaaggctatgccttcgaacatatcgtttatggagattttagtcatagtcagttaggtggtttacatctactgattggactagctaaacgttttaaggaatca

catttgaattagaagattttattcctatggacagtacagttaaaaactatttcataacagatgcgcaaacaggttcatctaagtgtgtgtgttctgttattgatttattacttgatgatt

ttgttgaaataataaaatcccaagatttatctgtagtttctaaggttgtcaaagtgactattgactatacagaaatttcatttatgattggtgtaaagatggccatgtagaaacatttt

acccaaaattacaatctagtcaagcgtggcaaccgggtgttgctatgcctaatattacaaaatgcaaagaatgctattagaaaagtgtgaccttcaaaattatggtgatagtg

caacattacctaaaggcataatgatgaatgtcgcaaaatatactcaactgtgtcaatatttaaacacattaacattagctgtaccctataatatgagagttatacattttggtgctg

gttctgataaaggagttgcaccaggtacagctgttttaagacagtggttgcctacgggtacgctgcttgtcgattcagatcttaatgactttgtctctgatgcagattcaactttg

attggtgattgtgcaactgtacatacagctaataaatgggatctcattattagtgatatgtacgaccctaagactaaaaatgttacaaaagaaaatgactctaaagagggtttttt

cacttacatttgtgggtttatacaacaaaagctagctcttggaggttccgtggctataaagataacagaacattcttggaatgctgatctttataagctcatgggacacttcgcat

ggtggacagcctttgttactaatgtgaatgcgtcatcatctgaagcatttttaattggatgtaattatcttggcaaaccacgcgaacaaatagatggttatgtcatgcatgcaaat

tacatattttggaggaatacaaatccaattcagttgtcttcctattctttatttgacatgagtaaatttccccttaaattaaggggtactgctgttatgtattaaaagaaggtcaaatc

aatgatatgattttatctcttcttagtaaaggtagacttataattagagaaaacaacagagttgttatttctagtgatgttcttgttaacaactaaacgaacaatgtttgtttttcttgttt

tattgccactagtctctagtcagtgtgttaatcttacaaccagaactcaattaccccctgcatacactaattattcacacgtggtgtttattaccctgacaaagttttcagatcctca

gttttacattcaactcaggacttgttcttacctttatttccaatgttacttggttccatgctatacatgtctctgggaccaatggtactaagaggtttgataaccctgtcctaccattta

atgatggtgtttattttgcttccactgagaagtctaacataataagaggctggatttttggtactactttagattcgaagacccagtccctacttattgttaataacgctactaatgtt

gttattaaagtctgtgaatttcaattttgtaatgatccatttttgggtgtttattaccacaaaaacaacaaaagttggatggaaagtgagttcagagtttattctagtgcgaataattg

cacttttgaatatgtactcagccttttcttatggaccttgaaggaaaacagggtaatttcaaaaatcttagggaatttgtgtttaagaatattgatggttattttaaaatatattctaa

gcacacgcctattaatttagtgcgtgatctccctcagggtttttcggctttagaaccattggtagatttgccaataggtattaacatcactaggtttcaaactttacttgctttacata

gaagttatttgactcctggtgattcttcttcaggttggacagaggtgctgcagcttattatgtgggttatcttcaacctaggacttttctattaaaatataatgaaaatggaaccatt

acagatgctgtagactgtgcacttgaccctctctcagaaacaaagtgtacgttgaaatccttcactgtagaaaaaggaatctatcaaacttctaactttagagtccaaccaaca

gaatctattgttagatttcctaatattacaaacttgtgccatttggtgaagtttttaacgccaccagatttgcatctgtttatgcttggaacaggaagagaatcagcaactgtgttg

ctgattattctgtcctatataattccgcatcattttccacttttaagtgttatggagtgtctcctactaaattaaatgatactgattactaatgtctatgcagattcatttgtaattagag

gtgatgaagtcagacaaatcgctccagggcaaactggaaagattgctgattataattataaattaccagatgattttacaggctgcgttatagcttggaattctaacaatcttgat

tctaaggttggtggtaattataattacctgtatagattgtttaggaagtctaatctcaaaccttttgagagagatatttcaactgaaatctatcaggccggtagcacaccttgtaat

ggtgttgaaggttttaattgttactttcctttacaatcatatggtttccaacccactaatggtgttggttaccaaccatacagagtagtagtactttatttgaacttctacatgcacca

gcaactgtttgtggacctaaaaagtctactaatttggttaaaaacaaatgtgtcaatttcaacttcaatggtttaacaggcacaggtgttcttactgagtctaacaaaaagtttctg

cattccaacaatttggcagagacattgctgacactactgatgctgtccgtgatccacagacacttgagattcttgacattacaccatgttatttggtggtgtcagtgttataaca

ccaggaacaaatacttctaaccaggttgctgttattatcaggatgttaactgcacagaagtccctgttgctattcatgcagatcaacttactcctacttggcgtgtttattctaca

ggttctaatgtttttcaaacacgtgcaggctgtttaataggggctgaacatgtcaacaactcatatgagtgtgacatacccattggtgcaggtatatgcgctagttatcagactc

agactaattctcctcggcgggcacgtagtgtagctagtcaatccatcattgcctacactatgtcacttggtgcagaaaattcagttgcttactctaataactctattgccataccc

acaaattttactattagtgttaccacagaaattctaccagtgtctatgaccaagacatcagtagattgtacaatgtacatttgtggtgattcaactgaatgcagcaatcttttgttgc

aatatggcagtttttgtacacaattaaaccgtgattaactggaatagctgttgaacaagacaaaaacacccaagaagtttttgcacaagtcaaacaaatttacaaaacaccac

caattaaagattttggtggttttaatttttcacaaatattaccagatccatcaaaaccaagcaagaggtcatttattgaagatctacttttcaacaaagtgacacttgcagatgctg

gcttcatcaaacaatatggtgattgccttggtgatattgctgctagagacctcatttgtgcacaaaagtttaacggccttactgttttgccacctttgctcacagatgaaatgattg

ctcaatacacttctgcactgttagcgggtacaatcacttctggttggacctttggtgcaggtgctgcattacaaataccatttgctatgcaaatggcttataggtttaatggtattg

gagttacacagaatgttctctatgagaaccaaaaattgattgccaaccaatttaatagtgctattggcaaaattcaagactcactttcttccacagcaagtgcacttggaaaactt

caagatgtggtcaaccaaaatgcacaagctttaaacacgcttgttaaacaacttagctccaattttggtgcaatttcaagtgttttaaatgatatcctttcacgtcttgacaaagtt

gaggctgaagtgcaaattgataggttgatcacaggcagacttcaaagtttgcagacatatgtgactcaacaattaattagagctgcagaaatcagagcttctgctaatcttgct

gctactaaaatgtcagagtgtgtacttggacaatcaaaaagagttgatttttgtggaaagggctatcatcttatgtccttccctcagtcagcacctcatggtgtagtcttcttgcat

gtgacttatgtccctgcacaagaaaagaacttcacaactgctcctgccatttgtcatgatggaaaagcacactttcctcgtgaaggtgtctttgtttcaaatggcacacactggt

ttgtaacacaaaggaatttttatgaaccacaaatcattactacagacaacacatttgtgtaggtaactgtgatgttgtaataggaattgtcaacaacacagtttatgatcct-ttgc

aacctgaattagactcattcaaggaggagttagataaatattttaagaatcatacatcaccagatgttgatttaggtgacatctctggcattaatgcttcagttgtaaacattcaaa

aagaaattgaccgcctcaatgaggttgccaagaatttaaatgaatctctcatcgatctccaagaacttggaaagtatgagcagtatataaaatggccatggtacatttggctag

gttttatagaggcttgattgccatagtaatggtgacaattatgctttgctgtatgaccagttgctgtagttgtctcaagggctgttgttcttgtggatcctgctgcaaatttgatgaa

gacgactctgagccagtgctcaaaggagtcaaattacattacacataaacgaacttatggatttgtttatgagaatcttcacaattggaactgtaactttgaagcaaggtgaaat

caaggatgctactccttcagattttgttcgcgctactgcaacgataccgatacaagcctcactccctttcggatggcttattgttggcgttgcacttcttgctgtttttcagagcgc

ttccaaaatcataaccctcaaaaagagatggcaactagcactctccaagggtgttcactttgtttgcaacttgctgttgttgtttgtaacagtttactcacaccttttgctcgttgct

gctggccttgaagccccttttctctatctttatgctttagtctacttcttgcagagtataaactttgtaagaataataatgaggctttggctttgctggaaatgccgttccaaaaacc

cattactttatgatgccaactattttctttgctggcatactaattgttacgactattgtataccttacaatagtgtaacttcttcaattgtcattacttcaggtgatggcacaacaagtcc

tatttctgaacatgactaccagattggtggttatactgaaaaatgggaatctggagtaaaagactgtgttgtattacacagttacttcacttcagactattaccagctgtactcaac

tcaattgagtacagacactggtgttgaacatgttaccttcttcatctacaataaaattgttgatgagcctgaagaacatgtccaaattcacacaatcgacggttcatccggagtt

gttaatccagtaatggaaccaatttatgatgaaccgacgacgactactagcgtgcctttgtaagcacaagctgatgagtacgaacttatgtactcattcgtttcggaagagaca

ggtacgttaatagttaatagcgtacttattttcttgattcgtggtattcttgctagttacactagccatccttactgcgcttcgattgtgtgcgtactgctgcaatattgttaacgtga

gtcttgtaaaaccttattttacgtttactdcgtgttaaaaatctgaattcttctagagttcctgatcttctggtctaaacgaactaaatattatattagtttttctgtttggaactttaattt

tagccatggcagattccaacggtactattaccgttgaagagcttaaaaagctccttgaacaatggaacctagtaataggtttcctattccttacatggatttgtcttctacaatttg

cctatgccaacaggaataggtttttgtatataattaagttaattttcctaggctgttatggccagtaactttagcttgttttgtgcttgctgctgtttacagaataaattggatcaccg

gtggaattgctatcgcaatggcttgtcttgtaggcttgatgtggctcagctacttcattgcttctttcagactgtttgcgcgtacgcgttccatgtggtcattcaatccagaaacta

acattcttctcaacgtgccactccatggcactattctgaccagaccgcttctagaaagtgaactcgtaatcggagctgtgatccttcgtggacatcttcgtattgctggacacca

tctaggacgctgtgacatcaaggacctgcctaaagaaatcactgttgctacatcacgaacgctttcttattacaaattgggagcttcgcagcgtgtagcaggtgactcaggttt

tgctgcatacagtcgctacaggattggcaactataaattaaacacagaccattccagtagcagtgacaatattgattgcttgtacagtaagtgacaacagatgtttcatctcgt

tgactttcaggttactatagcagagatattactaattattatgaggacttttaaagtttccatttggaatcttgattacatcataaacctcataattaaaaatttatctaagtcactaact

gagaataaatattctcaattagatgaagagcaaccaatggagattgattaaacgaacatgaaaattattcttttcttggcactgataacactcgctacttgtgagattatcactac

caagagtgtgttagaggtacaacagtacttttaaaagaaccttgacttctggaacatacgagggcaattcaccatttcatcctctagctgataacaaatttgcactgacttgctt

tagcactcaatttgatttgcttgtcctgacggcgtaaaacacgtctatcagttacgtgccagatcagtttcacctaaactgttcatcagacaagaggaagttcaagaactttact

ctccaatttttcttattgttgcggcaatagtgtttataacactttgatcacactcaaaagaaagacagaatgattgaactttcattaattgacttctatttgtgattttagcctttctgc

tattccttgttttaattatgcttattatcttttggttctcacttgaactgcaagatcataatgaaacttgtcacgcctaaacgaacatgaaatttcttgttttcttaggaatcatcacaact

gtagctgcatttcaccaagaatgtagtttacagtcatgtactcaacatcaaccatatgtagttgatgacccgtgtcctattcacttctattctaaatggtatattagagtaggagct

agaaaatcagcacctttaattgaattgtgcgtggatgaggctggttctaaatcacccattcagtacatcgatatcggtaattatacagtttcctgtttaccttttacaattaattgcc

aggaacctaaattgggtagtcttgtagtgcgttgttcgttctatgaagactttttagagtatcatgacgttcgtgttgttttagatttcatctaaacgaacaaactaaaatgtctgata

atggaccccaaaatcagcgaaatgcaccccgcattacgtttggtggaccdcagattcaactggcagtaaccagaatggagaacgcagtggggcgcgatcaaaacaac

gtcggccccaaggtttacccaataatactgcgtcttggttcaccgctctcactcaacatggcaaggaagaccttaaattccctcgaggacaaggcgttccaattaacaccaat

agcagtccagatgaccaaattggctactaccgaagagctaccagacgaattcgtggtggtgacggtaaaatgaaagatctcagtccaagatggtatttctactacctagga

actgggccagaagctggacttccctatggtgctaacaaagacggcatcatatgggttgcaactgagggagccttgaatacaccaaaagatcacattggcacccgcaatcc

tgctaacaatgctgcaatcgtgctacaacttcctcaaggaacaacattgccaaaaggcttctacgcagaagggagcagaggcggcagtcaagcctcttctcgttcctcatc

acgtagtcgcaacagttcaagaaattcaactccaggcagcagtaggggaacttctcctgctagaatggctggcaatggcggtgatgctgctcttgattgctgctgcttgac

agattgaaccagcttgagagcaaaatgtaggtaaaggccaacaacaacaaggccaaactgtcactaagaaatctgctgctgaggcttctaagaagcctcggcaaaaac

gtactgccactaaagcatacaatgtaacacaagattcggcagacgtggtccagaacaaacccaaggaaattttggggaccaggaactaatcagacaaggaactgattac

aaacattggccgcaaattgcacaatttgcccccagcgcttcagcgttcttcggaatgtcgcgcattggcatggaagtcacaccttcgggaacgtggttgacctacacaggtg

ccatcaaattggatgacaaagatccaaatttcaaagatcaagtcattttgctgaataagcatattgacgcatacaaaacattcccaccaacagagcctaaaaaggacaaaaa

gaagaaggctgatgaaactcaagccttaccgcagagacagaagaaacagcaaactgtgactatcttcctgctgcagatttggatgatttctccaaacaattgcaacaatcc

atgagcagtgctgactcaactcaggcctaaactcatgcagaccacacaaggcagatgggctatataaacgttttcgcttttccgtttacgatatatagtctactcttgtgcagaa

tgaattctcgtaactacatagcacaagtagatgtagttaactttaatctcacatagcaatctttaatcagtgtgtaacattagggaggacttgaaagagccaccacattttcaccg

aggccacgcggagtacgatcgagtgtacagtgaacaatgctagggagagctgcctatatggaagagccctaatgtgtaaaattaattttagtagtgctatccccatgtgattt

taatagcttcttaggagaatgacaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa

2408
SARS-CoV-
atattaggtttttacctacccaggaaaagccaaccaacctcgatctcttgtagatctgttctctaaacgaactttaaaatctgtgtagctgtcgctcggctgcatgcctagtgcac

1 genome
ctacgcagtataaacaataataaattttactgtcgttgacaagaaacgagtaactcgtccctcttctgcagactgcttacggtttcgtccgtgttgcagtcgatcatcagcatacc

(Genbank
taggtttcgtccgggtgtgaccgaaaggtaagatggagagccttgttcttggtgtcaacgagaaaacacacgtccaactcagtttgcctgtccttcaggttagagacgtgcta

Accession
gtgcgtggcttcggggactctgtggaagaggccctatcggaggcacgtgaacacctcaaaaatggcacttgtggtctagtagagctggaaaaaggcgtactgccccagc

No.
ttgaacagccctatgtgttcattaaacgttctgatgccttaagcaccaatcacggccacaaggtcgttgagctggttgcagaaatggacggcattcagtacggtcgtagcggt

NC_
ataacactgggagtactcgtgccacatgtgggcgaaaccccaattgcataccgcaatgttcttcttcgtaagaacggtaataagggagccggtggtcatagctatggcatc

004718.3)
gatctaaagtcttatgacttaggtgacgagcttggcactgatcccattgaagattatgaacaaaactggaacactaagcatggcagtggtgcactccgtgaactcactcgtga

gctcaatggaggtgcagtcactcgctatgtcgacaacaatttctgtggcccagatgggtaccctcttgattgcatcaaagattttctcgcacgcgcgggcaagtcaatgtgca

ctctttccgaacaacttgattacatcgagtcgaagagaggtgtctactgctgccgtgaccatgagcatgaaattgcctggttcactgagcgctctgataagagctacgagca

ccagacacccttcgaaattaagagtgccaagaaatttgacactttcaaaggggaatgcccaaagtttgtgtttcctcttaactcaaaagtcaaagtcattcaaccacgtgttga

aaagaaaaagactgagggtttcatggggcgtatacgctctgtgtaccctgttgcatctccacaggagtgtaacaatatgcacttgtctaccttgatgaaatgtaatcattgcga

tgaagtttcatggcagacgtgcgactttctgaaagccacttgtgaacattgtggcactgaaaatttagttattgaaggacctactacatgtgggtacctacctactaatgctgta

gtgaaaatgccatgtcctgcctgtcaagacccagagattggacctgagcatagtgttgcagattatcacaaccactcaaacattgaaactcgactccgcaagggaggtagg

actagatgttttggaggctgtgtgtttgcctatgttggctgctataataagcgtgcctactgggttcctcgtgctagtgctgatattggctcaggccatactggcattactggtga

caatgtggagaccttgaatgaggatctccttgagatactgagtcgtgaacgtgttaacattaacattgttggcgattttcatttgaatgaagaggttgccatcattttggcatcttt

ctctgcttctacaagtgcctttattgacactataaagagtcttgattacaagtattcaaaaccattgttgagtcctgcggtaactataaagttaccaagggaaagcccgtaaaag

gtgcttggaacattggacaacagagatcagttttaacaccactgtgtggttttccctcacaggctgctggtgttatcagatcaatttttgcgcgcacacttgatgcagcaaacca

ctcaattcctgatttgcaaagagcagctgtcaccatacttgatggtatttctgaacagtcattacgtcttgtcgacgccatggtttatacttcagacctgctcaccaacagtgtcat

tattatggcatatgtaactggtggtcttgtacaacagacttctcagtggttgtctaatcttttgggcactactgttgaaaaactcaggcctatctttgaatggattgaggcgaaact

tagtgcaggagttgaatttctcaaggatgcttgggagattctcaaatttctcattacaggtgtttttgacatcgtcaagggtcaaatacaggttgcttcagataacatcaaggatt

gtgtaaaatgcttcattgatgttgttaacaaggcactcgaaatgtgcattgatcaagtcactatcgctggcgcaaagttgcgatcactcaacttaggtgaagtcttcatcgctca

aagcaagggactttaccgtcagtgtatacgtggcaaggagcagctgcaactactcatgcctcttaaggcaccaaaagaagtaacctttcttgaaggtgattcacatgacaca

gtacttacctctgaggaggttgttctcaagaacggtgaactcgaagcactcgagacgcccgttgatagcttcacaaatggagctatcgttggcacaccagtagtgtaaatg

gcctcatgacttagagattaaggacaaagaacaatactgcgcattgtctcctggtttactggctacaaacaatgtattcgcttaaaagggggtgcaccaattaaaggtgtaa

cattggagaagatactgtttgggaagttcaaggttacaagaatgtgagaatcacatttgagcttgatgaacgtgttgacaaagtgcttaatgaaaagtgactgtctacactgt

tgaatccggtaccgaagttactgagtttgcatgtgttgtagcagaggctgttgtgaagactttacaaccagtttctgatctccttaccaacatgggtattgatcttgatgagtgga

gtgtagctacattctacttatttgatgatgctggtgaagaaaacttttcatcacgtatgtattgttccttttaccctccagatgaggaagaagaggacgatgcagagtgtgagga

agaagaaattgatgaaacctgtgaacatgagtacggtacagaggatgattatcaaggtaccactggaatttggtgcctcagctgaaacagttcgagttgaggaagaaga

agaggaagactggctggatgatactactgagcaatcagagattgagccagaaccagaacctacacctgaagaaccagttaatcagtttactggttatttaaaacttactgac

aatgttgccattaaatgtgttgacatcgttaaggaggcacaaagtgctaatcctatggtgattgtaaatgctgctaacatacacctgaaacatggtggtggtgtagcaggtgca

ctcaacaaggcaaccaatggtgccatgcaaaaggagagtgatgattacattaagctaaatggccctcttacagtaggagggtcttgtttgattctggacataatcttgctaag

aagtgtctgcatgttgttggacctaacctaaatgcaggtgaggacatccagcttcttaaggcagcatatgaaaatttcaattcacaggacatcttacttgcaccattgttgtcag

caggcatatttggtgctaaaccacttcagtattacaagtgtgcgtgcagacggttcgtacacaggtttatattgcagtcaatgacaaagctctttatgagcaggttgtcatgga

ttatcttgataacctgaagcctagagtggaagcacctaaacaagaggagccaccaaacacagaagattccaaaactgaggagaaatctgtcgtacagaagcctgtcgatg

tgaagccaaaaattaaggcctgcattgatgaggttaccacaacactggaagaaactaagtttcttaccaataagttactcttgtttgctgatatcaatggtaagattaccatgat

tctcagaacatgcttagaggtgaagatatgtctttccttgagaaggatgcaccttacatggtaggtgatgttatcactagtggtgatatcacttgtgttgtaataccctccaaaaa

ggctggtggcactactgagatgctctcaagagctttgaagaaagtgccagttgatgagtatataaccacgtaccctggacaaggatgtgctggttatacacttgaggaagct

aagactgctcttaagaaatgcaaatctgcattttatgtactaccttcagaagcacctaatgctaaggaagagattctaggaactgtatcctggaatttgagagaaatgcttgctc

atgctgaagagacaagaaaattaatgcctatatgcatggatgttagagccataatggcaaccatccaacgtaagtataaaggaattaaaattcaagagggcatcgttgactat

ggtgtccgattcttcttttatactagtaaagagcctgtagcttctattattacgaagctgaactctctaaatgagccgcttgtcacaatgccaattggttatgtgacacatggtttta

atcttgaagaggctgcgcgctgtatgcgttctcttaaagctcctgccgtagtgtcagtatcatcaccagatgctgttactacatataatggatacctcacttcgtcatcaaagac

atctgaggagcactttgtagaaacagtttattggctggctcttacagagattggtcctattcaggacagcgtacagagttaggtgttgaatttcttaagcgtggtgacaaaatt

gtgtaccacactctggagagccccgtcgagtttcatcttgacggtgaggttctttcacttgacaaactaaagagtctcttatccctgcgggaggttaagactataaaagtgttc

acaactgtggacaacactaatctccacacacagcttgtggatatgtctatgacatatggacagcagtttggtccaacatacttggatggtgctgatgttacaaaaattaaacct

catgtaaatcatgagggtaagactttattgtactacctagtgatgacacactacgtagtgaagattcgagtactaccatactcttgatgagagttttcttggtaggtacatgtct

gattaaaccacacaaagaaatggaaatttcctcaagttggtggtttaacttcaattaaatgggctgataacaattgttatttgtctagtgttttattagcacttcaacagcttgaagt

caaattcaatgcaccagcacttcaagaggcttattatagagcccgtgctggtgatgctgctaacttttgtgcactcatactcgcttacagtaataaaactgttggcgagcttggt

gatgtcagagaaactatgacccatcttctacagcatgctaatttggaatctgcaaagcgagttcttaatgtggtgtgtaaacattgtggtcagaaaactactaccttaacgggtg

tagaagctgtgatgtatatgggtactctatcttatgataatcttaagacaggtgtttccattccatgtgtgtgtggtcgtgatgctacacaatatctagtacaacaagagtcttctttt

gttatgatgtctgcaccacctgctgagtataaattacagcaaggtacattcttatgtgcgaatgagtacactggtaactatcagtgtggtcattacactcatataactgctaagga

gaccactatcgtattgacggagctcaccttacaaagatgtcagagtacaaaggaccagtgactgatgttttctacaaggaaacatcttacactacaaccatcaagcctgtgt

cgtataaactcgatggagttacttacacagagattgaaccaaaattggatgggtattataaaaaggataatgcttactatacagagcagcctatagaccttgtaccaactcaac

cattaccaaatgcgagttttgataatttcaaactcacatgttctaacacaaaatttgctgatgatttaaatcaaatgacaggcttcacaaagccagcttcacgagagctatctgtc

acattcttcccagacttgaatggcgatgtagtggctattgactatagacactattcagcgagtttcaagaaaggtgctaaattactgcataagccaattgtttggcacattaacc

aggctacaaccaagacaacgttcaaaccaaacacttggtgtttacgttgtctttggagtacaaagccagtagatacttcaaattcatttgaagttctggcagtagaagacacac

aaggaatggacaatcttgcttgtgaaagtcaacaacccacctctgaagaagtagtggaaaatcctaccatacagaaggaagtcatagagtgtgacgtgaaaactaccgaa

gttgtaggcaatgtcatacttaaaccatcagatgaaggtgttaaagtaacacaagagttaggtcatgaggatcttatggctgcttatgtggaaaacacaagcattaccattaag

aaacctaatgagctttcactagccttaggtttaaaaacaattgccactcatggtattgctgcaattaatagtgttccttggagtaaaattttggcttatgtcaaaccattcttaggac

aagcagcaattacaacatcaaattgcgctaagagattagcacaacgtgtgtttaacaattatatgccttatgtgtttacattattgttccaattgtgtacttttactaaaagtaccaat

tctagaattagagcttcactacctacaactattgctaaaaatagtgttaagagtgttgctaaattatgtttggatgccggcattaattatgtgaagtcacccaaattttctaaattgtt

cacaatcgctatgtggctattgttgttaagtatttgcttaggttactaatctgtgtaactgctgatttggtgtactcttatctaattttggtgctccttcttattgtaatggcgttagag

aattgtatcttaattcgtctaacgttactactatggatttctgtgaaggttatttccttgcagcatttgtttaagtggattagactcccttgattcttatccagctcttgaaaccattcag

gtgacgatttcatcgtacaagctagacttgacaattttaggtctggccgctgagtgggttttggcatatatgttgttcacaaaattatttatttattaggtctttcagctataatgca

ggtgttctttggctattttgctagtcatttcatcagcaattcttggctcatgtggtttatcattagtattgtacaaatggcacccgtttctgcaatggttaggatgtacatcttctttgctt

ctttctactacatatggaagagctatgttcatatcatggatggttgcacctcttcgacttgcatgatgtgctataagcgcaatcgtgccacacgcgttgagtgtacaactattgtt

aatggcatgaagagatctttctatgtctatgcaaatggaggccgtggcttctgcaagactcacaattggaattgtctcaattgtgacacattttgcactggtagtacattcattag

tgatgaagttgctcgtgatttgtcactccagtttaaaagaccaatcaaccctactgaccagtcatcgtatattgttgatagtgttgctgtgaaaaatggcgcgcttcacctctactt

tgacaaggctggtcaaaagacctatgagagacatccgctctcccattttgtcaatttagacaatttgagagctaacaacactaaaggttcactgcctattaatgtcatagtttttg

atggcaagtccaaatgcgacgagtctgcttctaagtctgcttctgtgtactacagtcagctgatgtgccaacctattctgttgcttgaccaagctcttgtatcagacgttggaga

tagtactgaagtttccgttaagatgtttgatgcttatgtcgacaccttttcagcaacttttagtgttcctatggaaaaacttaaggcacttgttgctacagctcacagcgagttagc

aaagggtgtagctttagatggtgtcctttctacattcgtgtcagctgcccgacaaggtgttgttgataccgatgttgacacaaaggatgttattgaatgtctcaaactttcacatc

actctgacttagaagtgacaggtgacagttgtaacaatttcatgctcacctataataaggttgaaaacatgacgcccagagatcttggcgcatgtattgactgtaatgcaagg

catatcaatgcccaagtagcaaaaagtcacaatgtttcactcatctggaatgtaaaagactacatgtctttatctgaacagctgcgtaaacaaattcgtagtgctgccaagaag

aacaacataccttttagactaacttgtgctacaactagacaggttgtcaatgtcataactactaaaatctcactcaagggtggtaagattgttagtacttgttttaaacttatgctta

aggccacattattgtgcgttcttgctgcattggtttgttatatcgttatgccagtacatacattgtcaatccatgatggttacacaaatgaaatcattggttacaaagccattcagga

tggtgtcactcgtgacatcatttctactgatgattgttttgcaaataaacatgctggttttgacgcatggtttagccagcgtggtggttcatacaaaaatgacaaaagctgccctg

tagtagctgctatcattacaagagagattggtttcatagtgcctggcttaccgggtactgtgctgagagcaatcaatggtgacttcttgcattttctacctcgtgtttttagtgctgt

tggcaacatttgctacacaccttccaaactcattgagtatagtgattttgctacctctgcttgcgttcttgctgctgagtgtacaatttttaaggatgctatgggcaaacctgtgcc

atattgttatgacactaatttgctagagggttctatttcttatagtgagcttcgtccagacactcgttatgtgcttatggatggttccatcatacagtttcctaacacttacctggagg

gttctgttagagtagtaacaacttttgatgctgagtactgtagacatggtacatgcgaaaggtcagaagtaggtatttgcctatctaccagtggtagatgggttcttaataatga

gcattacagagctctatcaggagttttctgtggtgttgatgcgatgaatctcatagctaacatctttactcctcttgtgcaacctgtgggtgattagatgtgtctgcttcagtagtg

gctggtggtattattgccatattggtgacttgtgctgcctactactttatgaaattcagacgtgtttttggtgagtacaaccatgttgttgctgctaatgcacttttgtttttgatgtcttt

cactatactagtaggtaccagcttacagctttctgccgggagtctactcagtatttacttgtacttgacattctatttcaccaatgatgtttcattcttggctcaccttcaatggttt

gccatgttttctcctattgtgcctttttggataacagcaatctatgtattctgtatttctctgaagcactgccattggttattaacaactatcttaggaaaagagtcatgtttaatgga

gttacatttagtaccttcgaggaggctgattgtgtacctttttgctcaacaaggaaatgtacctaaaattgcgtagcgagacactgttgccacttacacagtataacaggtatct

tgactatataacaagtacaagtatttcagtggagccttagatactaccagctatcgtgaagcagcttgctgccacttagcaaaggctctaaatgactttagcaactcaggtgct

gatgttactaccaaccaccacagacatcaatcacttctgctgttctgcagagtggttttaggaaaatggcattcccgtcaggcaaagttgaagggtgcatggtacaagtaac

ctgtggaactacaactcttaatggattgtggttggatgacacagtatactgtccaagacatgtcatttgcacagcagaagacatgcttaatcctaactatgaagatctgctcatt

cgcaaatccaaccatagctttcttgttcaggctggcaatgttcaacttcgtgttattggccattctatgcaaaattgtctgcttaggcttaaagttgatacttctaaccctaagacac

ccaagtataaatttgtccgtatccaacctggtcaaacattttcagttctagcatgctacaatggttcaccatctggtgtttatcagtgtgccatgagacctaatcataccattaaag

gttattccttaatggatcatgtggtagtgttggttttaacattgattatgattgcgtgtctttctgctatatgcatcatatggagcttccaacaggagtacacgctggtactgactta

gaaggtaaattctatggtccatttgttgacagacaaactgcacaggctgcaggtacagacacaaccataacattaaatgttttggcatggctgtatgctgctgttatcaatggt

gataggtggtttcttaatagattcaccactactttgaatgactttaaccttgtggcaatgaagtacaactatgaacctttgacacaagatcatgttgacatattgggacctctttctg

ctcaaacaggaattgccgtcttagatatgtgtgctgattgaaagagctgctgcagaatggtatgaatggtcgtactatccttggtagcactattttagaagatgagtttacacc

atttgatgttgttagacaatgactggtgttaccttccaaggtaagttcaagaaaattgttaagggcactcatcattggatgatttaactttcttgacatcactattgattcttgttca

aagtacacagtggtcactgtttttctttgtttacgagaatgattcttgccatttactcttggtattatggcaattgctgcatgtgctatgctgcttgttaagcataagcacgcattctt

gtgcttgtttctgttaccttctcttgcaacagttgcttactttaatatggtctacatgcctgctagctgggtgatgcgtatcatgacatggcttgaattggctgacactagcttgtctg

gttataggcttaaggattgtgttatgtatgcttcagctttagttttgcttattctcatgacagctcgcactgtttatgatgatgctgctagacgtgtttggacactgatgaatgtcatta

cacttgtttacaaagtctactatggtaatgattagatcaagctatttccatgtgggccttagttatttctgtaacctctaactattctggtgtcgttacgactatcatgtttttagctag

agctatagtgtttgtgtgtgttgagtattacccattgttatttattactggcaacaccttacagtgtatcatgcttgtttattgtttcttaggctattgttgctgctgctactttggccttttc

tgtttactcaaccgttacttcaggcttactcttggtgtttatgactacttggtactacacaagaatttaggtatatgaactcccaggggcttttgcctcctaagagtagtattgatg

ctttcaagcttaacattaagttgttgggtattggaggtaaaccatgtatcaaggttgctactgtacagtctaaaatgtctgacgtaaagtgcacatctgtggtactgctctcggttc

ttcaacaacttagagtagagtcatcttctaaattgtgggcacaatgtgtacaactccacaatgatattcttcttgcaaaagacacaactgaagctttcgagaagatggtttctcttt

tgtctgttttgctatccatgcagggtgctgtagacattaataggttgtgcgaggaaatgctcgataaccgtgctactcttcaggctattgcttcagaatttagttattaccatcata

tgccgcttatgccactgcccaggaggcctatgagcaggctgtagctaatggtgattctgaagtcgttctcaaaaagttaaagaaatctttgaatgtggctaaatctgagtttga

ccgtgatgctgccatgcaacgcaagttggaaaagatggcagatcaggctatgacccaaatgtacaaacaggcaagatctgaggacaagagggcaaaagtaactagtgc

tatgcaaacaatgctcttcactatgcttaggaagcttgataatgatgcacttaacaacattatcaacaatgcgcgtgatggttgtgttccactcaacatcataccattgactacag

cagccaaactcatggttgttgtccctgattatggtacctacaagaacacttgtgatggtaacacctttacatatgcatctgcactagggaaatccagcaagttgttgatgcgga

tagcaagattgttcaacttagtgaaattaacatggacaattcaccaaatttggcttggcctcttattgttacagctctaagagccaactcagctgttaaactacagaataatgaac

tgagtccagtagcactacgacagatgtcctgtgcggctggtaccacacaaacagcttgtactgatgacaatgcacttgcctactataacaattcgaagggaggtaggtttgt

gctggcattactatcagaccaccaagatctcaaatgggctagattccctaagagtgatggtacaggtacaatttacacagaactggaaccaccttgtaggtttgttacagaca

caccaaaagggcctaaagtgaaatacttgtacttcatcaaaggcttaaacaacctaaatagaggtatggtgctgggcagtttagctgctacagtacgtcttcaggctggaaat

gctacagaagtacctgccaattcaactgtgattccttctgtgatttgcagtagaccctgctaaagcatataaggattacctagcaagtggaggacaaccaatcaccaactgt

gtgaagatgttgtgtacacacactggtacaggacaggcaattactgtaacaccagaagctaacatggaccaagagtcctttggtggtgcttcatgttgtagtattgtagatgc

cacattgaccatccaaatcctaaaggattctgtgacttgaaaggtaagtacgtccaaatacctaccacttgtgctaatgacccagtgggttttacacttagaaacacagtagta

ccgtctgcggaatgtggaaaggttatggctgtagttgtgaccaactccgcgaacccttgatgcagtctgcggatgcatcaacgtttttaaacgggtttgcggtgtaagtgcag

cccgtcttacaccgtgcggcacaggcactagtactgatgtcgtctacagggcttttgatatttacaacgaaaaagttgctggttttgcaaagttcctaaaaactaattgctgtcg

cttccaggagaaggatgaggaaggcaatttattagactcttactttgtagttaagaggcatactatgtctaactaccaacatgaagagactatttataacttggttaaagattgtc

cagcggttgctgtccatgactttttcaagtttagagtagatggtgacatggtaccacatatatcacgtcagcgtctaactaaatacacaatggctgatttagtctatgctctacgt

cattttgatgagggtaattgtgatacattaaaagaaatactcgtcacatacaattgctgtgatgatgattatttcaataagaaggattggtatgacttcgtagagaatcctgacatc

ttacgcgtatatgctaacttaggtgagcgtgtacgccaatcattattaaagactgtacaattctgcgatgctatgcgtgatgcaggcattgtaggcgtactgacattagataatc

aggatcttaatgggaactggtacgatttcggtgatttcgtacaagtagcaccaggctgcggagttcctattgtggattcatattactcattgctgatgcccatcctcactttgact

agggcattggctgctgagtcccatatggatgctgatctcgcaaaaccacttattaagtgggatttgctgaaatatgattttacggaagagagactttgtctcttcgaccgttattt

taaatattgggaccagacataccatcccaattgtattaactgtttggatgataggtgtatccttcattgtgcaaactttaatgtgttattttctactgtgtttccacctacaagttttgg

accactagtaagaaaaatatttgtagatggtgttccttttgttgtttcaactggataccattttcgtgagttaggagtcgtacataatcaggatgtaaacttacatagctcgcgtctc

agtttcaaggaacttttagtgtatgctgctgatccagctatgcatgcagcttctggcaatttattgctagataaacgcactacatgatttcagtagctgcactaacaaacaatgtt

gcttttcaaactgtcaaacccggtaattttaataaagacttttatgactttgctgtgtctaaaggtttctttaaggaaggaagttctgttgaactaaaacacttcttctttgctcaggat

ggcaacgctgctatcagtgattatgactattatcgttataatctgccaacaatgtgtgatatcagacaactcctattcgtagttgaagttgttgataaatactttgattgttacgatg

gtggctgtattaatgccaaccaagtaatcgttaacaatctggataaatcagctggtttcccatttaataaatggggtaaggctagactttattatgactcaatgagttatgaggat

caagatgcacttttcgcgtatactaagcgtaatgtcatccctactataactcaaatgaatcttaagtatgccattagtgcaaagaatagagctcgcaccgtagaggtgtactat

ctgtagtactatgacaaatagacagtttcatcagaaattattgaagtcaatagccgccactagaggagctactgtggtaattggaacaagcaagttttacggtggctggcata

atatgttaaaaactgtttacagtgatgtagaaactccacaccttatgggttgggattatccaaaatgtgacagagccatgcctaacatgcttaggataatggcctctcttgttctt

gctcgcaaacataacacttgctgtaacttatcacaccgtttctacaggttagctaacgagtgtgcgcaagtattaagtgagatggtcatgtgtggcggctcactatatgttaaac

caggtggaacatcatccggtgatgctacaactgcttatgctaatagtgtctttaacatttgtcaagctgttacagccaatgtaaatgcacttattcaactgatggtaataagata

gctgacaagtatgtccgcaatctacaacacaggctctatgagtgtactatagaaatagggatgttgatcatgaattcgtggatgagttttacgcttacctgcgtaaacatttctc

catgatgattattctgatgatgccgttgtgtgctataacagtaactatgcggctcaaggtttagtagctagcattaagaactttaaggcagttattattatcaaaataatgtgttc

atgtctgaggcaaaatgttggactgagactgaccttactaaaggacctcacgaattttgctcacagcatacaatgctagttaaacaaggagatgattacgtgtacctgccttac

ccagatccatcaagaatattaggcgcaggctgttttgtcgatgatattgtcaaaacagatggtacacttatgattgaaaggttcgtgtcactggctattgatgcttacccacttac

aaaacatcctaatcaggagtatgctgatgtctttcacttgtatttacaatacattagaaagttacatgatgagcttactggccacatgttggacatgtattccgtaatgctaactaat

gataacacctcacggtactgggaacctgagttttatgaggctatgtacacaccacatacagtcttgcaggctgtaggtgcttgtgtattgtgcaattcacagacttcacttcgtt

gcggtgcctgtattaggagaccattcctatgttgcaagtgctgctatgaccatgtcatttcaacatcacacaaattagtgttgtctgttaatccctatgtttgcaatgccccaggtt

gtgatgtcactgatgtgacacaactgtatctaggaggtatgagctattattgcaagtcacataagcctcccattagttttccattatgtgctaatggtcaggtttttggtttatacaa

aaacacatgtgtaggcagtgacaatgtcactgacttcaatgcgatagcaacatgtgattggactaatgctggcgattacatacttgccaacacttgtactgagagactcaagc

ttttcgcagcagaaacgctcaaagccactgaggaaacatttaagctgtcatatggtattgccactgtacgcgaagtactctctgacagagaattgcatctttcatgggaggttg

gaaaacctagaccaccattgaacagaaactatgtattactggttaccgtgtaactaaaaatagtaaagtacagattggagagtacacctttgaaaaaggtgactatggtgat

gctgttgtgtacagaggtactacgacatacaagttgaatgttggtgattactttgtgttgacatctcacactgtaatgccacttagtgcacctactctagtgccacaagagcact

atgtgagaattactggcttgtacccaacactcaacatctcagatgagttttctagcaatgttgcaaattatcaaaaggtcggcatgcaaaagtactctacactccaaggaccac

ctggtactggtaagagtcattttgccatcggacttgactctattacccatctgctcgcatagtgtatacggcatgctctcatgcagctgttgatgccctatgtgaaaaggcatta

aaatatttgcccatagataaatgtagtagaatcatacctgcgcgtgcgcgcgtagagtgttttgataaattcaaagtgaattcaacactagaacagtatgttttagcactgtaaa

tgcattgccagaaacaactgctgacattgtagtctttgatgaaatctctatggctactaattatgacttgagtgttgtcaatgctagacttcgtgcaaaacactacgtctatattgg

cgatcctgctcaattaccagccccccgcacattgctgactaaaggcacactagaaccagaatattttaattcagtgtgcagacttatgaaaacaataggtccagacatgttcct

tggaacttgtcgccgttgtcctgctgaaattgttgacactgtgagtgattagtttatgacaataagctaaaagcacacaaggataagtcagctcaatgcttcaaaatgttctaca

aaggtgttattacacatgatgtttcatctgcaatcaacagacctcaaataggcgttgtaagagaatttcttacacgcaatcctgcttggagaaaagctgtttttatctcaccttata

attcacagaacgctgtagcttcaaaaatcttaggattgcctacgcagactgttgattcatcacagggttctgaatatgactatgtcatattcacacaaactactgaaacagcaca

ctcttgtaatgtcaaccgcttcaatgtggctatcacaagggcaaaaattggcattttgtgcataatgtctgatagagatctttatgacaaactgcaatttacaagtctagaaatac

cacgtcgcaatgtggctacattacaagcagaaaatgtaactggactttttaaggactgtagtaagatcattactggtcttcatcctacacaggcacctacacacctcagcgttg

atataaagttcaagactgaaggattatgtgttgacataccaggcataccaaaggacatgacctaccgtagactcatctctatgatgggtttcaaaatgaattaccaagtcaatg

gttaccctaatatgtttatcacccgcgaagaagctattcgtcacgttcgtgcgtggattggctttgatgtagagggctgtcatgcaactagagatgctgtgggtactaacctac

ctctccagctaggattttctacaggtgttaacttagtagctgtaccgactggttatgttgacactgaaaataacacagaattcaccagagttaatgcaaaacctccaccaggtg

accagtttaaacatcttataccactcatgtataaaggcttgccaggaatgtagtgcgtattaagatagtacaaatgctcagtgatacactgaaaggattgtcagacagagtcg

tgttcgtcctttgggcgcatggctttgagcttacatcaatgaagtactttgtcaagattggacctgaaagaacgtgttgtctgtgtgacaaacgtgcaacttgatttctacttcat

cagatacttatgcctgctggaatcattctgtgggttttgactatgtctataacccatttatgattgatgttcagcagtggggctttacgggtaaccttcagagtaaccatgaccaa

cattgccaggtacatggaaatgcacatgtggctagttgtgatgctatcatgactagatgtttagcagtccatgagtgctttgttaagcgcgttgattggtctgttgaataccctatt

ataggagatgaactgagggttaattctgcttgcagaaaagtacaacacatggttgtgaagtctgcattgcttgctgataagtttccagttcttcatgacattggaaatccaaagg

ctatcaagtgtgtgcctcaggctgaagtagaatggaagttctacgatgctcagccatgtagtgacaaagcttacaaaatagaggaactcttctattcttatgctacacatcacg

ataaattcactgatggtgtttgtttgttttggaattgtaacgttgatcgttacccagccaatgcaattgtgtgtaggtttgacacaagagtcttgtcaaacttgaacttaccaggctg

tgatggtggtagtttgtatgtgaataagcatgcattccacactccagctttcgataaaagtgcatttactaatttaaagcaattgcctttatttactattctgatagtccttgtgagtc

tcatggcaaacaagtagtgtcggatattgattatgttccactcaaatctgctacgtgtattacacgatgcaatttaggtggtgctgtttgcagacaccatgcaaatgagtaccga

cagtacttggatgcatataatatgatgatttctgctggatttagcctatggatttacaaacaatttgatacttataacctgtggaatacatttaccaggttacagagtttagaaaatg

tggcttataatgttgttaataaaggacactttgatggacacgccggcgaagcacctgtttccatcattaataatgctgtttacacaaaggtagatggtattgatgtggagatcttt

gaaaataagacaacacttcctgttaatgttgcatttgagctttgggctaagcgtaacattaaaccagtgccagagattaagatactcaataatttgggtgttgatatcgctgctaa

tactgtaatctgggactacaaaagagaagccccagcacatgtatctacaataggtgtctgcacaatgactgacattgccaagaaacctactgagagtgcttgttcttcacttac

tgtcttgtttgatggtagagtggaaggacaggtagacctttttagaaacgcccgtaatggtgttttaataacagaaggttcagtcaaaggtctaacaccttcaaagggaccag

cacaagctagcgtcaatggagtcacattaattggagaatcagtaaaaacacagtttaactactttaagaaagtagacggcattattcaacagttgcctgaaacctactttactc

agagcagagacttagaggattttaagcccagatcacaaatggaaactgactttctcgagctcgctatggatgaattcatacagcgatataagctcgagggctatgccttcga

acacatcgtttatggagatttcagtcatggacaacttggcggtcttcatttaatgataggcttagccaagcgctcacaagattcaccacttaaattagaggattttatccctatgg

acagcacagtgaaaaattacttcataacagatgcgcaaacaggttcatcaaaatgtgtgtgttctgtgattgatcttttacttgatgactttgtcgagataataaagtcacaagatt

tgtcagtgatttcaaaagtggtcaaggttacaattgactatgctgaaatttcattcatgattggtgtaaggatggacatgttgaaaccttctacccaaaactacaagcaagtcaa

gcgtggcaaccaggtgttgcgatgcctaacttgtacaagatgcaaagaatgcttcttgaaaagtgtgaccttcagaattatggtgaaaatgctgttataccaaaaggaataat

gatgaatgtcgcaaagtatactcaactgtgtcaatacttaaatacacttactttagctgtaccctacaacatgagagttattcactttggtgctggctctgataaaggagttgcac

caggtacagagtgctcagacaatggttgccaactggcacactacttgtcgattcagatcttaatgacttcgtctccgacgcagattctactttaattggagactgtgcaacagt

acatacggctaataaatgggaccttattattagcgatatgtatgaccctaggaccaaacatgtgacaaaagagaatgactctaaagaagggtttttcacttatctgtgtggattt

ataaagcaaaaactagccagggtggttctatagctgtaaagataacagagcattcttggaatgctgacctttacaagcttatgggccatttctcatggtggacagcttttgtta

caaatgtaaatgcatcatcatcggaagcatttttaattggggctaactatcttggcaagccgaaggaacaaattgatggctataccatgcatgctaactacattttctggagga

acacaaatcctatccagttgtcttcctattcactctttgacatgagcaaatttcctcttaaattaagaggaactgctgtaatgtctcttaaggagaatcaaatcaatgatatgatttat

tctcttctggaaaaaggtaggcttatcattagagaaaacaacagagttgtggtttcaagtgatattcttgttaacaactaaacgaacatgtttattttcttattatttcttactctcact

agtggtagtgaccttgaccggtgcaccacttttgatgatgttcaagctcctaattacactcaacatacttcatctatgaggggggtttactatcctgatgaaatttttagatcagac

actctttatttaactcaggatttatttcttccattttattctaatgttacagggtttcatactattaatcatacgtttggcaaccctgtcataccttttaaggatggtatttattttgctgcca

cagagaaatcaaatgttgtccgtggttgggtttttggttctaccatgaacaacaagtcacagtcggtgattattattaacaattctactaatgttgttatacgagcatgtaactttga

attgtgtgacaaccctttctttgctgtttctaaacccatgggtacacagacacatactatgatattcgataatgcatttaattgcactttcgagtacatatctgatgccttttcgcttga

tgtttcagaaaagtcaggtaattttaaacacttacgagagtttgtgtttaaaaataaagatgggtttctctatgtttataagggctatcaacctatagatgtagttcgtgatctacctt

ctggttttaacactttgaaacctatttttaagttgcctcttggtattaacattacaaattttagagccattcttacagccttttcacctgctcaagacatttggggcacgtcagctgca

gcctatt-ttgttggctatttaaagccaactacatttatgctcaagtatgatgaaaatggtacaatcacagatgctgttgattgttctcaaaatccacttgctgaactcaaatgctctg

ttaagagctttgagattgacaaaggaatttaccagacctctaatttcagggttgttccctcaggagatgttgtgagattccctaatattacaaacttgtgtccttttggagaggtttt

taatgctactaaattcccttctgtctatgcatgggagagaaaaaaaatttctaattgtgttgctgattactctgtgctctacaactcaacatttttttcaacctttaagtgctatggcgt

ttctgccactaagttgaatgatctttgcttctccaatgtctatgcagattcttttgtagtcaagggagatgatgtaagacaaatagcgccaggacaaactggtgttattgctgatta

taattataaattgccagatgatttcatgggttgtgtccttgcttggaatactaggaacattgatgctacttcaactggtaattataattataaatataggtatcttagacatggcaag

cttaggccattgagagagacatatctaatgtgcctttctcccctgatggcaaaccttgcaccccacctgctcttaattgttattggccattaaatgattatggtttttacaccacta

ctggcattggctaccaaccttacagagttgtagtactttatttgaacttttaaatgcaccggccacggtttgtggaccaaaattatccactgaccttattaagaaccagtgtgtca

attttaattttaatggactcactggtactggtgtgttaactccttcttcaaagagatttcaaccatttcaacaatttggccgtgatgtttctgatttcactgattccgttcgagatccta

aaacatctgaaatattagacatttcaccttgcgcttttgggggtgtaagtgtaattacacctggaacaaatgcttcatctgaagttgctgttctatatcaagatgttaactgcactg

atgtttctacagcaattcatgcagatcaactcacaccagcttggcgcatatattctactggaaacaatgtattccagactcaagcaggctgtcttataggagctgagcatgtcg

acacttcttatgagtgcgacattcctattggagaggcatttgtgctagttaccatacagtttattattacgtagtactagccaaaaatctattgtggcttatactatgtattaggtg

ctgatagttcaattgcttactctaataacaccattgctatacctactaacttttcaattagcattactacagaagtaatgcctgtttctatggctaaaacctccgtagattgtaatatgt

acatctgcggagattctactgaatgtgctaatttgcttctccaatatggtagcttttgcacacaactaaatcgtgcactctcaggtattgctgctgaacaggatcgcaacacacg

tgaagtgttcgctcaagtcaaacaaatgtacaaaaccccaactttgaaatattttggtggttttaatttttcacaaatattacctgaccctctaaagccaactaagaggtcttttatt

gaggacttgctctttaataaggtgacactcgctgatgctggcttcatgaagcaatatggcgaatgcctaggtgatattaatgctagagatctcatttgtgcgcagaagttcaat

ggacttacagtgttgccacctctgctcactgatgatatgattgctgcctacactgctgctctagttagtggtactgccactgctggatggacatttggtgctggcgctgctcttc

aaataccttttgctatgcaaatggcatataggttcaatggcattggagttacccaaaatgttctctatgagaaccaaaaacaaatcgccaaccaatttaacaaggcgattagtc

aaattcaagaatcacttacaacaacatcaactgcattgggcaagctgcaagacgttgttaaccagaatgctcaagcattaaacacacttgttaaacaacttagctctaattttgg

tgcaatttcaagtgtgctaaatgatatcctttcgcgacttgataaagtcgaggcggaggtacaaattgacaggttaattacaggcagacttcaaagccttcaaacctatgtaac

acaacaactaatcagggctgctgaaatcagggcttctgctaatcttgctgctactaaaatgtctgagtgtgttcttggacaatcaaaaagagttgacttttgtggaaagggcta

ccaccttatgtccttcccacaagcagccccgcatggtgttgtcttcctacatgtcacgtatgtgccatcccaggagaggaacttcaccacagcgccagcaatttgtcatgaag

gcaaagcatacttccctcgtgaaggtgtttttgtgtttaatggcacttcttggtttattacacagaggaacttatttctccacaaataattactacagacaatacatttgtctcagga

aattgtgatgtcgttattggcatcattaacaacacagtttatgatcctctgcaacctgagcttgactcattcaaagaagagctggacaagtacttcaaaaatcatacatcaccag

atgttgatcttggcgacatttcaggcattaacgcttctgtcgtcaacattcaaaaagaaattgaccgcctcaatgaggtcgctaaaaatttaaatgaatcactcattgaccttcaa

gaattgggaaaatatgagcaatatattaaatggccttggtatgtttggctcggcttcattgctggactaattgccatcgtcatggttacaatcttgattgttgcatgactagttgtt

gcagttgcctcaagggtgcatgctcttgtggttcttgctgcaagtttgatgaggatgactctgagccagttctcaagggtgtcaaattacattacacataaacgaacttatggat

ttgtttatgagattttttactcttagatcaattactgcacagccagtaaaaattgacaatgcttctcctgcaagtactgttcatgctacagcaacgataccgctacaagcctcactc

cattcggatggcttgttattggcgttgcatttcttgctgtttttcagagcgctaccaaaataattgcgctcaataaaagatggcagctagccattataagggcttccagttcattt

gcaatttactgctgctatttgttaccatctattcacatatttgcttgtcgctgcaggtatggaggcgcaatttttgtacctctatgccttgatatattttctacaatgcatcaacgcat

gtagaattattatgagatgttggctttgttggaagtgcaaatccaagaacccattactttatgatgccaactactttgtttgctggcacacacataactatgactactgtataccat

ataacagtgtcacagatacaattgtcgttactgaaggtgacggcatttcaacaccaaaactcaaagaagactaccaaattggtggttattctgaggataggcactcaggtgtt

aaagactatgtcgttgtacatggctatttcaccgaagtttactaccagcttgagtctacacaaattactacagacactggtattgaaaatgctacattcttcatctttaacaagctt

gttaaagacccaccgaatgtgcaaatacacacaatcgacggctcttcaggagttgctaatccagcaatggatccaatttatgatgagccgacgacgactactagcgtgcctt

tgtaagcacaagaaagtgagtacgaacttatgtactcattcgtttcggaagaaacaggtacgttaatagttaatagcgtacttctttttcttgattcgtggtattcttgctagtcac

actagccatccttactgcgcttcgattgtgtgcgtactgctgcaatattgttaacgtgagtttagtaaaaccaacggtttacgtctactcgcgtgttaaaaatctgaactcttctga

aggagttcctgatcttctggtctaaacgaactaactattattattattctgtttggaactttaacattgcttatcatggcagacaacggtactattaccgttgaggagcttaaacaac

tcctggaacaatggaacctagtaataggtttcctattcctagcctggattatgttactacaatttgcctattctaatcggaacaggtttttgtacataataaagcttgttttcctctgg

ctcttgtggccagtaacacttgcttgttttgtgcttgctgctgtctacagaattaattgggtgactggcgggattgcgattgcaatggcttgtattgtaggcttgatgtggcttagc

tacttcgttgcttccttcaggctgtttgctcgtacccgctcaatgtggtcattcaacccagaaacaaacattcttctcaatgtgcctctccgggggacaattgtgaccagaccgc

tcatggaaagtgaacttgtcattggtgctgtgatcattcgtggtcacttgcgaatggccggacactccctagggcgctgtgacattaaggacctgccaaaagagatcactgt

ggctacatcacgaacgattcttattacaaattaggagcgtcgcagcgtgtaggcactgattcaggttttgctgcatacaaccgctaccgtattggaaactataaattaaataca

gaccacgccggtagcaacgacaatattgattgctagtacagtaagtgacaacagatgtttcatcttgttgacttccaggttacaatagcagagatattgattatcattatgagg

actttcaggattgctatttggaatcttgacgttataataagttcaatagtgagacaattatttaagcctctaactaagaagaattattcggagttagatgatgaagaacctatggag

ttagattatccataaaacgaacatgaaaattattctcttcctgacattgattgtatttacatcttgcgagctatatcactatcaggagtgtgttagaggtacgactgtactactaaaa

gaaccttgcccatcaggaacatacgagggcaattcaccatttcaccctcttgctgacaataaatttgcactaacttgcactagcacacactttgatttgcttgtgctgacggta

ctcgacatacctatcagctgcgtgcaagatcagtttcaccaaaacttttcatcagacaagaggaggttcaacaagagctctactcgccactttttctcattgttgctgctctagta

tttttaatactttgcttcaccattaagagaaagacagaatgaatgagctcactttaattgacttctatttgtgctttttagcctttctgctattccttgttttaataatgcttattatattttg

gttttcactcgaaatccaggatctagaagaaccttgtaccaaagtctaaacgaacatgaaacttctcattgttttgacttgtatttactatgcagttgcatatgcactgtagtacagc

gctgtgcatctaataaacctcatgtgcttgaagatccttgtaaggtacaacactaggggtaatacttatagcactgcttggctttgtgctctaggaaaggttttaccttttcataga

tggcacactatggttcaaacatgcacacctaatgttactatcaactgtcaagatccagaggtggtgcgcttatagctaggtgttggtaccttcatgaaggtcaccaaactgct

gcatttagagacgtacttgttgttttaaataaacgaacaaattaaaatgtctgataatggaccccaatcaaaccaacgtagtgccccccgcattacatttggtggacccacaga

ttcaactgacaataaccagaatggaggacgcaatggggcaaggccaaaacagcgccgaccccaaggtttacccaataatactgcgtcttggttcacagctctcactcagc

atggcaaggaggaacttagattccctcgaggccagggcgttccaatcaacaccaatagtggtccagatgaccaaattggctactaccgaagagctacccgacgagttcgt

ggtggtgacggcaaaatgaaagagctcagccccagatggtacttctattacctaggaactggcccagaagcttcacttccctacggcgctaacaaagaaggcatcgtatg

ggttgcaactgagggagccttgaatacacccaaagaccacattggcacccgcaatcctaataacaatgctgccaccgtgctacaacttcctcaaggaacaacattgccaa

aaggatctacgcagagggaagcagaggcggcagtcaagcctcttctcgctcctcatcacgtagtcgcggtaattcaagaaattcaactcctggcagcagtaggggaaat

tctcctgctcgaatggctagcggaggtggtgaaactgccctcgcgctattgctgctagacagattgaaccagcttgagagcaaagtttctggtaaaggccaacaacaacaa

ggccaaactgtcactaagaaatctgctgctgaggcatctaaaaagcctcgccaaaaacgtactgccacaaaacagtacaacgtcactcaagcatttgggagacgtggtcc

agaacaaacccaaggaaatttcggggaccaagacctaatcagacaaggaactgattacaaacattggccgcaaattgcacaatttgctccaagtgcctctgcattctttgga

atgtcacgcattggcatggaagtcacaccttcgggaacatggctgacttatcatggagccattaaattggatgacaaagatccacaattcaaagacaacgtcatactgctga

acaagcacattgacgcatacaaaacattcccaccaacagagcctaaaaaggacaaaaagaaaaagactgatgaagctcagcctttgccgcagagacaaaagaagcag

cccactgtgactatatcctgcggctgacatggatgatttctccagacaacttcaaaattccatgagtggagcttctgctgattcaactcaggcataaacactcatgatgacca

cacaaggcagatgggctatgtaaacgttttcgcaattccgtttacgatacatagtctactcttgtgcagaatgaattctcgtaactaaacagcacaagtaggtttagttaacttta

atctcacatagcaatctttaatcaatgtgtaacattagggaggacttgaaagagccaccacattttcatcgaggccacgcggagtacgatcgagggtacagtgaataatgct

agggagagctgcctatatggaagagccctaatgtgtaaaattaattttagtagtgctatccccatgtgattttaatagcttcttaggagaatgacaaaaaaaaaaaaaaaaaaa

aaaaa

2409
MERS-CoV
gatttaagtgaatagcttggctatctcacttcccctcgttctcttgcagaactttgattttaacgaacttaaataaaagccctgttgtttagcgtatcgttgcacttgtctggtgggat

genome
tgtggcattaatttgcctgctcatctaggcagtggacatatgctcaacactgggtataattctaattgaatactatttttcagttagagcgtcgtgtctcttgtacgtctcggtcaca

(Genbank
atacacggtttcgtccggtgcgtggcaattcggggcacatcatgtctttcgtggctggtgtgaccgcgcaaggtgcgcgcggtacgtatcgagcagcgctcaactctgaaa

Accession
aacatcaagaccatgtgtctctaactgtgccactctgtggttcaggaaacctggttgaaaaactttcaccatggttcatggatggcgaaaatgcctatgaagtggtgaaggcc

No.
atgttacttaaaaaggagccacttctctatgtgcccatccggctggctggacacactagacacctcccaggtcctcgtgtgtacctggttgagaggctcattgcttgtgaaaat

NC_
ccattcatggttaaccaattggcttatagctctagtgcaaatggcagcctggttggcacaactttgcagggcaagcctattggtatgttcttcccttatgacatcgaacttgtcac

019843.3)
aggaaagcaaaatattctcctgcgcaagtatggccgtggtggttatcactacaccccattccactatgagcgagacaacacctcttgccctgagtggatggacgattttgag

gcggatcctaaaggcaaatatgcccagaatctgcttaagaagttgattggcggtgatgtcactccagttgaccaatacatgtgtggcgttgatggaaaacccattagtgccta

cgcatttttaatggccaaggatggaataaccaaactggctgatgttgaagcggacgtcgcagcacgtgctgatgacgaaggcttcatcacattaaagaacaatctatataga

ttggtttggcatgttgagcgtaaagacgttccatatcctaagcaatctatttttactattaatagtgtggtccaaaaggatggtgttgaaaacactcctcctcactattttactcttgg

atgcaaaattttaacgctcaccccacgcaacaagtggagtggcgtttctgacttgtccctcaaacaaaaactcctttacaccttctatggtaaggagtcacttgagaacccaac

ctacatttaccactccgcattcattgagtgtggaagttgtggtaatgattcctggcttacagggaatgctatccaagggtttgcctgtggatgtggggcatcatatacagctaat

gatgtcgaagtccaatcatctggcatgattaagccaaatgctcttctttgtgctacttgcccctttgctaagggtgatagctgttcttctaattgcaaacattcagttgctcagttgg

ttagttacctttctgaacgctgtaatgttattgctgattctaagtccttcacacttatattggtggcgtagcttacgcctactttggatgtgaggaaggtactatgtactttgtgccta

gagctaagtctgttgtctcaaggattggagactccatctttacaggctgtactggctcttggaacaaggtcactcaaattgctaacatgttcttggaacagactcagcattccct

taactttgtgggagagttcgttgtcaacgatgttgtcctcgcaattctctctggaaccacaactaatgttgacaaaatacgccagcttctcaaaggtgtcacccttgacaagttg

cgtgattatttagctgactatgacgtagcagtcactgccggcccattcatggataatgctattaatgttggtggtacaggattacagtatgccgccattactgcaccttatgtagt

tctcactggcttaggtgagtcctttaagaaagttgcaaccataccgtataaggtttgcaactctgttaaggatactctggcttattatgctcacagcgtgttgtacagagtttttcct

tatgacatggattctggtgtgtcatcctttagtgaactactttttgattgcgttgatattcagtagcttctacctattttttagtccgcatcttgcaagataagactggcgactttatgt

ctacaattattacttcctgccaaactgctgttagtaagcttctagatacatgttttgaagctacagaagcaacatttaacttcttgttagatttggcaggattgttcagaatctttctcc

gcaatgcctatgtgtacacttcacaagggtttgtggtggtcaatggcaaagtttctacacttgtcaaacaagtgttagacttgcttaataagggtatgcaacttttgcatacaaag

gtctcctgggctggttctaaaatcattgctgttatctacagcggcagggagtctctaatattcccatcgggaacctattactgtgtcaccactaaggctaagtccgttcaacaag

atcttgacgttatt-ttgcctggtgagttttccaagaagcagttaggactgctccaacctactgacaattctacaactgttagtgttactgtatccagtaacatggttgaaactgttgt

gggtcaacttgagcaaactaatatgcatagtcctgatgttatagtaggtgactatgtcattattagtgaaaaattgtttgtgcgtagtaaggaagaagacggatttgccttctacc

ctgcttgcactaatggtcatgctgtaccgactctctttagacttaagggaggtgcacctgtaaaaaaagtagcctttggcggtgatcaagtacatgaggttgctgctgtaagaa

gtgttactgtcgagtacaacattcatgctgtattagacacactacttgcttcttctagtcttagaacctttgttgtagataagtctttgtcaattgaggagtttgctgacgtagtaaag

gaacaagtctcagacttgcttgttaaattactgcgtggaatgccgattccagattttgatttagacgattttattgacgcaccatgctattgctttaacgctgagggtgatgcatcc

tggtcttctactatgatcttctctcttcaccccgtcgagtgtgacgaggagtgttctgaagtagaggcttcagatttagaagaaggtgaatcagagtgcatttctgagacttcaa

ctgaacaagttgacgtttctcatgagacttctgacgacgagtgggctgctgcagttgatgaagcgttccctctcgatgaagcagaagatgttactgaatctgtgcaagaaga

agcacaaccagtagaagtacctgttgaagatattgcgcaggttgtcatagctgacaccttacaggaaactcctgttgtgcctgatactgttgaagtcccaccgcaagtggtg

aaacttccgtctgcacctcagactatccagcccgaggtaaaagaagttgcacctgtctatgaggctgataccgaacagacacagaatgttactgttaaacctaagaggttac

gcaaaaagcgtaatgttgaccattgtccaattttgaacataaggttattacagagtgcgttaccatagttttaggtgacgcaattcaagtagccaagtgctatggggagtctgt

gttagttaatgctgctaacacacatcttaagcatggcggtggtatcgctggtgctattaatgcggcttcaaaaggggctgtccaaaaagagtcagatgagtatattctggctaa

agggccgttacaagtaggagattcagttctcttgcaaggccattctctagctaagaatatcctgcatgtcgtaggcccagatgcccgcgctaaacaggatgtttctctccttag

taagtgctataaggctatgaatgcatatcctcttgtagtcactcctcttgtttcagcaggcatatttggtgtaaaaccagctgtgtcttttgattatcttattagggaggctaagact

agagttttagtcgtcgttaattcccaagatgtctataagagtcttaccatagttgacattccacagagtttgactttttcatatgatgggttacgtggcgcaatacgtaaagctaaa

gattatggttttactgtttttgtgtgcacagacaactctgctaacactaaagttcttaggaacaagggtgttgattatactaagaagtttcttacagttgacggtgtgcaatattattg

ctacacgtctaaggacactttagatgatatcttacaacaggctaataagtagttggtattatatctatgcctttgggatatgtgtctcatggtttagacttaatgcaagcagggag

tgtcgtgcgtagagttaacgtgccctacgtgtgtctcctagctaataaagagcaagaagctattttgatgtctgaagacgttaagttaaacccttcagaagattttataaagcac

gtccgcactaatggtggttacaattcttggcatttagtcgagggtgaactattggtgcaagacttacgcttaaataagctcctgcattggtctgatcaaaccatatgctacaagg

atagtgtgttttatgttgtaaagaatagtacagcttttccatttgaaacactttcagcatgtcgtgcgtatttggattcacgcacgacacagcagttaacaatcgaagtcttagtga

ctgtcgatggtgtaaattttagaacagtcgttctaaataataagaacacttatagatcacagcttggatgcgttttattaatggtgctgatatttctgacaccattcctgatgagaa

acagaatggtcacagtttatatctagcagacaatttgactgctgatgaaacaaaggcgcttaaagagttatatggccccgttgatcctactttcttacacagattctattcactta

aggctgcagtccatgggtggaagatggttgtgtgtgataaggtacgttctctcaaattgagtgataataattgttatcttaatgcagttattatgacacttgatttattgaaggaca

ttaaatttgttatacctgactacagcatgcatttatgaaacataagggcggtgattcaactgacttcatagccctcattatggcttatggcaattgcacatttggtgaccagatg

atgcctctcggttacttcataccgtgcttgcaaaggctgagttatgctgttctgcacgcatggtttggagagagtggtgcaatgtctgtggcataaaagatgttgttctacaagg

cttaaaagcttgttgttacgtgggtgtgcaaactgttgaagatctgcgtgctcgcatgacatatgtatgccagtgtggtggtgaacgtcatcggcaattagtcgaacacacca

ccccctggttgctgctctcaggcacaccaaatgaaaaattggtgacaacctccacggcgcctgattttgtagcatttaatgtctttcagggcattgaaacggctgttggccatt

atgttcatgctcgcctgaagggtggtcttattttaaagtttgactaggcaccgttagcaagacttcagactggaagtgcaaggtgacagatgtacttttccccggccaaaaat

acagtagcgattgtaatgtcgtacggtattctttggacggtaatttcagaacagaggttgatcccgacctatctgctttctatgttaaggatggtaaatactttacaagtgaacca

cccgtaacatattcaccagctacaattttagctggtagtgtctacactaatagctgccttgtatcgtctgatggacaacctggcggtgatgctattagtttgagttttaataaccttt

tagggtttgattctagtaaaccagtcactaagaaatacacttactccttcttgcctaaagaagacggcgatgtgttgttggctgagtttgacacttatgaccctatttataagaatg

gtgccatgtataaaggcaaaccaattctttgggtcaataaagcatcttatgatactaatcttaataagttcaatagagctagtttgcgtcaaatttttgacgtagcccccattgaac

tcgaaaataaattcacacctttgagtgtggagtctacaccagttgaacctccaactgtagatgtggtagcacttcaacaggaaatgacaattgtcaaatgtaagggtttaaata

aacctttcgtgaaggacaatgtcagtttcgttgctgatgattcaggtactcccgttgttgagtatctgtctaaagaagacctacatacattgtatgtagaccctaagtatcaagtc

attgtcttaaaagacaatgtactttcttctatgcttagattgcacaccgttgagtcaggtgatattaacgttgttgcagcttccggatctttgacacgtaaagtgaagttactattta

gggcttcattttatttcaaagaatttgctacccgcactttcactgctaccactgctgtaggtagttgtataaagagtgtagtgcggcatctaggtgttactaaaggcatattgaca

ggctgttttagttttgccaagatgttatttatgcttccactagcttactttagtgattcaaaactcggcaccacagaggttaaagtgagtgattgaaaacagccggcgttgtgac

aggtaatgttgtaaaacagtgttgcactgctgctgttgatttaagtatggataagttgcgccgtgtggattggaaatcaaccctacggttgttacttatgttatgcacaactatggt

attgttgtcttctgtgtatcacttgtatgtcttcaatcaggtcttatcaagtgatgttatgtttgaagatgcccaaggtttgaaaaagttctacaaagaagttagagcttacctagga

atctcttctgcttgtgacggtcttgcttcagcttatagggcgaattcctttgatgtacctacattctgcgcaaaccgttctgcaatgtgtaattggtgcttgattagccaagattcca

taactcactacccagctcttaagatggttcaaacacatcttagccactatgttcttaacatagattggttgtggtttgcatttgagactggtttggcatacatgctctatacctcggc

cttcaactggttgttgttggcaggtacattgcattatttctttgcacagacttccatatttgtagactggcggtcatacaattatgctgtgtctagtgccttctggttattcacccacat

tccaatggcgggtttggtacgaatgtataatttgttagcatgcctttggcttttacgcaagttttatcagcatgtaatcaatggttgcaaagatacggcatgcttgctctgctataa

gaggaaccgacttactagagttgaagcttctaccgttgtagtggtggaaaacgtacgttttatatcacagcaaatggcggtatttcattctgtcgtaggcataattggaattgt

gtggattgtgacactgcaggtgtggggaataccttcatctgtgaagaagtcgcaaatgacctcactaccgccctacgcaggcctattaacgctacggatagatcacattatta

tgtggattccgttacagttaaagagactgttgttcagtttaattatcgtagagacggtcaaccattctacgagcggtttcccctctgcgcttttacaaatctagataagttgaagtt

caaagaggtagtaaaactactactggtatacctgaatacaactttatcatctacgactcatcagatcgtggccaggaaagtttagctaggtctgcatgtgtttattattctcaagt

cttgtgtaaatcaattcttttggttgactcaagtttggttacttctgttggtgattctagtgaaatcgccactaaaatgtttgattcctttgttaatagtttcgtctcgctgtataatgtca

cacgcgataagttggaaaaacttatctctactgctcgtgatggcgtaaggcgaggcgataacttccatagtgtcttaacaacattcattgacgcagcacgaggccccgcag

gtgtggagtctgatgttgagaccaatgaaattgttgactctgtgcagtatgctcataaacatgacatacaaattactaatgagagctacaataattatgtaccctcatatgttaaa

cctgatagtgtgtctaccagcgatttaggtagtctcattgattgtaatgcggcttcagttaaccaaattgtcttgcgtaattctaatggtgcttgcatttggaacgctgctgcatata

tgaaactctcggatgcacttaaacgacagattcgcattgcatgccgtaagtgtaatttagctttccggttaaccacctcaaagctacgcgctaatgataatatcttatcagttaga

ttcactgctaacaaaattgttggtggtgctcctacatggtttaatgcgttgcgtgactttacgttaaagggttatgttcttgctaccattattgtgtttctgtgtgctgtactgatgtatt

tgtgtttacctacattttctatggcacctgttgaattttatgaagaccgcatcttggactttaaagttcttgataatggtatcattagggatgtaaatcctgatgataagtgattgcta

ataagcaccggtccttcacacaatggtatcatgagcatgttggtggtgtctatgacaactctatcacatgcccattgacagttgcagtaattgctggagttgctggtgctcgcat

tccagacgtacctactacattggcttgggtgaacaatcagataattttattgtttctcgagtctttgctaatacaggcagtgtttgctacactcctatagatgagataccctataag

agtttctctgatagtggttgcattcttccatctgagtgcactatgtttagggatgcagagggccgtatgacaccatactgccatgatcctactgttttgcctggggcttttgcgtac

agtcagatgaggcctcatgttcgttacgacttgtatgatggtaacatgtttattaaatttcctgaagtagtatttgaaagtacacttaggattactagaactctgtcaactcagtact

gccggttcggtagttgtgagtatgcacaagagggtgtttgtattaccacaaatggctcgtgggccatttttaatgaccaccatcttaatagacctggtgtctattgtggctctgat

tttattgacattgtcaggcggttagcagtatcactgttccagcctattacttatttccaattgactacctcattggtcttgggtataggtttgtgtgcgttcctgactttgctcttctatt

atattaataaagtaaaacgtgatttgcagattacacccagtgtgctgtaattgctgttgttgctgctgttcttaatagcttgtgcatctgctttgttacctctataccattgtgtatagt

accttacactgcattgtactattatgctacattctattttactaatgagcctgcatttattatgcatgtttcttggtacattatgttcgggcctatcgttcccatatggatgacctgcgtc

tatacagttgcaatgtgattagacacttcttctgggttttagcttattttagtaagaaacatgtagaagtttttactgatggtaagcttaattgtagtttccaggacgctgcctctaat

atctttgttattaacaaggacacttatgcagctcttagaaactctttaactaatgatgcctattcacgatttttggggttgtttaacaagtataagtacttctctggtgctatggaaac

agccgcttatcgtgaagctgcagcatgtcatcttgctaaagccttacaaacatacagcgagactggtagtgatcttctttaccaaccacccaactgtagcataacctaggcgt

gttgcaaagcggtttggtgaaaatgtcacatcccagtggagatgttgaggcttgtatggttcaggttacctgcggtagcatgactcttaatggtctttggcttgacaacacagt

ctggtgcccacgacacgtaatgtgcccggctgaccagttgtctgatcctaattatgatgccttgttgatttctatgactaatcatagtttcagtgtgcaaaaacacattggcgctc

cagcaaacttgcgtgttgttggtcatgccatgcaaggcactcttttgaagttgactgtcgatgttgctaaccctagcactccagcctacacttttacaacagtgaaacctggcg

cagcatttagtgtgttagcatgctataatggtcgtccgactggtacattcactgttgtaatgcgccctaactacacaattaagggttcctttctgtgtggttcttgtggtagtgttgg

ttacaccaaggagggtagtgtgatcaatttctgttacatgcatcaaatggaacttgctaatggtacacataccggttcagcatttgatggtactatgtatggtgcctttatggata

aacaagtgcaccaagttcagttaacagacaaatactgcagtgttaatgtagtagcttggctttacgcagcaatacttaatggttgcgcttggtttgtaaaacctaatcgcactag

tgttgtttcttttaatgaatgggctcttgccaaccaattcactgaatttgttggcactcaatccgttgacatgttagctgtcaaaacaggcgttgctattgaacagctgattatgcg

atccaacaactgtatactgggttccagggaaagcaaatccttggcagtaccatgttggaagatgaattcacacctgaggatgttaatatgcagattatgggtgtggttatgca

gagtggtgtgagaaaagttacatatggtactgcgcattggttgtttgcgacccttgtctcaacctatgtgataatcttacaagccactaaatttactttgtggaactacttgtttga

gactattcccacacagttgttcccactcttatttgtgactatggccttcgttatgttgttggttaaacacaaacacacctttttgacacttttcttgttgcctgtggctatttgtttgactt

atgcaaacatagtctacgagcccactactcccatttcgtcagcgctgattgcagttgcaaattggcttgcccccactaatgcttatatgcgcactacacatactgatattggtgt

ctacattagtatgtcacttgtattagtcattgtagtgaagagattgtacaacccatcactttctaactttgcgttagcattgtgcagtggtgtaatgtggttgtacacttatagcattg

gagaagcctcaagccccattgcctatctggtttttgtcactacactcactagtgattatacgattacagtctttgttactgtcaaccttgcaaaagtttgcacttatgccatctttgct

tactcaccacagcttacacttgtgtttccggaagtgaagatgatacttttattatacacatgtttaggtttcatgtgtacttgctattttggtgtcttctctcttttgaaccttaagcttag

agcacctatgggtgtctatgactttaaggtctcaacacaagagttcagattcatgactgctaacaatctaactgcacctagaaattcttgggaggctatggctctgaactttaag

ttaataggtattggcggtacaccttgtataaaggttgctgctatgcagtctaaacttacagatcttaaatgcacatctgtggttctcctctctgtgctccaacagttacacttagag

gctaatagtagggcctgggctttctgtgttaaatgccataatgatatattggcagcaacagaccccagtgaggctttcgagaaattcgtaagtctctttgctactttaatgactttt

tctggtaatgtagatcttgatgcgttagctagtgatatttttgacactcctagcgtacttcaagctactctttctgagttttcacacttagctacctttgctgagttggaagctgcgca

gaaagcctatcaggaagctatggactaggtgacacctcaccacaagttcttaaggctttgcagaaggctgttaatatagctaaaaacgcctatgagaaggataaggcagt

ggcccgtaagttagaacgtatggctgatcaggctatgacttctatgtataagcaagcacgtgctgaagacaagaaagcaaaaattgtcagtgctatgcaaactatgttgtttg

gtatgattaagaagctcgacaacgatgttcttaatggtatcatttctaacgctaggaatggttgtatacctcttagtgtcatcccactgtgtgcttcaaataaacttcgcgttgtaat

tcctgacttcaccgtaggaatcaggtagtcacatatccctcgcttaactacgctggggctttgtgggacattacagttataaacaatgtggacaatgaaattgttaagtcttca

gatgttgtagacagcaatgaaaatttaacatggccacttgttttagaatgcactagggcatccacttctgccgttaagttgcaaaataatgagatcaaaccttcaggtctaaaaa

ccatggttgtgtctgcgggtcaagagcaaactaactgtaatactagttccttagcttattacgaacctgtgcagggtcgtaaaatgctgatggctcttctttctgataatgcctat

ctcaaatgggcgcgtgttgaaggtaaggacggatttgtcagtgtagagctacaacctccttgcaaattcttgattgcgggaccaaaaggacctgaaatccgatatctctatttt

gttaaaaatcttaacaaccttcatcgcgggcaagtgttagggcacattgctgcgactgttagattgcaagctggttctaacaccgagtttgcctctaattcctcggtgttgtcact

tgttaacttcaccgttgatcctcaaaaagcttatctcgatttcgtcaatgcgggaggtgccccattgacaaattgtgttaagatgcttactcctaaaactggtacaggtatagcta

tatctgttaaaccagagagtacagctgatcaagagacttatggtggagcttcagtgtgtactattgccgtgcgcatatagaacatcctgatgtactggtgtttgtaaatataag

ggtaagtttgtccaaatccctgctcagtgtgtccgtgaccctgtgggattttgtttgtcaaataccccctgtaatgtctgtcaatattggattggatatgggtgcaattgtgactcg

cttaggcaagcagcactgccccaatctaaagattccaattttttaaacgagtccggggttctattgtaaatgcccgaatagaaccctgttcaagtggtttgtccactgatgtcgt

ctttagggcatttgacatctgcaactataaggctaaggttgctggtattggaaaatactacaagactaatacttgtaggtttgtagaattagatgaccaagggcatcatttagact

cctattttgtcgttaagaggcatactatggagaattatgaactagagaagcactgttacgacttgttacgtgactgtgatgctgtagctccccatgatttcttcatctttgatgtag

acaaagttaaaacacctcatattgtacgtcagcgtttaactgagtacactatgatggatcttgtatatgccctgaggcactttgatcaaaatagcgaagtgcttaaggctatctta

gtgaagtatggttgctgtgatgttacctactttgaaaataaactctggtttgattttgttgaaaatcccagtgttattggtgtttatcataaacttggagaacgtgtacgccaagcta

tcttaaacactgttaaattttgtgaccacatggtcaaggctggtttagtcggtgtgctcacactagacaaccaggaccttaatggcaagtggtatgattttggtgacttcgtaatc

actcaacctggttcaggagtagctatagttgatagctactattcttatttgatgcctgtgctctcaatgaccgattgtctggccgctgagacacatagggattgtgattttaataaa

ccactcattgagtggccacttactgagtatgattttactgattataaggtacaactattgagaagtactttaaatattgggatcagacgtatcacgcaaattgcgttaattgtactg

atgaccgttgtgtgttacattgtgctaatttcaatgtattgtttgctatgaccatgcctaagacttgtttcggacccatagtccgaaagatctttgttgatggcgtgccatttgtagta

tcttgtggttatcactacaaagaattaggtttagtcatgaatatggatgttagtaccatagacataggctctctcttaaggagttgatgatgtatgccgctgatccagccatgca

cattgcctcctctaacgcttttcttgatttgaggacatcatgttttagtgtcgctgcacttacaactggtttgacttttcaaactgtgcggcctggcaattttaaccaagacttctatg

atttcgtggtatctaaaggtttctttaaggagggctcttcagtgacgctcaaacattttttctttgctcaagatggtaatgctgctattacagattataattactattcttataatctgcc

tactatgtgtgacatcaaacaaatgttgttctgcatggaagttgtaaacaagtacttcgaaatctatgacggtggttgtcttaatgcttctgaagtggttgttaataatttagacaa

gagtgctggccatccttttaataagtttggcaaagctcgtgtctattatgagagcatgtcttaccaggagcaagatgaactttttgccatgacaaagcgtaacgtcattcctacc

atgactcaaatgaatctaaaatatgctattagtgctaagaatagagctcgcactgttgcaggcgtgtccatacttagcacaatgactaatcgccagtaccatcagaaaatgctt

aagtccatggctgcaactcgtggagcgacttgcgtcattggtactacaaagttctacggtggctgggatttcatgcttaaaacattgtacaaagatgttgataatccgcatctta

tgggttgggattaccctaagtgtgatagagctatgcctaatatgtgtagaatcttcgcttcactcatattagctcgtaaacatggcacttgttgtactacaagggacagattttatc

gcttggcaaatgagtgtgctcaggtgctaagcgaatatgttctatgtggtggtggttactacgtcaaacctggaggtaccagtagcggagatgccaccactgcatatgccaa

tagtgtctttaacattttgcaggcgacaactgctaatgtcagtgcacttatgggtgctaatggcaacaagattgttgacaaagaagttaaagacatgcagtttgatttgtatgtca

atgtttacaggagcactagcccagaccccaaatttgttgataaatactatgatttcttaataagcacttttctatgatgatactgtctgatgacggtgtcgtttgctataatagtgat

tatgcagctaagggttacattgctggaatacagaattttaaggaaacgctgtattatcagaacaatgtctttatgtctgaagctaaatgctgggtggaaaccgatctgaagaaa

gggccacatgaattctgttcacagcatacgattatattaaggatggcgacgatggttacttccttccttatccagacccttcaagaattttgtctgccggttgattgtagatgat

atcgttaagactgacggtacactcatggtagagcggtttgtgtctttggctatagatgcttaccctctcacaaagcatgaagatatagaataccagaatgtattctgggtctactt

acagtatatagaaaaactgtataaagaccttacaggacacatgcttgacagttattctgtcatgctatgtggtgataattctgctaagttttgggaagaggcattctatagagatc

tctatagttcgcctaccactttgcaggctgtcggttcatgcgttgtatgccattcacagacttccctacgctgtgggacatgcatccgtagaccatttctctgctgtaaatgctgc

tatgatcatgttatagcaactccacataagatggttttgtctgtttctccttacgtttgtaatgcccctggttgtggcgtttcagacgttactaagctatatttaggtggtatgagcta

cttttgtgtagatcatagacctgtgtgtagttttccactttgcgctaatggtcttgtattcggcttatacaagaatatgtgcacaggtagtccttctatagttgaatttaataggttggc

tacctgtgactggactgaaagtggtgattacacccttgccaatactacaacagaaccactcaaactttttgctgctgagactttacgtgccactgaagaggcgtctaagcagt

cttatgctattgccaccatcaaagaaattgttggtgagcgccaactattacttgtgtgggaggctggcaagtccaaaccaccactcaatcgtaattatgtttttactggttatcat

ataaccaaaaatagtaaagtgcagctcggtgagtacattttcgagcgcattgattatagtgatgctgtatcctacaagtctagtacaacgtataaactgactgtaggtgacatct

tcgtacttacctctcactctgtggctaccttgacggcgcccacaattgtgaatcaagagaggtatgttaaaattactgggttgtacccaaccattacggtacctgaagagttcg

caagtcatgttgccaacttccaaaaatcaggttatagtaaatatgtcactgttcagggaccacctggcactggcaaaagtcattttgctatagggttagcgatttactaccctac

agcacgtgttgtttatacagcatgttcacacgcagctgttgatgattgtgtgaaaaagcttttaaatatttgaacattgctaaatgttcccgtatcattcctgcaaaggcacgtgtt

gagtgctatgacaggtttaaagttaatgagacaaattctcaatatttgtttagtactattaatgactaccagaaacttctgccgatattctggtggttgatgaggttagtatgtgca

ctaattatgatattcaattattaatgcacgtattaaagctaagcacattgtctatgtaggagatccagcacagttgccagctcctaggactttgttgactagaggcacattggaa

ccagaaaatttcaatagtgtcactagattgatgtgtaacttaggtcctgacatatttttaagtatgtgctacaggtgtcctaaggaaatagtaagcactgtgagcgctcttgtcta

caataataaattgttagccaagaaggagctttcaggccagtgctttaaaatactctataagggcaatgtgacgcatgatgctagctctgccattaatagaccacaactcacatt

tgtgaagaattttattactgccaatccggcatggagtaaggcagtctttatttcgccttacaattcacagaatgctgtgtctcgttcaatgctgggtcttaccactcagactgttga

ttcctcacagggttcagaataccagtacgttatcttctgtcaaacagcagatacggcacatgctaacaacattaacagatttaatgttgcaatcactcgtgcccaaaaaggtatt

ctttgtgttatgacatctcaggcactctttgagtccttagagtttactgaattgtatttactaattacaagctccagtctcagattgtaactggcctttttaaagattgctctagagaa

acttctggcctctcacctgcttatgcaccaacatatgttagtgttgatgacaagtataagacgagtgatgagctttgcgtgaatcttaatttacccgcaaatgtcccatactctcgt

gttatttccaggatgggctttaaactcgatgcaacagttcctggatatcctaagcttttcattactcgtgaagaggctgtaaggcaagttcgaagctggataggcttcgatgttg

agggtgctcatgcttcccgtaatgcatgtggcaccaatgtgcctctacaattaggattttcaactggtgtgaactttgttgttcagccagttggtgttgtagacactgagtgggg

taacatgttaacgggcattgctgcacgtcctccaccaggtgaacagtttaagcacctcgtgcctcttatgcataagggggctgcgtggcctattgttagacgacgtatagtgc

aaatgttgtcagacactttagacaaattgtctgattactgtacgtttgtttgttgggctcatggctttgaattaacgtctgcatcatacttttgcaagataggtaaggaacagaagt

gttgcatgtgcaatagacgcgctgcagcgtactcttcacctctgcaatcttatgcctgctggactcattcctgcggttatgattatgtctacaaccctttctttgtcgatgttcaaca

gtggggttatgtaggcaatcttgctactaatcacgatcgttattgctctgtccatcaaggagctcatgtggcttctaatgatgcaataatgactcgttgtttagctattcattcttgtt

ttatagaacgtgtggattgggatatagagtatccttatatctcacatgaaaagaaattgaattcctgttgtagaatcgttgagcgcaacgtcgtacgtgctgctcttcttgccggt

tcatttgacaaagtctatgatattggcaatcctaaaggaattcctattgttgatgaccagtggttgattggcattattttgatgcacagcccttgaccaggaaggtacaacagct

tttctatacagaggacatggcctcaagatttgctgatgggctctgcttattttggaactgtaatgtaccaaaatatcctaataatgcaattgtatgcaggtttgacacacgtgtgc

attctgagttcaatttgccaggttgtgatggcggtagtttgtatgttaacaagcacgcttttcatacaccagcatatgatgtgagtgcattccgtgatctgaaacctttaccattctt

ttattattctactacaccatgtgaagtgcatggtaatggtagtatgatagaggatattgattatgtacccctaaaatctgcagtagtattacagcttgtaatttagggggcgctgtt

tgtaggaagcatgctacagagtacagagagtatatggaagcatataatcttgtactgcatcaggtttccgcctttggtgttataagacctttgatatttataatctctggtctactt

ttacaaaagttcaaggtttggaaaacattgatttaatgttgttaaacaaggccattttattggtgttgagggtgaactacctgtagctgtagtcaatgataagatcttcaccaaga

gtggcgttaatgacatttgtatgtttgagaataaaaccactttgcctactaatatagcttttgaactctatgctaagcgtgctgtacgctcgcatcccgatttcaaattgctacaca

atttacaagcagacatttgctacaagttcgtcctttgggattatgaacgtagcaatatttatggtactgctactattggtgtatgtaagtacactgatattgatgttaattcagctttg

aatatatgttttgacatacgcgataattgttcattggagaagttcatgtctactcccaatgccatctttatttctgatagaaaaatcaagaaatacccttgtatggtaggtcctgatta

tgcttacttcaatggtgctatcatccgtgatagtgatgttgttaaacaaccagtgaagttctacttgtataagaaagtcaataatgagtttattgatcctactgagtgtatttacactc

agagtcgctcttgtagtgacttcctacccattctgacatggagaaagactttctatcttttgatagtgatgttttcattaagaagtatggcttggaaaactatgatttgagcacgt

agtctatggagacttctctcatactacgttaggcggtcttcacttgcttattggtttatacaagaagcaacaggaaggtcatattattatggaagaaatgctaaaaggtagctca

actattcataactattttattactgagactaacacagcggcttttaaggcggtgtgttctgttatagatttaaagcttgacgactttgttatgattttaaagagtcaagaccttggcgt

agtatccaaggttgtcaaggttcctattgacttaacaatgattgagtttatgttatggtgtaaggatggacaggttcaaaccttctaccctcgactccaggcttctgcagattgga

aacctggtcatgcaatgccatccctctttaaagttcaaaatgtaaaccttgaacgttgtgagcttgctaattacaagcaatctattcctatgcctcgcggtgtgcacatgaacatc

gctaaatatatgcaattgtgccagtatttaaatacttgcacattagccgtgcctgccaatatgcgtgttatacattttggcgctggttctgataaaggtatcgctcctggtacctca

gttttacgacagtggcttcctacagatgccattattatagataatgatttaaatgagttcgtgtcagatgctgacataactttatttggagattgtgtaactgtacgtgtcggccaa

caagtggatcttgttatttccgacatgtatgatcctactactaagaatgtaacaggtagtaatgagtcaaaggctttattctttacttacctgtgtaacctcattaataataatcttgct

cttggtgggtctgttgctattaaaataacagaacactcttggagcgttgaactttatgaacttatgggaaaatttgcttggtggactgttttctgcaccaatgcaaatgcatcctca

tctgaaggattcctcttaggtattaattacttgggtactattaaagaaaatatagatggtggtgctatgcacgccaactatatattttggagaaattccactcctatgaatctgagta

cttactcactttttgatttatccaagtttcaattaaaattaaaaggaacaccagttcttcaattaaaggagagtcaaattaacgaactcgtaatatctctcctgtcgcagggtaagtt

acttatccgtgacaatgatacactcagtgtttctactgatgttcttgttaacacctacagaaagttacgttgatgtagggccagattctgttaagtagcttgtattgaggttgatat

acaacagactttattgataaaacttggcctaggccaattgatgtttctaaggctgacggtattatataccctcaaggccgtacatattctaacataactatcacttatcaaggtct

ttttccctatcagggagaccatggtgatatgtatgtttactctgcaggacatgctacaggcacaactccacaaaagttgtttgtagctaactattctcaggacgtcaaacagtttg

ctaatgggtttgtcgtccgtataggagcagctgccaattccactggcactgttattattagcccatctaccagcgctactatacgaaaaatttaccctgatttatgctgggttctt

cagttggtaatttctcagatggtaaaatgggccgcttcttcaatcatactctagttcttttgcccgatggatgtggcactttacttagagctttttattgtattctagagcctcgctct

ggaaatcattgtcctgctggcaattcctatacttatttgccacttatcacactcctgcaacagattgttctgatggcaattacaatcgtaatgccagtctgaactcttttaaggagt

attttaatttacgtaactgcacctttatgtacacttataacattaccgaagatgagattttagagtggtttggcattacacaaactgctcaaggtgttcacctcttctcatctcggtat

gttgatttgtacggcggcaatatgtttcaatttgccaccttgcctgtttatgatactattaagtattattctatcattcctcacagtattcgttctatccaaagtgatagaaaagcttgg

gctgccttctacgtatataaacttcaaccgttaactttcctgttggatttttctgttgatggttatatacgcagagctatagactgtggttttaatgatttgtcacaactccactgctca

tatgaatccttcgatgttgaatctggagtttattcagtttcgtctttcgaagcaaaaccttctggctcagttgtggaacaggctgaaggtgttgaatgtgatttttcacctcttctgtc

tggcacacctcctcaggtttataatttcaagcgtttggtttttaccaattgcaattataatcttaccaaattgattcacttttttctgtgaatgattttacttgtagtcaaatatctccagc

agcaattgctagcaactgttattcttcactgattttggattacttttcatacccacttagtatgaaatccgatctcagtgttagttctgctggtccaatatcccagtttaattataaaca

gtccttttctaatcccacatgtttgattttagcgactgttcctcataaccttactactattactaagcctcttaagtacagctatattaacaagtgctctcgtcttattctgatgatcgta

ctgaagtacctcagttagtgaacgctaatcaatactcaccagtgtatccattgtcccatccactgtgtgggaagacggtgattattataggaaacaactatctccacttgaagg

tggtggctggcttgttgctagtggctcaactgttgccatgactgagcaattacagatgggctttggtattacagttcaatatggtacagacaccaatagtgtttgccccaagctt

gaatttgctaatgacacaaaaattgcctctcaattaggcaattgcgtggaatattccctctatggtgtttcgggccgtggtgtttttcagaattgcacagctgtaggtgttcgaca

gcagcgctttgtttatgatgcgtaccagaatttagttggctattattctgatgatggcaactactactgtttgcgtgcttgtgttagtgttcctgtttctgtcatctatgataaagaaac

taaaacccacgctactctatttggtagtgttgcatgtgaacacatttcttctaccatgtctcaatactcccgttctacgcgatcaatgcttaaacggcgagattctacatatggccc

ccttcagacacctgttggttgtgtcctaggacttgttaattcctctttgttcgtagaggactgcaagttgcctcttggtcaatctctctgtgctcttcctgacacacctagtactctca

cacctcgcagtgtgcgctctgttccaggtgaaatgcgcttggcatccattgatttaatcatcctattcaggttgatcaacttaatagtagttattttaaattaagtatacccactaat

ttttcctttggtgtgactcaggagtacattcagacaaccattcagaaagttactgttgattgtaaacagtacgtttgcaatggtttccagaagtgtgagcaattactgcgcgagta

tggccagttttgttccaaaataaaccaggctctccatggtgccaatttacgccaggatgattctgtacgtaatttgtttgcgagcgtgaaaagctctcaatcatctcctatcatac

caggttttggaggtgactttaatttgacacttctagaacctgtttctatatctactggcagtcgtagtgcacgtagtgctattgaggatttgctatttgacaaagtcactatagctga

tcctggttatatgcaaggttacgatgattgcatgcagcaaggtccagcatcagctcgtgatcttatttgtgctcaatatgtggctggttacaaagtattacctcctcttatggatgt

taatatggaagccgcgtatacttcatctttgcttggcagcatagcaggtgttggctggactgctggcttatcctcctttgctgctattccatttgcacagagtatcttttataggtta

aacggtgttggcattactcaacaggttattcagagaaccaaaagcttattgccaataagtttaatcaggctctgggagctatgcaaacaggcttcactacaactaatgaagct

tttcagaaggttcaggatgctgtgaacaacaatgcacaggctctatccaaattagctagcgagctatctaatacttttggtgctatttccgcctctattggagacatcatacaac

gtcttgatgttctcgaacaggacgcccaaatagacagacttattaatggccgtttgacaacactaaatgatttgttgcacagcagcttgttcgttccgaatcagctgactttcc

gctcaattggctaaagataaagtcaatgagtgtgtcaaggcacaatccaagcgttctggattttgcggtcaaggcacacatatagtgtcctttgttgtaaatgcccctaatggc

ctttacttcatgcatgttggttattaccctagcaaccacattgaggttgtttctgcttatggtattgcgatgcagctaaccctactaattgtatagcccctgttaatggctactttatt

aaaactaataacactaggattgttgatgagtggtcatatactggctcgtccttctatgcacctgagcccattacctcccttaatactaagtatgttgcaccacaggtgacatacc

aaaacatttctactaacctccctcctcctcttctcggcaattccaccgggattgacttccaagatgagttggatgagtttttcaaaaatgttagcaccagtatacctaattttggttc

cctaacacagattaatactacattactcgatcttacctacgagatgttgtacttcaacaagttgttaaagccdtaatgagtcttacatagaccttaaagagcttggcaattatact

tattacaacaaatggccgtggtacatttggcttggtttcattgctgggcttgttgccttagctctatgcgtcttcttcatactgtgctgcactggttgtggcacaaactgtatggga

aaacttaagtgtaatcgttgttgtgatagatacgaggaatacgacctcgagccgcataaggttcatgttcactaattaacgaactattaatgagagttcaaagaccacccactc

tcttgttagtgttttcactctctatttggtcactgcatcctcaaaacctctctatgtacctgagcattgtcagaattattctggttgcatgcttagggcttgtattaaaactgcccaag

ctgatacagaggtattatacaaattttcgaattgacgtcccatctgcagaatcaactggtactcaatcagtttctgtcgatcttgagtcaacttcaactcatgatggtcctaccg

aacatgttactagtgtgaatattttgacgttggttactcagttaattaacgaactctatggattacgtgtactgcttaatcaaatttggcagaagtaccttaactcaccgtatacta

cttgtttgtacatccctaaacccacagctaagtatacacctttagttggcacttcattgcaccctgtgctgtggaactgtcagctatcctttgctggttatactgaatctgctgttaat

tctacaaaagattggccaaacaggacgcagctcagcgaatcgcttggttgctacataaggatggaggaatccctgatggatgttccctctacctccggcactcaagtttatt

cgcgcaaagcgaggaagaggagccattaccaactaagaaactgcgctacgttaagcgtagattttctcttctgcgccatgaagaccttagtgttattgtccaaccaacaca

ctatgtcagggttacattttcagaccccaacatgtggtatctacgttcgggtcatcatttacactcagttcacaattggcttaaaccttatggcggccaacctgtttctgagtacca

tattactctagattgctaaatctcactgatgaagatttagctagagatttttcacccattgcgctattttgcgcaatgtcagatttgagctacatgagttcgccttgctgcgcaaa

actcttgttcttaatgcatcagagatctactgtgctaacatacatagatttaagcctgtgtatagagttaacacggcaatccctactattaaggattggcttctcgttcagggatttt

ccdttaccatagtggcctccattacatatgtcaatctctaaattgcatgcactggatgatgttactcgcaattacatcattacaatgccatgctttagaacttaccdcaacaaat

gtttgttactcctttggccgtagatgttgtctccatacggtcttccaatcagggtaataaacaaattgttcattcttatcccattttacatcatccaggattttaacgaactatggcttt

ctcggcgtctttatttaaacccgtccagctagtcccagtttctcctgcatttcatcgcattgagtctactgactctattgttttcacatacattcctgctagcggctatgtagctgatt

agctgtcaatgtgtgtctcattcccctattattactgctacgtcaagatacttgtcgtcgcagcattatcagaactatggttctctatttccttgttctgtataactttttattagccattg

tactagtcaatggtgtacattatccaactggaagttgcctgatagccttcttagttatcctcataatactttggtttgtagatagaattcgtttctgtctcatgctgaattcctacattc

cactgtttgacatgcgttcccactttattcgtgttagtacagtttcttctcatggtatggtccctgtaatacacaccaaaccattatttattagaaacttcgatcagcgttgcagctgt

tctcgttgtttttatttgcactcttccacttatatagagtgcacttatattagccgttttagtaagattagcctagtttctgtaactgacttctccttaaacggcaatgtttccactgttttc

gtgcctgcaacgcgcgattcagttcctcttcacataatcgccccgagctcgcttatcgtttaagcagctctgcgctactatgggtcccgtgtagaggctaatccattagtctctc

tttggacatatggaaaacgaactatgttaccdttgtccaagaacgaatagggttgttcatagtaaactttttcatttttaccgtagtatgtgctataacactcttggtgtgtatggct

ttccttacggctactagattatgtgtgcaatgtatgacaggcttcaataccctgttagttcagcccgcattatacttgtataatactggacgttcagtctatgtaaaattccaggata

gtaaaccccctctaccacctgacgagtgggtttaacgaactccttcataatgtctaatatgacgcaactcactgaggcgcagattattgccattattaaagactggaactttgc

atggtccctgatctttctcttaattactatcgtactacagtatggatacccatcccgtagtatgactgtctatgtctttaaaatgtttgttttatggctcctatggccatcttccatggc

gctatcaatatttagcgccgtttatccaattgatctagatcccagataatctctggcattgtagcagctgtttcagctatgatgtggatttcctactttgtgcagagtatccggctg

tttatgagaactggatcatggtggtcattcaatcctgagactaattgccttttgaacgttccatttggtggtacaactgtcgtacgtccactcgtagaggactctaccagtgtaac

tgctgttgtaaccaatggccacctcaaaatggctggcatgcatttcggtgcttgtgactacgacagacttcctaatgaagtcaccgtggccaaacccaatgtgctgattgcttt

aaaaatggtgaagcggcaaagctacggaactaattccggcgttgccatttaccatagatataaggcaggtaattacaggagtccgcctattacggcggatattgaacttgca

ttgcttcgagcttaggctctttagtaagagtatcttaattgattttaacgaatctcaatttcattgttatggcatcccctgctgcacctcgtgctgtttcctttgccgataacaatgata

taacaaatacaaacctatctcgaggtagaggacgtaatccaaaaccacgagctgcaccaaataacactgtctcttggtacactgggcttacccaacacgggaaagtccctc

ttacctttccacctgggcagggtgtacctcttaatgccaattctacccctgcgcaaaatgctgggtattggcggagacaggacagaaaaattaataccgggaatggaattaa

gcaactggctcccaggtggtacttctactacactggaactggacccgaagcagcactcccattccgggctgttaaggatggcatcgtttgggtccatgaagatggcgccac

tgatgctccttcaacttttgggacgcggaaccctaacaatgattcagctattgttacacaattcgcgcccggtactaagcttcctaaaaacttccacattgaggggactggagg

caatagtcaatcatcttcaagagcctctagcttaagcagaaactcttccagatctagttcacaaggttcaagatcaggaaactctacccgcggcacttctccaggtccatctg

gaatcggagcagtaggaggtgatctactttaccttgatcttctgaacagactacaagcccttgagtctggcaaagtaaagcaatcgcagccaaaagtaatcactaagaaag

atgctgctgctgctaaaaataagatgcgccacaagcgcacttccaccaaaagtttcaacatggtgcaagcttttggtcttcgcggaccaggagacctccagggaaactttg

gtgatcttcaattgaataaactcggcactgaggacccacgttggccccaaattgctgagcttgctcctacagccagtgcttttatgggtatgtcgcaatttaaacttacccatca

gaacaatgatgatcatggcaaccctgtgtacttccttcggtacagtggagccattaaacttgacccaaagaatcccaactacaataagtggttggagcttcttgagcaaaata

ttgatgcctacaaaaccttccctaagaaggaaaagaaacaaaaggcaccaaaagaagaatcaacagaccaaatgtctgaacctccaaaggagcagcgtgtgcaaggta

gcatcactcagcgcactcgcacccgtccaagtgttcagcctggtccaatgattgatgttaacactgattagtgtcactcaaagtaacaagatcgcggcaatcgtttgtgtttgg

caaccccatctcaccatcgcttgtccactcttgcacagaatggaatcatgttgtaattacagtgcaataaggtaattataacccatttaattgatagctatgctttattaaagtgtgt

agctgtagagagaatgttaaagactgtcacctctgcttgattgcaagtgaacagtgccccccgggaagagctctacagtgtgaaatgtaaataaaaaatagctattattcaatt

agattaggctaattagatgatttgcaaaaaaaaaaaa

2410
hCoV-
attgtgagcgatttgcgtgcgtgcatcccgcttcactgatctcttgttagatattttgtaatctaaactttataaaaacatccactccctgtaatctatgcttgtgggcgtagattttt

OC43
catagtggtgtttatattcatttctgctgttaacagattcagccagggacgtgttgtatcctaggcagtggcccgcccataggtcacaatgtcgaagatcaacaaatacggtct

genome
cgaactacactgggctccagaatttccatggatgtttgaggacgcagaggagaagttggataaccctagtagttcagaggtggatatgatttgctccaccactgcgcaaaa

(Genbank
gctggaaacagacggaatttgtcctgaaaatcatgtgatggtggattgtcgccgacttcttaaacaagagtgttgtgtgcagtctagcctaatacgtgaaattgttatgaatgc

Accession
aagtccatatgatttggaggtgctacttcaagatgattgcagtcccgtgaagcagttttggttacaacccccttaggtatgtctttagaggcatgctatgtgagaggttgtaatc

No.
ctaaaggatggaccatgggtttgtttcggcgtagaagtgtgtgtaacactggtcgttgcactgttaataagcatgtggcctatcagttatatatgattgatcctgcaggtgtctgt

NC_
cttggtgcaggtcaattcgtgggttgggtcatacccttagcctttatgcctgtgcaatcccggaaatttattgttccatgggttatgtacttgcgtaagcgtggcgaaaagggtg

006213.1)
cttacaataaagatcatggacgtggcggttttggacatgtttatgattttaaagttgaagatgcttatgaccaggtgcatgatgagcctaagggtaagttttctaagaaggcttat

gctttaattagagggtatcgtggtgttaaaccacttctctatgtagaccagtatggttgtgattatactggtagtcttgcagatggcttagaggcttatgctgataagacattgcaa

gaaatgaaggcattatttcctacttggagtcaggaactcctttttgatgtaattgtggcatggcatgttgtgcgtgatccacgttatgttatgagattgcagagtgctgctactata

cgtagtgttgcatatgttgctaatcctactgaagacttgtgtgatggttctgttgttataaaagaacctgtgcatgtttatgcagatgactctattattttacgtcaatataatttagttg

acattatgagtcatttttatatggaggcagatacagttgtaaatgctttttatggtgttgctttgaaagattgcggttttgttatgcagtttggttacattgattgcgaacaagactcgt

gtgattttaaaggttggattcctggtaacatgatagatggttttgcttgcaccacttgtggtcatgtttatgaagtaggtgatttgatggcacaatcttcaggtgttttgcctgttaac

cctgtattgcatactaagagtgcagcaggctatggtggttttggttgtaaagattcttttactctgtatggccaaactgtagtttattttggaggttgtgtgtattggagtccagcac

gtaatatatggattcctatattaaaatcctagttaagtcatatgacagtttggtttatactggagttttaggttgcaaggctattgtaaaggaaacaaatctcatttgcaaagctttg

taccttgattatgttcaacacaagtgtggcaatttacaccaacgggagttgctaggtgtttcagatgtgtggcataaacaattgctattaaatagaggtgtttataaacctctgtta

gagaatattgattattttaatatgcggcgcgctaaatttagtttagaaacttttactgtttgtgcagatggctttatgccttttcttttagatgatttagttccacgcgcatattatttggc

agtaagtggtcaagcattttgtgattatgcagataaactttgccatgccgttgtgtctaagagtaaagagttacttgatgtgtctctggattattaggtgcagctatacattatttg

aattctaagattgttgatttggctcaacattttagtgattttggaacaagtttcgtttctaaaattgttcatttattaagacttttactactagcactgctcttgcatttgcatgggttttat

ttcatgttttgcatggtgcttatatagtagtggagagtgatatatattttgttaaaaacattcctcgttatgctagtgctgttgcacaagcatttcagagtgttgctaaagttgtactg

gactctttaagagttacttttattgatggcctttcttgttttaagattggacgtagaagaatttgtctttcaggcagaaaaatttatgaagttgagcgtggcttgttacattcatccca

attgccattagatgtttatgatttaaccatgcctagtcaagttcagaaagccaagcaaaaacctatttatttaaaaggttctggttctgatttttcattagcggatagtgtagttgaa

gttgttacaacttcacttacaccatgtggttattctgaaccacctaaagttgcagctaaaatttgcattgtggataatgtttatatggccaaggctggtgacaaatattaccctgttg

tggttgatgatcatgttggactcttggatcaagcatggagagttccttgtgctggaaggcgtgttacatttaaggaacagcctacagtaaaggagattataagcatgcctaag

attattaaggttttttatgagcttgacaacgattttaatactattttaaatactgcgtgtggagtgtttgaagtggatgatactgttgatatggaggaattttatgctgtggtgattgat

gccatagaagagaaactttaccatgtaaggagcttgaaggtgtaggtgctaaagttagtgcctttttacagaaattagaggataatcccctatttttatttgatgaggctggcg

aggaagttcttgctcctaaattgtattgtgcctttacagctcctgaagatgatgactttcttgaggaaagtgatgttgaagaagatgatgtagaaggtgaggaaactgatttaac

tgtcacaagtgctggacagccttgtgttgctagtgaacaggaggagtcttctgaagtcttagaggacactttggatgatggtccaagtgtggagacatctgattcacaagttg

aagaagatgtagaaatgtcggattttgttgatcttgaatctgtgattcaggattatgaaaatgtttgttttgagttttatactacagagccagaatttgttaaagttttgggtctgtatg

tgcctaaagcaactcgcaacaattgctggttgcgatcagttttggcagtgatgcagaaattgccctgtcaatttaaagataaaaatttgcaggatctttgggtgttatacaagca

acagtatagtcagttgtttgttgataccttggttaataagatacctgctaatattgtacttccacaaggtggttatgttgctgattttgcatattggtttttaaccttatgtgattggcag

tgtgttgcatactggaaatgcattaaatgtgatttagctcttaagcttaaaggcttggatgctatgttcttttatggtgatgttgtttcacatatatgcaagtgtggtgagtctatggta

cttattgatgttgatgtgccatttacagcccactttgctcttaaagataagttgttttgtgcatttattactaagcgtattgtgtataaagcagcttgtgttgtggatgttaatgatagtc

attctatggctgttgttgatggtaaacaaattgatgatcatcgtatcactagtattactagtgataagtttgattttattattgggcatggtatgtcattttcaatgactacttttgaaatt

gcccaattgtatggttcttgtataacacctaatgtgtgttttgttaaaggtgatataattaaagtatctaagcttgttaaagcagaagttgttgtaaaccctgctaatggccatatgg

cacatggtggtggtgttgcaaaagctattgcagtagcagctggacagcagtttgttaaagagactaccgatatggttaagtctaaaggagtttgtgctactggagattgttatg

tactacagggggcaaattatgtaaaactgtgcttaatgttgttggacctgatgcgagaacacagggtaaacaaagttatgtattgttagagcgtgtttataaacatcttaacaa

ctatgactgtgttgttacaactttgatctcagctggtatatttagtgtgccttctgatgtgtctttaacatatctacttggtactgctaagaaacaagttgttcttgttagcaataatcaa

gaggattttgatcttatttctaagtgtcagataactgctgttgagggcactaagaaattggcagcgcgtctttatttaatgttggacgttccattgtttacgaaacagatgctaata

agttgattttaatcaatgacgttgcatttgtttcgacatttaatgttttacaggatgttttatccttaagacatgatatagcacttgatgatgatgcacgaaccttcgttcagagcaat

gttgatgttgtacctgagggttggcgtgttgtcaataagttttatcaaattaatggtgttagaaccgttaagtattttgagtgtactggaggcatagatatatgcagccaggataa

agtttttggttatgtacagcagggtatttttaataaggctactgttgctcaaattaaagccttgtttttggataaagtggacatcttgctaactgttgatggtgttaatttcactaatag

gtttgtgcctgttggtgaaagttttggtaagagtctaggaaatgtgttttgtgatggagttaatgtcacgaagcataagtgtgatataaattataaaggtaaagtctttttccagttt

gataatctttctagtgaagatttaaaggctgtaagaagttcctttaattttgatcagaaggaattgcttgcctattacaacatgcttgttaattgttttaagtggcaggttgttgttaat

ggtaagtatttcacttttaagcaagctaataacaattgttttgttaatgtttcttgcttaatgctccagagtttgcatctgacatttaaaattgttcaatggcaagaggcatggcttga

atttcgttctggccgccctgctagatttgtagctttggttttggccaaaggtgggtttaaatttggagatcctgctgattctagagatttcttgcgtgttgtgtttagtcaagttgattt

gactggggcaatatgtgattttgaaattgcatgtaaatgtggtgtaaagcaggaacagcgtactggtaggacgctgttatgcattttggtacattgagtcgtgaagatcttga

gattggttataccgtggactgttcttgcggtaaaaagctaattcattgtgtacgatttgatgtaccatttttaatttgcagtaatacacctgctagtgtaaaattacctaagggtgta

ggaagtgcaaatatttttataggtgataaggttggtcattatgttcatgttaagtgtgaacaatcttatcagctttatgatgcttctaatgttaagaaggttacagatgttactggca

agttgtcagattgtctgtatcttaaaaatttgaaacaaacttttaaatcggtgttaaccacctattatttggatgatgttaagaaaattgagtataaacctgacttgtcacaatattatt

gtgacggaggtaagtattatactcagcgtattattaaagcccaatttaaaacattcgagaaagtagatggtgtgtatactaattttaaattgataggacacaccgtagtgacag

tcttaatgctaagttgggttttgatagctctaaagagtttgttgaatataagattactgagtggccaacagctacaggtgatgtggtgttggctactgatgatttgtatgttaagag

atatgagaggggttgtattacttttggtaaacctgttatatggttaagccatgagaaagcttccctcaattattaacatattttaatagaccttcattggttgatgataataaatttga

tgttttaaaagtggatgatgttgacgatggtggtgacagctcagagagtggtgccaaagaaaccaaagaaatcaacattattaagttaagtggtgttaaaaaaccatttaagg

ttgaagatagtgtcattgttaatgatgatactagtgaaaccaaatatgttaagagtttgtctattgttgatgtgtatgatatgtggcttacaggttgtaagtatgttgttagaactgct

aatgattgagcagagcagttaacgtacctacaatacgtaagtttataaaatttggtatgactcttgttagtataccaattgatttgttaaatttaagagagattaagcctgctgtta

atgtggttaaagagtgcgaaataaaatttctgtatgattaatt-ttattaaatggctttttgtcttattatttggctggattaaaatatccgctgataataaagtaatctacaccacag

aaattgcatcaaagcttacgtgtaagcttgtagctttagcttttaaaaatgcatttttgacatttaagtggagtatggttgctagaggtgcttgcattatagcgactatatttctattgt

ggtttaattttatatatgccaatgtaatttttagtgatttttatttgcctaaaatcggtttcttgccgacttttgttggtaagattgcacagtggattaagaacacttttagtcttgtaacta

tttgtgatctatattccattcaggatgtgggttttaagaatcagtattgtaatggaagtattgcatgtcagttctgcttggcaggatttgatatgttagataattataaagccattgat

gtagtacagtatgaagctgataggagagcatttgttgattatacaggtgtgttaaagattgtcattgaattgatagttagttacgccctgtatacggcatggttttatccattgtttg

cccttatcagtattcagatcttgaccacttggctgcctgagctttttatgcttagtacattacattggagttttaggttgctggtggctttagctaatatgttaccagcacatgtgttta

tgaggttttatattattattgcctcttttattaagctctttagcttgtttaggcatgttgcctatggttgtagtaaatctggttgtttgttttgttacaagaggaatcgtagtctacgtgtta

aatgtagtactatcgttggtggcatgatacgctattacgatgttatggctaatggtggcactggcttttgttcaaaacatcaatggaattgcattgattgtgattcttataaaccag

gtaatacttttattactgttgaggccgctcttgatctatctaaggaattgaaacggcccattcagcctacagatgttgcttatcatacggttactgatgttaagcaagttggttgttc

tatgcgcttgttctatgatcgtgatggacagcgcacatatgatgatgttaatgctagtttgtttgtggattatagtaatttgctacattctaaggttaagagtgtgcctaatatgcatg

ttgtggtagtggaaaatgatgctgataaagccaattttctgaatgctgctgtattttatgcacagtctttgtttagacctattttaatggttgataaaaatctgataactactgctaac

actggtacgtctgttacagaaactatgtttgatgtttatgtggatacatttttgtctatgtttgatgtggataaaaagagtcttaatgattaatagcaactgcgcattatctataaaa

cagggtacgcagatttataaagttttggatacctttttaagctgtgctcgtaaaagttgttctattgattcagatgttgatactaagtgtttagctgattctgtcatgtctgctgtatcg

gcaggtcttgaattgacggatgaaagttgtaataacttggtgccaacatatttgaagagtgacaacattgtggcagctgatttaggtgttctgattcaaaattctgcaaagcatg

tgcagggtaatgttgctaaaatagctggtgtttcctgtatatggtctgtggatgcttttaatcagtttagttctgatttccagcataaattgaagaaagcatgttgtaaaactggtttg

aaactgaagcttacttataataagcagatggctaatgtctctgttttaactacaccattagtcttaaagggggtgcagtttttagttattttgtttatgtgtgttttgtgttgagtttggt

ctgttttattggactgtggtgcttaatgcccacttacacagtacacaaatcagattttcagcttcccgtttatgccagttataaagttttagataatggtgttattagagatgttagcg

ttgaagatgtttgtttcgctaacaaatttgaacaatttgatcaatggtatgagtctacatttggtctaagttattatagtaacagtatggcttgtcccattgttgttgctgtaatagatc

aggattttggctctacagtgtttaatgtccctaccaaagtgttacgatatggttatcatgtgttgcactttattacacatgcactttctgctgatggagtgcagtgttatacgccaca

tagtcaaatatcgtattctaatttttatgctagtggctgtgtgattcctctgcttgcactatgtttacaatggccgatggtagtccacaaccttattgttatacagaggggcttatgc

aaaatgcttactgtatagttcattggtacctcacgtgcggtataatcttgctaatgctaaaggttttatccgttttccagaagtgttgcgagaagggcttgtacgtatcgtgcgta

ctcgttctatgtcgtattgcagagttggattatgtgaggaagctgatgagggtatatgattaattttaatggttcttgggtgcttaataatgattattatagatcattgcctgggacc

ttttgtggtagagatgtttttgatttaatttatcagctatttaaaggtttagcacagcctgtggattttttggcattgactgctagttccattgctggtgctatactcgctgtaattgttgt

tttggtgttttattacctaataaagcttaaacgtgatttggtgattacaccagtgttgtttttgttaacgtgattgtgtggtgtgtaaattttatgatgctttttgtgtttcaagtttacccc

atactttcttgtgtatatgctatttgttatttttatgccacgattatttcccttcggagataagtgtgataatgcacttacaatggctagttatgtatggcactattatgcctttatggtttt

gtttgctatatatagctgttgttgtttcaaatcatgctttttgggtattttcttactgcagaaagcttggtacttctgttcgtagtgatggtacatttgaagaaatggctctcactactttt

atgattacaaaagattcttattgtaagcttaagaattctttgtctgatgttgatttaatagatatttgagtttgtataataaatataggtattacagcggtaaaatggatactgctgcat

atagggaggctgcttgctctcagttggctaaagcaatggacacatttaccaataataatggtagtgatgtgctttaccaaccgcctactgcttccgtctcaacttcattcttgcaa

tctggtattgtgaaaatggtaaatcctacttctaaggtagaaccatgtgttgtcagtgttacctatggtaatatgacattgaatggtttatggttggatgacaaggtctactgtccc

agacatgtaatatgttctgcttcagatatgactaatccagattatacaaatttgttgtgtagagtaacatcaagtgattttactgtattgtttgatcgtctaagccttacagtgatgtct

tatcaaatgcggggttgtatgcttgttcttacagtgaccdgcaaaattctcgtacgccaaaatatacatttggtgtggttaaacctggtgagacttttactgttttagctgcttata

acggcaaaccacaaggagcctttcatgtaactatgcgtagtagttataccattaagggttcctttttatgcggatcttgtggatctgttggttatgtaataatgggtgattgtgtta

aatttgtttatatgcatcaattggagcttagtactggttgtcatactggtactgacttcaatggggatttttatggtccttataaggatgctcaggttgttcagttgctcattcaggatt

atatacaatctgttaattttgtagcatggctttatgctgctatacttaacaattgtaattggtttgtacaaagtgataagtgttctgtagaagattttaatgtgtgggctctgtccaatg

gatttagccaagttaaatctgaccttgttatagatgctttagcttctatgactggtgtgtctttggaaacactgttggctgctattaagcgtcttaagaatggtttccaaggacgtca

gattatgggtagttgctcttttgaggatgaattgacacctagcgatgtttatcaacaactcgctggtatcaagttacaatcaaaacgcactagattgtttaaaggcactgtttgttg

gattatggcttctacatttttgtttagttgcataattacagcatttgtgaaatggactatgtttatgtatgtaactactaatatgtttagtattacgttttgtgcactttgtgttataagtttg

gccatgttgttggttaagcataagcatctttatttgactatgtatataactcctgtgctttttacactgttgtataacaactatttggttgtgtacaagcatacatttagaggctatgtct

atgcatggctatcatattatgttccatcagttgagtacacttatactgatgaagttatttatggcatgttattgcttgtaggaatggtattgttacattacgtagcattaaccatgattt

gttttcttttataatgtttgttggtcgtttgatttctgttttctctttgtggtacaagggttctaacttagaggaagaaattcttcttatgttggcttccctttttggtacttacacatggaca

acagttttatctatggctgtagcaaaggttattgctaagtgggttgctgtgaatgtcttgtatttcacagatatacctcaaattaagatagtgatttgtgctatttgtttattggttatat

tattagctgttattggggcttgttttccttgatgaacagtttgtttagaatgcctttgggtgtttataattataaaatttcagtacaggaattaagatatatgaatgctaatggattgcg

ccctcctaagaatagttttgaagcccttatgcttaattttaagagttgggtattggaggtgttccaatcattgaagtatctcaatttcaatcaaaattgactgatgtcaaatgtgcta

atgtcgtcttgcttaattgcttgcaacatttgcatgttgcttctaattctaagttgtggcattattgtagcactttgcacaatgaaatacttgccacttcggatctgagtgttgatttga

aaagcttgctcagttattaattgttttgtttgctaatccagctgctgtggatagcaagtgcctgactagtattgaagaagtttgcgatgattacgcaaaggacaatactgttttgca

ggctttacagagtgaatttgttaatatggctagcttcgttgaatatgaagttgctaagaaaaatcttgatgaggcgcgttttagtggttctgctaatcaacagcagttaaaacagc

tagagaaagcctgtaatattgctaaatctgcttatgaacgcgaccgtgctgtagcaaaaaagttggagcgtatggctgatttggctctcactaatatgtataaagaagctagaa

ttaatgataagaagagtaaggttgtttctgccttgcaaactatgctttttagtatggtgcgtaagttagataatcaagctctgaattcaatattagataacgctgtgaagggttgtgt

accattgaatgcaataccttcattggcagcaaatactctgaatataattgtaccagataaaagtgtttatgaccaggtagttgataatgtctatgttacctatgcgggtaatgtatg

gcagattcaaactatccaggattcagatggtacaaataagcagttgaatgagatatctgatgattgtaactggccactagttattattgcaaatcggtataatgaggtatctgct

actgttttgcaaaataatgaattaatgcctgctaagttgaaaattcaggttgttaatagtggtccagatcagacttgtaatacacctactcaatgttactataataatagtaacaatg

ggaagattgtttatgctatacttagtgatgttgatggtcttaagtatacaaaaattcttaaagatgatggcaattttgttgttttggagttagatcctccttgtaaatttactgttcaaga

tgctaaaggtcttaaaattaagtacctttattttgtaaaaggttgtaacacactagcaagaggctgggttgttggtacaatttcttctacagttagattgcaagctggaactgctac

tgaatatgcttccaactcatctatattgtattatgtgcgttttctgtagatcctaagaaaacgtatttagattttatacaacaaggaggaacacctattgccaattgtgttaaaatgtt

gtgtgaccatgctggtaccggtatggccattactgttaaacccgatgctaccactagtcaggattcatatggtggtgcgtctgtttgtatatattgccgcgcacgagttgaaca

cccagatgttgatgggttgtgcaaattacgcggcaagtttgtacaagtgcctgtaggtataaaagatcctgtgtcttatgttttgacacatgatgtttgtcgagtttgtggattttg

gcgggatggaagttgttcatgtgttagcactgacactactgttcaatcaaaagatactaattttttaaacgggttcggggtacgagtgtagatgcccgtctcgtaccctgcgcc

agtggtttatctactgatgtacaattaagggcatttgatatttacaatgctagtgttgctggcattggtttacatttaaaagttaattgttgccgttttcagcgtgttgatgagaacgg

tgataaattagatcagttattgttgttaagaggacagatctgactatatataatagagagatgaaatgctatgagcgtgtaaaagattgtaagtttgtggctgaacacgatttctt

tacatttgatgtagaaggtagtcgtgtgccacacattgtacgcaaggatttaacaaagtatactatgttggatctttgctatgcattgcgacattttgatcgcaatgattgcatgct

gctttgtgacattctctctatatatgctggttgtgaacaatcctactttactaagaaggattggtatgattttgttgaaaatcctgatattattaatgtgtataaaaagctaggacctat

ttttaatagagccctagttagcgctactgagtttgcggacaaattggtggaggtaggcttagtaggcgttttaacacttgataatcaagatttaaatggtaaatggtatgattttg

gtgactatgttattgcagccccaggatgtggtgttgctatagcagattcttattattcttatatcatgcctatgctgaccatgtgtcatgcattggattgcgaattgtatgtgaataat

gcttatagactatttgatcttgtacagtatgattttactgattacaagcttgaattgtttaataagtattttaagcactggagtatgccatatcatcctaacactgttgattgtcaggat

gatcggtgtattatacattgtgctaattttaacatactttttagtatggttttacctaatacatgttttgggcctcttgttaggcaaatttttgtggatggtgtgccttttgttgtttcaattg

gctaccattataaagaacttggtattgtgatgaatatggatgtggatacacatcgttatcgcttgtctttaaaagacttgatttatatgctgctgatccagctttgcatgtagcttct

gctagtgcattgtatgatttacgcacttgctgttttagtgttgccgctataacaagcggtgtaaaatttcaaacagttaaacctggtaattttaatcaggatttttatgattttgttttaa

gtaaaggcctgcttaaagagggtagctcagttgatctgaagcactttttattacacaggatggtaatgctgctattactgattataattattataagtataatttgcccaccatggt

ggacattaagcagttgttgtttgttttggaagttgtttataagtattttgagatttatgatggtgggtgtataccggcatcacaagtcattgttaataattatgataagagtgctggct

atccatttaacaaatttggaaaagccaggctctattatgaagcattatcatttgaggaacaggatgaaatttacgcttatactaagcgtaatgtcctgccaacacttactcaaatg

aatttgaaatatgctattagtgctaagaatagagcccgcactgttgctggtgtttccatacttagtactatgactggcagaatgtttcatcaaaaatgtttgaaaagtatagcagct

acacgtggtgttcctgtagttataggcaccactaaattttatggtggctgggatgatatgttacgccgccttattaaagatgttgacaatcctgtacttatgggttgggattatcct

aagtgtgatcgtgctatgccaaacctactacgtattgttagtagtttggtattagcccgaaaacatgagacatgttgttcgcaaagcgataggttttatcgacttgcgaatgaat

gcgcacaagttttgagtgaaattgttatgtgtggtggctgttattatgttaagcctggtggcactagtagtggtgatgcaactactgcttttgctaattcagtctttaacatatgtca

agagtttcagccaatgtatgtgccttaatgtcatgcaatggcaataagattgaagatcttagtatacgtgctcttcagaagcgcttatactcacatgtgtatagaagtgataagg

ttgattcaacctttgtcacagaatattatgaatttttaaataagcattttagtatgatgattttgagtgatgatggggttgtgtgttataattctgattatgcgtccaaagggtatattgc

taatataagtgcctttcaacaggtattatattatcaaaataacgtttttatgtcagaatccaaatgttgggttgaacatgacataaataatggacctcatgaattctgttcacaacac

acaatgcttgtaaagatggatggtgacgatgtctaccttccatatcctaatcctagtcgtatattaggagaggatgttttgtagatgatttgttaaagactgatagtgttcttttaat

agaacgatttgtaagtcttgcaatagatgcttatccacttgtgtatcatgaaaatgaagaataccaaaaggtttttcgtgtttatttggcgtatataaagaagttgtacaatgacct

gggtaatcagatcttggatagctacagtgttattttaagtacttgtgatggacaaaagttcactgatgagtccttttacaagaacatgtatttaagaagtgcagttatgcagagtg

ttggagcttgcgtggtctgctcttctcaaacatcattacgttgtggcagttgcatcagaaagcctcttctttgctgcaagtgttgttatgatcatgttatggcgactgatcataaata

tgtcttgagtgtttcaccatatgtgtgtaatgcaccaggatgtgatgtaaatgatgttaccaaattgtatctaggtggtatgtcatattattgtgaagaccataagccacaatattca

ttcaagttggtaatgaatggtaggtttttggtctatataaacaatcttgtacaggatctccgtacatagacgattttaatcgtatagctagttgtaaatggaccgatgtggatgatt

acatactagctaatgaatgtacagagcgcttgaaattgtttgctgcagaaacgcaaaaggcaaccgaggaagcctttaagcagagttatgcatcagcaacaatacaagaga

ttgttagtgagcgcgaattgattctctcttgggagattggaaaagttaagccaccacttaataaaaattatgtttttactggctaccattttactaaaaatggtaagacagttttagg

tgagtatgtttttgataagagtgagttgactaatggtgtgtattatcgcgccacaaccacttataagctatctgtaggagatgtttttgttttaacctctcattcagtagctaatttaa

gtgctcctacgcttgttccgcaggagaattatagtagtattagatttgctagtgtttatagtgtgcttgagacgtttcagaacaatgttgttaattatcaacacattggtatgaaacg

ttactgcaccgtgcaaggacctcctggtacagggaagtcacatcttgctattggtcttgctgtattctattgtacagcacgtgttgtatacacagcggccagccatgcagctgtt

gacgcattgtgtgaaaaagcatataaatttttgaatataaatgattgcactcgtattgttccggccaaggtcagggtggagtgctatgataagtttaaaattaatgacaccactc

gtaagtatgtgtttactaccataaatgcattacctgagatggtgactgatattgttgttgtagatgaagttagtatgcttaccaattatgagctttctgttattaatgctcgtattcgcg

ctaagcattatgtttatattggtgatcctgctcaattgccagcaccacgtgtgttattgagcaagggtacacttgaacctaaatattttaacactgttactaagctcatgtgttgctt

agggccagacatttttcttggtacatgttatagatgtcctaaggaaatcgttgatacagtgtccgccttggtttatgaaaataagcttaaggctaagaatgagagtagttcattgt

gttttaaggtctattataagggcgttacaacacatgaaagttctagtgctgtaaatatgcagcagatttatttgattaataagtttttgaaggctaaccattgtggcataaagctgt

ttttattagcccatataatagtcagaactttgcagctaagcgtgttttgggtttacaaacccaaaccgtggattctgctcaaggttctgaatatgattatgttatatattcacagact

gcagaaacagcgcattctgtaaatgttaatcgcttcaatgttgctattactcgagccaagaaaggtattctttgtgttatgagtaatatgcagttgtttgaagcattacagtttacta

cattgaccttagataaagtgccacaggccgtcgaaactaaagttcaatgtagtactaatttatttaaagattgtagcaagagttatagcggttatcacccagctcatgctccttca

tttttggcagtagatgacaaatataaggcaactggcgatttagccgtgtgtcttggtattggtgattctgctgttacatattcaagattaatatcactcatgggttttaaattggatgt

tacccttgatgggtattgtaagctttttataactaaagaagaagagttaaacgcgtgcgtgcctgggttggctttgatgctgaaggtgctcatgccacgcgtgatagcattgg

gacaaatttcccacttcaattaggattttccacaggaattgattttgttgtggaagccactggtttgtttgctgatagagatggttacagctttaaaaaggctgtggcgaaagctc

ctcctggtgaacaatttaagcacctcatccattgatgacgagaggtcatcgctgggatgttgttagacctagaatagtacaaatgtttgcagatcatttaattgatctgtctgatt

gtgttgtgctagttacatgggcagccaactttgagctcacttgtaccgctactttgcaaaagtagggcgtgagatttcttgtaatgtatgcactaaacgtgccacagtttacaat

tctagaactggttactatggttgttggcgccatagtgttacatgtgattacttgtataatccacttattgttgatattcaacagtggggatatattggttattatcaagtaatcatgatt

tatattgtagtgtccataaaggagcacatgttgcttcctctgatgctataatgacacggtgtttggccgtttatgattgatttgcaataatattaattggaatgtggagtatcccatc

atttcaaatgagttaagtattaatacctcttgtagggtcttgcagcgtgtgattcttaaagctgccatgctctgcaacagatatactttgtgttatgatattggcaacccaaaagcg

attgcctgtgtcaaagattttgattttaagttctatgatgcccaaccaattgttaagtctgttaagactcttttgtattatttgaggcacataaggactcttttaaagacggtttgtgta

tgttttggaactgtaatgtggataagtatccaccgaatgcagttgtatgtagatttgacactagagtgttgaataatttaaatcttcctggctgtaatggaggtagtttgtatgttaat

aaacatgcattccacactaaaccattgctagggcagcctttgagcatttgaagcctatgccattcttctattattcagatacgccttgtgtgtatatggatggcatggatgctaa

gcaggttgattatgtacctttgaaatctgccacgtgcatcacaagatgcaatttaggtggtgcagtttgtttaaaacatgctgaagagtatcgtgagtacttagagtcttacaata

cagctactacagcaggttttactttttgggtctataagacatttgatttttataatttgtggaatacgttcaccaagctacaaagcttggagaatgttgtatataatttagtcaagact

ggtcattatacaggacaggctggtgaaatgccttgtgccattataaatgataaagttgtggctaagatcgataaggaggatgttgtcatttttattaataatacaacataccctac

taatgtggccgttgaattatttgccaagcgcagtgttcgacaccacccagagcttaagctctttagaaatttaaatatagacgtgtgttggaagcacgtcatttgggattatgct

agagaaagtatattttgcagtaatacctatggtgtctgcatgtatacagatttaaagttcattgataaattgaatgtcctttttgatggtcgtgataatggtgctcttgaagcttttaa

acgttctaataatggcgtttacatttccacgacaaaagttaagagtctttcgatgataagaggtccaccgcgtgctgaattaaatggcgtagtggtggacaaggttggagaca

ctgattgtgtgttttattttgctgtgcgtaaagaaggtcaggatgtcatcttcagccaattcgacagcctgggagtcagctctaaccagagcccacaaggtaatctggggagt

aatggtaaacccggtaatgtcggtggtaatgatgactgtcaatctctactatctttacacaaagccgtgttattagctcttttacatgtcgtactgatatggaaaaagattttatag

ctttagatcaagatgtgtttattcagaagtatggtttggaggactatgcctttgaacacattgtttatggtaacttcaaccagaagattattggtggtttgcatttgttaataggcttg

taccgaagacagcaaacttccaatctggttgttcaggagtttgtttcatatgactccagcatacactcttattttatcactgacgagaagagtggtggtagtaagagtgtttgcac

tgttatagatattttgttggatgattttgtggctcttgttaagtcacttaatcttaattgtgtgagtaaggttgttaatgttaatgttgattttaaagattttcagtttatgattggtgtaac

gatgagaaagttatgactttctatcctcgtttgcaagctgcatctgactggaagcctggttattctatgcctgtattatataagtatttgaattctccaatggaaagagttagtctct

ggaattatgggaagccagttactttgcctacaggctgtatgatgaatgttgctaagtatactcagttatgtcaatatctgaatactacaacattagctgtacctgttaatatgcga

gttttgcatttaggtgcaggttcagaaaaaggagtagcaccgggttctgcagttcttaggcagtggttgcctgctggtactattcttgtagataacgatttatacccatttgttagt

gacagtgtcgctacatattttggggattgtataactttaccattgattgtcaatgggatttgataatttctgatatgtatgaccctattactaagaacataggggagtacaatgtga

gtaaagatggtttctttacatacatttgtcatatgattcgagacaagttagctctgggtggcagtgttgctataaaaataacagagttttcttggaatgcagaattatataagttaat

ggggtattttgcattttggactgtgttttgcacaaatgcaaatgcttcttctagtgaaggatttttaattggcataaattatttgtgtaagcccaaggttgagatagatggaaatgtta

tgcatgccaattatttgttttggagaaattccacagtttggaacgggggtgcttatagcctgtttgatatggctaaattcccgcttaagttggctggtactgccgtaataaatttaa

gagcagaccagattaatgatatggtttattcccttcttgaaaagggtaaactacttattagagatacaaataaagaagt-tttcgttggtgacagtttggttaatgtaatctaaacttt

aaaaatggctgtcgcttatgcagacaagcctaatcattttatcaattttccacttacccattttcagggttttgtgttaaattataaaggtttacaatttcaaattctcgatgaaggagt

ggattgtaaaatacaaacagcgccacacattagtcttactatgctggacatacagcctgaagactataaaagtgttgatgtcgctattcaagaagttattgatgatatgcattgg

ggtgatggttttcagattaaatttgagaatcctcacatcctaggaagatgcatagttttagatgttaaaggtgtagaagaattgcatgacgatttagttaattacattcgtgataaa

ggttgtgttgctgaccaatccaggaaatggattggccattgcaccatagctcaactcacggatgcagcactgtccattaaggaaaatgttgattttataaacagcatgcaattc

aattataaaatcaccatcaacccctcatcaccggctagacttgaaatagttaagctcggtgctgaaaagaaagatggtttttatgaaaccatagttagtcactggatgggaatt

cgttttgaatacacatcacccactgataagctagctatgattatgggttattgttgtttagatgtggtacgtaaagagctagaagaaggcgatcttcccgagaatgatgatgatg

cttggtttaagctatcgtaccattatgaaaacaattcttggttcttccgacatgtctacaggaaaagttttcatttccgtaaggcttgtcaaaatttagattgtaattgtttggggtttt

atgaatcttcagttgaagaatattaaactcagtgaaaatgtttttgcttcctagatttattctagttagctgcataattggtagcttaggtttttacaaccctcctaccaatgttgtttcg

catgtaaatggagattggtttttatttggtgacagtcgttcagattgtaatcatattgttaatatcaacccccataattattcttatatggaccttaatcctgttctgtgtgattctggta

aaatatcatctaaagctggcaactccatttttaggagttttcactttaccgatttttataattacacaggcgaaggtcaacaaattattttttatgagggtgttaattttacgccttatc

atgcctttaaatgcaaccgttctggtagtaatgatatttggatgcagaataaaggcttgttttatactcaggtttataagaatatggctgtgtatcgcagccttacttttgttaatgta

ccatatgtttataatggctccgcacaagctacagctctttgtaaatctggtagtttagtccttaataaccctgcatatatagctcctcaagctaactctggggattattattataagg

ttgaagctgatttttatttgtcaggttgtgacgagtatatcgtaccactttgtatttttaacggcaagtttttgtcgaatacaaagtattatgatgatagtcaatattattttaataaaga

cactggtgttatttatggtctcaattctacagaaaccattaccactggttttgatcttaattgttattatttagttttaccctctggtaattatttagccatttcaaatgagctattgttaac

tgttcctacgaaagcaatctgtcttaataagcgtaaggattttacgcctgtacaggttgttgattcgcggtggaacaatgccaggcagtctgataacatgacggcggttgcttg

tcaacctccgtactgttattttcgtaattctactaccaactatgttggtgtttatgatattaatcatggagatgctggttttactagcatacttagtggtttgttatataattcaccttgttt

ttcgcagcaaggcgtttttaggtatgataatgttagcagtgtctggcctctctacccctatggcagatgtcccactgctgctgatattaatatccctgatttacccatttgtgtgtat

gatccgctaccagttattttgcttggcattcttttgggcgttgcgattgtaattattgtagttttgttgttatattttatggtggataatgttactaggctgcatgatgcttagaccataat

ctaaacatgtttttgatacttttaatttccttaccaacggcttttgctgttataggagatttaaagtgtacttcagataatattaatgataaagacaccggtcctcctcctataagtact

gatactgttgatgttactaatggtttgggtacttattatgttttagatcgtgtgtatttaaatactacgttgtttcttaatggttattaccctacttcaggttccacatatcgtaatatggc

actgaagggaagtgtactattgagcagactatggtttaaaccaccatttattctgattttattaatggtatttttgctaaggtcaaaaataccaaggttattaaagatcgtgtaatgt

atagtgagttccctgctataactataggtagtacttttgtaaatacatcctatagtgtggtagtacaaccacgtacaatcaattcaacacaggatggtgataataaattacaaggt

cttttagaggtctctgtttgccagtataatatgtgcgagtacccacaaacgatttgtcatcctaacctgggtaatcatcgcaaagaactatggcatttggatacaggtgttgtttc

ctgtttatataagcgtaatttcacatatgatgtgaatgctgattatttgtattttcatttttatcaagaaggtggtactttttatgcatattttacagacactggtgttgttactaagtttttg

tttaatgtttatttaggcatggcgctttcacactattatgtcatgcctctgacttgtaatagtaagcttactttagaatattgggttacacctdcacttctagacaatatttactcgcttt

caatcaagatggtattatttttaatgctgttgattgtatgagtgattttatgagtgagattaagtgtaaaacacaatctatagcaccacctactggtgtttatgaattaaacggttaca

ctgttcagccaatcgcagatgtttaccgacgtaaacctaatcttcccaattgcaatatagaagcttggcttaatgataagtcggtgccctctccattaaattgggaacgtaagac

attttcaaattgtaattttaatatgagcagcctgatgtcttttattcaggcagactcatttacttgtaataatattgatgctgctaagatatatggtatgtgtttttccagcataactatag

ataagtttgctatacccaatggcaggaaggttgacctacaattgggtaatttgggctatttgcagtcatttaactatagaattgatactactgcaacaagttgtcagttgtattata

atttacctgctgctaatgtttctgttagcaggtttaatccttctacttggaataagagatttggttttatagaagattctgtttttaagcctcgacctgcaggtgttcttactaatcatga

tgtagtttatgcacaacactgtttcaaagctcctaaaaatttctgtccgtgtaaattgaatggttcgtgtgtaggtagtggtcctggtaaaaataatggtataggcacttgtcctgc

aggtactaattatttaacttgtgataatttgtgcactcctgatcctattacatttacaggtacttataagtgcccccaaactaaatctttagttggcataggtgagcactgttcgggt

cttgctgttaaaagtgattattgtggaggcaattcttgtacttgccgaccacaagcatttttgggttggtctgcagactcttgtttacaaggagacaagtgtaatatttttgctaattt

tattttgcatgatgttaatagtggtcttacttgttctactgatttacaaaaagctaacacagacataattcttggtgtttgtgttaattatgacctctatggtattttaggccaaggcatt

tttgttgaggttaatgcgacttattataatagttggcagaaccttttatatgattctaatggtaatctctacggttttagagactacataacaaacagaacttttatgattcgtagttgc

tatagcggtcgtgtttctgcggcctttcacgctaactcttccgaaccagcattgctatttcggaatattaaatgcaactacgtttttaataatagtcttacacgacagctgcaaccc

attaactattttgatagttatcttggttgtgttgtcaatgcttataatagtactgctatttctgttcaaacatgtgatctcacagtaggtagtggttactgtgtggattactctaaaaaca

gacgaagtcgtggagcgattaccactggttatcggtttactaattttgagccatttactgttaattcagtaaacgatagtttagaacctgtaggtggtttgtatgaaattcaaatac

cttcagagtttactataggtaatatggtggagtttattcaaacaagctctcctaaagttactattgattgtgctgcatttgtctgtggtgattatgcagcatgtaaatcacagttggtt

gaatatggtagtttctgtgataacattaatgccatactcacagaagtaaatgaactacttgacactacacagttgcaagtagctaatagtttaatgaatggtgttactcttagcact

aagcttaaagatggcgttaatttcaatgtagacgacatcaatttttcccctgtattaggttgtctaggcagcgaatgtagtaaagcttccagtagatctgctatagaggatttactt

tttgataaagtaaagttatctgatgtcggttttgttgaggcttataataattgtacaggaggtgccgaaattagggacctcatttgtgtgcaaagttataaaggcatcaaagtgttg

cctccactgctctcagaaaatcagatcagtggatacactttggctgccacctctgctagtctatttcctccttggacagcagcagcaggtgtaccattttatttaaatgttcagtat

cgcattaatgggcttggtgtcaccatggatgtgctaagtcaaaatcaaaagcttattgctaatgcatttaacaatgccctttatgctattcaggaagggttcgatgcaactaattc

tgattagttaaaattcaagctgttgttaatgcaaatgctgaagctcttaataacttattgcaacaactctctaatagatttggtgctataagtgcttctttacaagaaattctatctag

acttgatgctcttgaagcggaagctcagatagatagacttattaatggtcgtcttaccgctcttaatgcttatgtttctcaacagcttagtgattctacactggtaaaatttagtgca

gcacaagctatggagaaggttaatgaatgtgtcaaaagccaatcatctaggataaatttctgtggtaatggtaatcatattatatcattagtgcagaatgctccatatggtttgta

ttttatccactttagttatgtccctactaagtatgtcacagcgagggttagtcctggtctgtgcattgctggtgatagaggtatagctcctaagagtggttattttgttaatgtaaata

atacttggatgtacactggtagtggttactactaccctgaacctataactgaaaataatgttgttgttatgagtacctgcgctgttaattatactaaagcgccgtatgtaatgctga

acacttcaatacccaaccttcctgattttaaggaagagttggatcaatggtttaaaaatcaaacatcagtggcaccagatttgtcacttgattatataaatgttacattcttggacc

tacaagttgaaatgaataggttacaggaggcaataaaagtcttaaatcagagctacatcaatctcaaggacattggtacatatgaatattatgtaaaatggccttggtatgtatg

gatttaatctgccttgctggtgtagctatgcttgttttactattcttcatatgctgttgtacaggatgtgggactagttgttttaagaaatgtggtggttgttgtgatgattatactgga

taccaggagttagtaatcaaaacttcacatgacgactaagttcgtattgattcattgcactgatacttgttagatattttgcaatctagcatttgttaaagttcttaaggccacgc

cctattaatggacatttggagacctgagaagaaatatctccgttatattaacggttttaatgtctcagaattagaagatgcttgttttaaatttaactatcaatttcctaaagtaggat

attgtagagttcctagtcatgcttggtgccgtaatcaaggtagattttgtgctacattcactattatggtaaatccaaacattatgataaatattttggagtaataaatggtttcaca

gcattcgctaatactgtagaggatgctgttaacaaactggttttcttagctgttgactttattacctggcgcagacaggagttaaatgtttatggctgatgcttatcttgcagacac

tgtgtggtatgtggggcaaataatttttatagttgccatttgtttattggttacaatagttgtagtggcatttttggcaacttttaaattgtgtattcaactttgcggtatgtgtaatacct

tagtactgtccccttctatttatgtgtttaatagaggtaggcagttttatgagttttacaatgatgtaaaaccaccagtccttgatgtggatgacgtttaggtaatccaaacattatg

agtagtaaaactacaccagcaccagtttatatctggactgctgatgaagctattaaattcctaaaggaatggaatttttattgggtattatactactttttattacaatcatattgca

atttggatatacaagtcgcagtatgtttgtttatgttattaagatgattattttgtggcttatgtggccccttactataatcttaactattttcaattgcgtatacgcattgaataatgtgt

atcttggcctttctatagtttttaccatagtggccattattatgtggattgtgtattttgtgaatagtatcaggttgtttattagaactggaagtttttggagtttcaacccagaaacaaa

caacttgatgtgtatagatatgaaaggaacaatgtatgttaggccgataattgaggactatcatactctgacggtcacaataatacgcggccatctttacattcaaggtataaaa

ctaggtactggctattattggcagatttgccagcttatatgactgttgctaaggttacacacctgtgcacatataagcgtggttttcttgacaggataagcgatactagtggtttt

gctgtttatgttaagtccaaagtcggtaattaccgactgccatcaacccaaaagggttctggcatggacaccgcattgttgagaaataatatctaaattttaaggatgtatttac

tcctggtaagcaatccagtagtagagcgtcctctggaaatcgttctggtaatggcatcctcaagtgggccgatcagtccgaccagtttagaaatgttcaaaccaggggtaga

agagctcaacccaagcaaactgctacctctcagcaaccatcaggagggaatgttgtaccctactattcttggttctctggaattactcagtttcaaaagggaaaggagtttga

gtttgtagaaggacaaggtgtgcctattgcaccaggagtcccagctactgaagctaaggggtactggtacagacacaacagacgttatttaaaacagccgatggcaacc

agcgtcaactgctgccacgatggtatttttactatctgggaacaggaccgcatgctaaagaccagtacggcaccgatattgacggagtctactgggtcgctagcaaccagg

ctgatgtcaataccccggctgacattgtcgatcgggacccaagtagcgatgaggctattccgactaggtttccgcctggcacggtactccctcagggttactatattgaagg

ctcaggaaggtctgctcctaattccagatctacttcgcgcacatccagcagagcctctagtgcaggatcgcgtagtagagccaattctggcaatagaacccctacctctggt

gtaacacctgacatggctgatcaaattgctagtcttgttctggcaaaacttggcaaggatgccactaaacctcagcaagtaactaagcatactgccaaagaagtcagacaga

aaattttgaataagccccgccagaagaggagccccaataaacaatgcactgttcagcagtgttttggtaagagaggccctaatcagaattttggtggtggagaaatgttaaa

acttggaactagtgacccacagttccccattcttgcagaactcgcacccacagctggtgcgtttttattggatcaagattagagttggccaaagtgcagaatttatctgggaat

cctgacgagccccagaaggatgtttatgaattgcgctataacggcgcaattaggtttgacagtacactttcaggttttgagaccataatgaaggtgctgaatgagaatttgaat

gcctatcaacaacaagatggtatgatgaatatgagtccaaaaccacagcgtcagcgtggtcataagaatggacaaggagaaaatgataatataagtgttgcagtgcccaa

aagccgcgtgcagcaaaataagagtagagagttgactgcagaggacatcagccttcttaagaagatggatgagccctatactgaagacacctcagaaatataagagaat

gaaccttatgtcggcatctggtggtaacccctcgcagaaaagtcgagataaggcactctctatcagaatggatgtcttgctgctataatagatagagaaggttatagcagact

atagattaattagttgaaagttttgtgttgtaatgtatagtgttggagaaagtgaaagacttgcggaagtaattgccgacaagtgcccaagggaagagccagcatgttaagtta

ccacccagtaattagtaaatgaatgaagttaattatggccaattggaagaatcacaaaaaaaaaaaaaaaaaaaaaaaaaaaa

TABLE 4

Biological Assay Results for Assessed siNA

SARS-CoV-2 nanoluc
pSiCHECK-2 reporter
pSiCHECK-2 reporter assay Cos-7 at

hACE-2 A549 assay
assay Cos-7
least 50% inhibition

A: <0.1 nM EC50;
A: <0.2 nM EC50;
yes (y)/no (n)/undetermimed (u).

B: 0.1-1.0 nM EC50;
B: 0.2-1.0 nM EC50;
siRNAs w/>70% inhib. were followed

siNA Name
C: >1 nM EC50
C: >1 nM EC50
up w/EC50 (hACE-2 A549 assay)

ds-siNA-006

n

ds-siNA-007

n

ds-siNA-008

n

ds-siNA-009

n

ds-siNA-010

u

ds-siNA-011

B
y

ds-siNA-012

y

ds-siNA-013

n

ds-siNA-014

n

ds-siNA-015

n

ds-siNA-016

n

ds-siNA-017

n

ds-siNA-018

B
y

ds-siNA-019

y

ds-siNA-020

y

ds-siNA-021

y

ds-siNA-022

n

ds-siNA-023

n

ds-siNA-024

n

ds-siNA-025

u

ds-siNA-026

u

ds-siNA-027

y

ds-siNA-028

n

ds-siNA-029

n

ds-siNA-030

B
y

ds-siNA-031

n

ds-siNA-032

n

ds-siNA-033

u

ds-siNA-034

u

ds-siNA-035

n

ds-siNA-036

y

ds-siNA-037

n

ds-siNA-038

n

ds-siNA-039

A
y

ds-siNA-040

A
y

ds-siNA-041

y

ds-siNA-042

n

ds-siNA-043

n

ds-siNA-044

n

ds-siNA-045

n

ds-siNA-046

y

ds-siNA-047

y

ds-siNA-048

y

ds-siNA-049

n

ds-siNA-050

n

ds-siNA-051

B
y

ds-siNA-052

y

ds-siNA-053

n

ds-siNA-054

n

ds-siNA-055

n

ds-siNA-056

n

ds-siNA-057

u

ds-siNA-058

u

ds-siNA-059

u

ds-siNA-060

y

ds-siNA-061

B
y

ds-siNA-062

B
y

ds-siNA-063

n

ds-siNA-064

y

ds-siNA-065

y

ds-siNA-066

n

ds-siNA-067

B
y

ds-siNA-068

n

ds-siNA-069

n

ds-siNA-070

n

ds-siNA-071

n

ds-siNA-072

n

ds-siNA-073

n

ds-siNA-074

n

ds-siNA-075

C
y

ds-siNA-076

y

ds-siNA-077

n

ds-siNA-078

n

ds-siNA-079

u

ds-siNA-080

n

ds-siNA-081

A
y

ds-siNA-082

B
y

ds-siNA-083

B
y

ds-siNA-084

y

ds-siNA-085

y

ds-siNA-086

n

ds-siNA-087

A
y

ds-siNA-088

y

ds-siNA-089

B
y

ds-siNA-090

n

ds-siNA-091

n

ds-siNA-092

n

ds-siNA-093

n

ds-siNA-094

n

ds-siNA-095
B
B
y

ds-siNA-096

y

ds-siNA-097

n

ds-siNA-098

y

ds-siNA-099

n

ds-siNA-100

n

ds-siNA-101

n

ds-siNA-102

n

ds-siNA-103

n

ds-siNA-104

n

ds-siNA-105

u

ds-siNA-106

B
y

ds-siNA-107

y

ds-siNA-108

y

ds-siNA-109

n

ds-siNA-110

n

ds-siNA-111

n

ds-siNA-112

n

ds-siNA-113

y

ds-siNA-114

y

ds-siNA-115

B
y

ds-siNA-116

y

ds-siNA-117

n

ds-siNA-118

n

ds-siNA-119

y

ds-siNA-120

u

ds-siNA-121

u

ds-siNA-122

y

ds-siNA-123

n

ds-siNA-124

n

ds-siNA-125

B
y

ds-siNA-126

n

ds-siNA-127

n

ds-siNA-128

u

ds-siNA-129

u

ds-siNA-130

n

ds-siNA-131

y

ds-siNA-132

n

ds-siNA-133

n

ds-siNA-134

A
y

ds-siNA-135

A
y

ds-siNA-136

y

ds-siNA-137

n

ds-siNA-138

n

ds-siNA-139

n

ds-siNA-140

n

ds-siNA-141

n

ds-siNA-142

y

ds-siNA-143

y

ds-siNA-144

n

ds-siNA-145

n

ds-siNA-146

B
y

ds-siNA-147

n

ds-siNA-148

n

ds-siNA-149

n

ds-siNA-150

C
y

ds-siNA-151

n

ds-siNA-152

u

ds-siNA-153

u

ds-siNA-154

u

ds-siNA-155

y

ds-siNA-156

B
y

ds-siNA-157

B
y

ds-siNA-158

n

ds-siNA-159

y

ds-siNA-160

y

ds-siNA-161

n

ds-siNA-162

B
y

ds-siNA-163

n

ds-siNA-164

y

ds-siNA-165

y

ds-siNA-166

y

ds-siNA-167

y

ds-siNA-168

n

ds-siNA-169

n

ds-siNA-170
C
B
y

ds-siNA-171

y

ds-siNA-172

y

ds-siNA-173

B
y

ds-siNA-174

u

ds-siNA-175

y

ds-siNA-176
C
A
y

ds-siNA-177

A
y

ds-siNA-178

B
y

ds-siNA-179

B
y

ds-siNA-180

B
y

ds-siNA-181

y

ds-siNA-182

y

ds-siNA-183

A
y

ds-siNA-184

B
y

ds-siNA-185

n

ds-siNA-186

n

ds-siNA-187

n

ds-siNA-188

n

ds-siNA-189

n

ds-siNA-190

y

ds-siNA-191

y

ds-siNA-192

y

ds-siNA-193
B
B
y

ds-siNA-194

n

ds-siNA-195

n

ds-siNA-196
A
B

ds-siNA-197
B
B

ds-siNA-198
B
A

ds-siNA-199
A
B

ds-siNA-217

A

ds-siNA-218

A

ds-siNA-219

A

ds-siNA-220

A

ds-siNA-221

A

ds-siNA-222

A

SHORT INTERFERING NUCLEIC ACID (siNA) MOLECULES AND USES THEREOF FOR CORONAVIRUS DISEASES

Information

Publication Number

Date Filed

Date Published

Inventors

Original Assignees

CPC

International Classifications

Abstract

Description

Claims

CROSS-REFERENCE STATEMENT

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