Compositions and therapeutic methods for viral infection

Abstract

Methods for inhibiting viral propagation and treating viral infection are provided which include administering to cells infected with viruses a compound capable of inhibiting viral budding from the infected host cells.

Description

FIELD OF THE INVENTION

[0002] The present invention generally relates to pharmaceuticals and methods of treating diseases, particularly to methods and pharmaceutical compositions for treating viral infections.

BACKGROUND OF THE INVENTION

[0003] Viruses are the smallest of parasites, and are completely dependent on the cells they infect for their reproduction. Viruses are composed of an outer coat of protein, which is sometimes surrounded by a lipid envelope, and an inner nucleic acid core consisting of either RNA or DNA. Generally, after docking with the plasma membrane of a susceptible cell, the viral core penetrates the cell membrane to initiate the viral infection. After infecting cells, viruses commandeer the cell's molecular machinery to direct their own replication and packaging. The “replicative phase” of the viral lifecycle may begin immediately upon entry into the cell, or may occur after a period of dormancy or latency. After the infected cell synthesizes sufficient amounts of viral components, the “packaging phase” of the viral life cycle begins and new viral particles are assembled. Some viruses reproduce without killing their host cells, and many of these bud from host cell membranes. Other viruses cause their host cells to lyse or burst, releasing the newly assembled viral particles into the surrounding environment, where they can begin the next round of their infectious cycle.

[0004] Several hundred different types of viruses are known to infect humans, however, since many of these have only recently been recognized, their clinical significance is not fully understood. Of these viruses that infect humans, many infect their hosts without producing overt symptoms, while others (e.g., influenza) produce a well-characterized set of symptoms. Importantly, although symptoms can vary with the virulence of the infecting strain, identical viral strains can have drastically different effects depending upon the health and immune response of the host. Despite remarkable achievements in the development of vaccines for certain viral infections (i.e., polio and measles), and the eradication of specific viruses from the human population (e.g., smallpox), viral diseases remain as important medical and public health problems. Indeed, viruses are responsible for several “emerging” (or reemerging) diseases (e.g., West Nile encephalitis & Dengue fever), and also for the largest pandemic in the history of mankind (HIV and AIDS).

[0005] Viruses that primarily infect humans are spread mainly via respiratory and enteric excretions. These viruses are found worldwide, but their spread is limited by inborn resistance, prior immunizing infections or vaccines, sanitary and other public health control measures, and prophylactic antiviral drugs. Zoonotic viruses pursue their biologic cycles chiefly in animals, and humans are secondary or accidental hosts. These viruses are limited to areas and environments able to support their nonhuman natural cycles of infection (vertebrates or arthropods or both). However, with increased global travel by humans, and the likely accidental co-transport of arthropod vectors bearing viral payloads, many zoonotic viruses are appearing in new areas and environments as emerging diseases. For example, West Nile virus, which is spread by the bite of an infected mosquito, and can infect people, horses, many types of birds, and other animals, was first isolated from a febrile adult woman in the West Nile District of Uganda in 1937. The virus made its first appearance in the Western Hemisphere, in the New York City area in the autumn of 1999, and during its first year in North America, caused the deaths of 7 people and the hospitalization of 62. At the time of this writing (August, 2002) the virus has been detected in birds in 37 states and the District of Columbia, and confirmed human infections have occurred in Alabama, the District of Columbia, Florida, Illinois, Indiana, Louisiana, Massachusetts, Mississippi, Missouri, New York City, Ohio, and Texas. (See: http://www.cdc.gov/od/oc/media/wncount.htm).

[0006] Additionally, some viruses are known to have oncogenic properties. Human T-cell lymphotropic virus type 1 (a retrovirus) is associated with human leukemia and lymphoma. Epstein-Barr virus has been associated with malignancies such as nasopharyngeal carcinoma, Burkitt's lymphoma, Hodgkin's disease, and lymphomas in immunosuppressed organ transplant recipients. Kaposi's sarcoma-associated virus is associated with Kaposi's sarcoma, primary effusion lymphomas, and Castleman's disease (a lymphoproliferative disorder).

[0007] Treatment of viral diseases presents unique challenges to modern medicine. Since viruses depend on host cells to provide many functions necessary for their multiplication, it is difficult to inhibit viral replication without at the same time affecting the host cell itself. Consequently, antiviral treatments are often directed at the functions of specific enzymes of particular viruses. However, such antiviral treatments that specifically target viral enzymes (e.g., HIV protease, or HIV reverse transcriptase) often have limited usefulness, because resistant strains of viruses readily arise through genetic drift and mutation.

SUMMARY OF THE INVENTION

[0008] The present invention provides a method for inhibiting viral budding from virus-infected cells and thus inhibiting virus propagation in the cells. The method includes administering to the cells a compound comprising an amino acid sequence motif of PX1X2X3 and capable of binding a type I WW-domain of the cellular protein Nedd4 (neuronal precursor cell expressed developmentally downregulated 4), wherein X3 is Y or W or an analog thereof. The method is useful in the treatment of viral infections caused by viruses that utilize the Nedd4 protein or a Nedd4-like protein of their host cells for viral budding within and/or out of infected cells. The method can be used in treating virus infection caused by viruses such as hepatitis B virus, hepatitis E virus, human herpesviruses, Epstein-Barr virus, polyomavirus, Marburg virus, TT virus, lassa virus, lymphocytic choriomeningitis virus, vesicular stomatitis virus, and infectious pancreatic necrosis virus. In particular, the method is useful in the treatment of viral infections caused either hepatitis B virus or human herpesvirus 1. In addition, the method can also be useful in treating and preventing symptoms caused by and/or associated to viral infection.

[0009] In a first aspect of the invention, a method for treating viral infection is provided, which comprises administering to a patient in need of such treatment a composition comprising a peptide having an amino acid sequence motif PPXY, wherein X is an amino acid, and the peptide and is capable of binding a type I WW-domain of the Nedd4 protein. In preferred embodiments, X is proline (P), alanine (A), glutamic acid (E), asparagine (N), or arginine (R). Preferably, the peptide consists of from about 8 to about 100 amino acid residues, more preferably from 9 to about 50, or from 10 to about 20 amino acid residues.

[0010] In specific embodiments, the peptide includes a contiguous amino acid sequence of at least 6, preferably at least 8 amino acid residues, and more preferably from about 8 to about 30 or from about 9 to 20 amino acid residues of a viral protein selected from the group consisting of matrix proteins of rhabdoviruses, matrix proteins of filoviruses, Rous Sarcoma virus GAG protein, Mason-Pfizer Monkey virus GAG protein, hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, TT virus ORF2 protein; wherein said contiguous amino acid sequence encompasses the PPXY motif of the viral protein. Alternatively, the peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of Ebola virus Matrix (EbVp40) protein, Marburg virus matrix protein, VSV matrix protein, and Mason-Pfizer Monkey virus GAG protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein, wherein the peptide is capable of binding a type I WW-domain of Nedd4. For example, the peptide in the hybrid poly peptide can include an amino acid sequence selected from the group consisting of SEQ ID NOs:24-36, SEQ ID NOs:154-295, SEQ ID NOs:296-438, SEQ ID NOs:439-581, SEQ ID NOs:582-724, SEQ ID NOs:725-1010, SEQ ID NOs:1011-1296, SEQ ID NOs:1297-1439, SEQ ID NOs:1440-1452, SEQ ID NOs:1453-1491, SEQ ID NOs:1492-1530, and SEQ ID NOs:1531-1673.

[0011] In a specific embodiment, the peptide does not include a contiguous amino acid sequence of Ebola virus Matrix (EbVp40) protein that is sufficient to impart an ability to bind the UEV domain of the human Tsg101 protein.

[0012] In preferred embodiments, the peptide in the composition is associated with, or more preferably covalently linked to, a transporter that is capable of increasing the uptake of the peptide by a mammalian cell. In highly preferred embodiments the transporter increases uptake by at least 100%, preferably at least 300%. Advantageously, the transporter is selected from the group consisting of penetrating, l-Tat49-57, d-Tat49-57, retro-inverso isomers of l- or d-Tat49-57, L-arginine oligomers, D-arginine oligomers, L-lysine oligomers, D-lysine oligomers, L-histidine oligomers, D-histidine oligomers, L-ornithine oligomers, D-ornithine oligomers, and HSV-1 structural protein VP22 and fragments thereof, and peptides having at least six contiguous amino acid residues that are L-arginine, D-arginine, L-lysine, D-lysine, L-histidine, D-histidine, L-ornithine, D-ornithine, or a combination thereof; and peptoid analogs thereof. Alternatively, the transporter can be non-peptidic molecules or structures such as liposomes, dendrimers, and siderophores.

[0013] When a transporter covalently linked to a peptide of the present invention is peptidic transporter, a hybrid polypeptide is provided. In one embodiment, the hybrid polypeptide consists of from about 8 to about 100 amino acid residues, preferably from about 9 to about 50 amino acid residues. In preferred embodiments, the hybrid polypeptide consists of from about 12 to about 30 amino acid residues. In specific embodiments, X is either a proline (P), alanine (A), glutamic acid (E), asparagine (N), or an arginine (R).

[0014] Advantageously, the peptidic transporter in the hybrid polypeptide is capable of increasing the uptake of the peptide by a mammalian cell by at least 100%, preferably at least 300%. Examples of the peptidic transporter include penetrating, l-Tat49-57, retro-inverso isomers of l-Tat49-57, L-arginine oligomers, L-lysine oligomers, HSV-1 structural protein VP22 and fragments thereof, and peptides consisting of at least six contiguous amino acid residues that include two or more of the group consisting of L-arginine, L-lysine and L-histidine. However, in certain embodiments, the hybrid polypeptide does not contain a terminal L-histidine oligomer.

[0015] Various modifications may be made to improve the stability and solubility of the compound, and/or optimize its binding affinity to Nedd4, particularly to a type I WW domain of Nedd4. In particular, various protection groups can be incorporated into the amino acid residues of the compounds. In addition, the compounds according to the present invention can also be in various pharmaceutically acceptable salt forms.

[0016] The foregoing and other advantages and features of the invention, and the manner in which the same are accomplished, will become more readily apparent upon consideration of the following detailed description of the invention taken in conjunction with the accompanying examples, which illustrate preferred and exemplary embodiments.

DETAILED DESCRIPTION OF THE INVENTION

[0017] As used herein, the term “viral infection” generally encompasses infection of an animal host, particularly a human host, by one or more viruses. Thus, treating viral infection will encompass the treatment of a person who is a carrier of one or more specific viruses or a person who is diagnosed of active symptoms caused by and/or associated with infection by the viruses. A carrier of virus may be identified by any methods known in the art. For example, a person can be identified as virus carrier on the basis that the person is antiviral antibody positive, or is virus-positive, or has symptoms of viral infection. That is, “treating viral infection” should be understood as treating a patient who is at any one of the several stages of viral infection progression. In addition, “treating or preventing viral infection” will also encompass treating suspected infection by a particular virus after suspected past exposure to virus by e.g., blood transfusion, exchange of body fluids, bites, accidental needle stick, or exposure to patient blood during surgery, or other contacts with a person with viral infection that may result in transmission of the virus.

[0018] Specifically, as used herein, the term “HBV infection” generally encompasses infection of a human by any strain or serotype of hepatitis B virus, including acute hepatitis B infection and chronic hepatitis B infection. Thus, treating HBV infection means the treatment of a person who is a carrier of any strain or serotype of hepatitis B virus or a person who is diagnosed of active hepatitis B to reduce the HBV viral load in the person or to alleviate one or more symptoms associated with HBV infection and/or hepatitis B, including, e.g., nausea and vomiting, loss of appetite, fatigue, muscle and joint aches, elevated transaminase blood levels, increased prothrombin time, jaundice (yellow discoloration of the eyes and body) and dark urine. A carrier of HBV may be identified by any methods known in the art. For example, a person can be identified as HBV carrier on the basis that the person is anti-HBV antibody positive (e.g., based on hepatitis B core antibody or hepatitis B surface antibody), or is HBV-positive (e.g., based on hepatitis B surface antigen or HBV RNA or DNA) or has symptoms of hepatitis B infection or hepatitis B. That is, “treating HBV infection” should be understood as treating a patient who is at any one of the several stages of HBV infection progression. In addition, the term “treating HBV infection” will also encompass treating suspected infection by HBV after suspected past exposure to HBV by, e.g., contact with HBV-contaminated blood, blood transfusion, exchange of body fluids, “unsafe” sex with an infected person, accidental needle stick, receiving a tattoo or acupuncture with contaminated instruments, or transmission of the virus from a mother to a baby during pregnancy, delivery or shortly thereafter. The term “treating HBV infection” will also encompass treating a person who is free of HBV infection but is believed to be at risk of infection by HBV.

[0019] The term “preventing hepatitis B” as used herein means preventing in a patient who has HBV infection or is suspected to have HBV infection or is at risk of HBV infection from developing hepatitis B (which is characterized by more serious hepatitis-defining symptoms).

[0020] The terms “polypeptide,” “protein,” and “peptide” are used herein interchangeably to refer to amino acid chains in which the amino acid residues are linked by peptide bonds or modified peptide bonds. The amino acid chains can be of any length of greater than two amino acids. Unless otherwise specified, the terms “polypeptide,” “protein,” and “peptide” also encompass various modified forms thereof. Such modified forms may be naturally occurring modified forms or chemically modified forms. Examples of modified forms include, but are not limited to, glycosylated forms, phosphorylated forms, myristoylated forms, palmitoylated forms, ribosylated forms, acetylated forms, etc. Modified forms also encompass pharmaceutically acceptable salt forms. In addition, modifications also include intra-molecular crosslinking and covalent attachment to various moieties such as lipids, flavin, biotin, polyethylene glycol or derivatives thereof, etc. In addition, modifications may also include cyclization, and branching. Further, amino acids other than the conventional twenty amino acids encoded by genes may also be included in a polypeptide.

[0021] As used herein, the term “Nedd4” means human Nedd4 protein, unless otherwise specified.

[0022] The recruitment of cellular machinery to facilitate viral budding appears to be a general phenomenon, and distinct late domains have been identified in the structural proteins of several other enveloped viruses. See Vogt, Proc. Natl. Acad. Sci. USA, 97:12945-12947 (2000). Two well characterized late domains are the “PY” motif (consensus sequence: PPXY; X=any amino acid) found in membrane-associated proteins from certain enveloped viruses. See Craven et al., J. Virol., 73:3359-3365 (1999); Harty et al., Proc. Natl. Acad. Sci. USA, 97:13871-13876 (2000); Harty et al., J. Virol., 73:2921-2929 (1999); and Jayakar et al., J. Virol., 74:9818-9827 (2000). The cellular target for the PY motif is Nedd4, which also contains a Hect ubiquitin E3 ligase domain. The “YL” motif (YXXL) was found in the Gag protein of equine infectious anemia virus (EIAV). Puffer et al., J. Virol., 71:6541-6546 (1997); Puffer et al., J. Virol., 72:10218-10221 (1998). The cellular receptor for the “YL” motif appears to be the AP-50 subunit of AP-2. Puffer et al., J. Virol., 72:10218-10221 (1998). Interestingly, the late domains such as the P(T/S)AP motif, PY motif and the YL motif can still function when moved to different positions within retroviral Gag proteins, which suggests that they are docking sites for cellular factors rather than structural elements. Parent et al., J. Virol., 69:5455-5460 (1995); Yuan et al., EMBO J., 18:4700-4710 (2000). Moreover, the late domains such as the P(T/S)AP motif, PY motif and the YL motif can function interchangeably. That is one late domain motif can be used in place of another late domain motif without affecting viral budding. Parent et al., J. Virol., 69:5455-5460 (1995); Yuan et al., EMBO J., 18:4700-4710 (2000); Strack et al., Proc. Natl. Acad. Sci. USA, 97:13063-13068 (2000).

[0023] Nedd4 is a ubiquitin protein ligase containing a ubiquitin ligase Hect domain and several so-called WW domains. Specifically, the second and third WW-domains of Nedd4 are Type I WW-domains, which are found to bind to the PY motifs of a few viruses. The Hect ubiquitin E3 ligase domain transfers ubiquitin onto specific protein substrates and can “mark” surface receptors for endocytosis by monoubiquitination. See Harvey and Kumar, Trends Cell Biol., 9:166-169 (1999); Hicke, Trends Cell Biol., 9:107-112 (1999). The PY motif binds Nedd4 via one or more of the type I WW-domains in Nedd4. See Kanelis et al., Nat. Struct. Biol., 8:407-412 (2001); Lu et al., Science, 283:1325-1328 (1999).

[0024] Accordingly, while not wishing to be bound by any theory, it is believed that although the three late domain motifs bind to different cellular targets, they utilize common cellular pathways to effect viral budding. In particular, it is believed that the different cellular receptors for viral late domain motifs feed into common downstream steps of the vacuolar protein sorting (VPS) and MVB pathway. As is known in the art, all three cellular targets, i.e., Tsg101, Nedd4 and AP-2, function in the VPS pathway. Another protein, Vps4, functions in Tsg101 cycling and endosomal trafficking. Particularly, Vps4 mutants prevent normal Tsg101 trafficking and induce formation of aberrant, highly vacuolated endosomes that are defective in the sorting and recycling of endocytosed substrates. See Babst et al, Traffic, 1:248-258 (2000); Bishop and Woodman, J. Biol. Chem., 276:11735 (2001).

[0025] While not wishing to be bound by any theory, it is believed that the PY motif or a variation thereof enables a protein containing the PY motif to bind the cellular protein Nedd4, and that the binding of the PY motif in viral proteins to a type I WW-domain of Nedd4 or another cellular protein (e.g., a Nedd4-like cellular protein) enables viruses having the PY motif to usurp cellular machinery normally used for MVB formation to allow viral budding from the plasma membrane. Nedd4 and/or other Nedd4-like proteins may serve as the common docking site for all viruses that utilize the PY motif to bud off host cell cytoplasm membrane. It is also believed that depletion of Nedd4 or other Nedd4-like proteins or interfering with the interaction between Nedd4 (and/or other Nedd4-like proteins) and the PY motif in virus-infected cells will prevent viral budding from the cells.

[0026] In accordance with the present invention, a number of viral proteins have been found to also contain the PY motif. The proteins are summarized in Table 1 below.

TABLE 1
Viral Proteins Containing the P Y Motif
	PPPY-	GenBank
	Containing	Accession	SEQ ID
Virus	Protein	No.	NO:
Ebola Virus	Matrix Protein	AAL25816	27
Marburg Virus	VP40 Protein	NP_042027	28
Vesicular Stomatitis	Matrix Protein	P04876	29
Virus
Rous Sarcoma Virus	GAG Protein	AAA19608	30
Hepatitis B Virus
(Isolate Patient Usai ′89)	Core Antigen	S53155	31
Human Herpesvirus 4	Latent Membrane	CAA57375	32
(Epstein-Barr Virus)	Protein 2A
Human Herpesvirus 1	UL56 Protein	A43965	33
(Strain F)
Human Herpesvirus 7	Major Capsid	AAC40768	34
	Scaffold Protein
Infectious Pancreatic	Structural Protein	AAK18736	35
Necrosis Virus	VP2
Lassa Virus	Z Protein	AAC05816	36
Lymphocytic	Ring Finger Protein	CAA10342	37
Choriomeningitis Virus
TT Virus	ORF2	BAB19319	38

[0027] The inventors therefore propose using peptides containing a PY motif and capable of binding a type I WW-domain of Nedd4 or a Nedd4-like protein in treating viral infection, particularly infections caused by viruses that utilizes their PY motif in viral budding.

[0028] Thus, in accordance with a first aspect of the present invention, a method is provided for inhibiting viral budding from virus-infected cells and thus inhibiting virus propagation in the cells. The method includes administering to the cells a compound capable of binding to one or more type I WW-domains of Nedd4 or a Nedd4-like protein (e.g., E3 ubiquitin ligase).

[0029] Specifically, the method comprises administering to the cells a compound having an amino acid sequence motif of PX1X2X3, wherein X3 is Y or W or an analog thereof. In one embodiment, the X1 in the motif is P or an analog thereof. In a preferred embodiment, the compound administered has the amino acid sequence motif of PX1X2X3, wherein X1 is P or an analog thereof, and X3 is Y or W or an analog thereof. In a more preferred embodiment, X1 in the PX1X2X3 motif is P or an analog thereof, and X2 is P or an analog thereof, and X3 is Y or W or an analog thereof. In a most preferred embodiment, X1 in the PX1X2X3 motif is P or an analog thereof, and X2 is P or an analog thereof, and X3 is Y or an analog thereof. In preferred embodiments, the compounds are capable of binding a WW domain of Nedd4 or a Nedd4-like protein of a human cell. The compounds can be administered to cells in vitro or cells in vivo in a human or animal body. In the case of in vivo applications of the method, viral infection can be treated and alleviated by using the compound to inhibit virus propagation.

[0030] In preferred embodiments, the method comprises administering to cells a composition comprising a peptide having an amino acid sequence motif PPXY and capable of binding a type I WW-domain of the Nedd4 protein, wherein X is an amino acid.

[0031] The method of the present invention can be used for inhibiting viral budding by an enveloped virus. Advantageously, the method is used for inhibiting viral budding by viruses such as rhabdoviruses (e.g., vesicular stomatitis virus), filoviruses (e.g., Ebola virus and Marburg virus), Rous Sarcoma virus, hepatitis B virus (“HBV”), human herpesvirus 1 (HSV1), human herpesvirus 4 (HSV4), human herpesvirus 7 (HSV7), infectious pancreatic necrosis virus, Lassa virus, lymphocytic choriomeningitis virus, Epstein-Barr virus, polyomavirus, TT virus, etc. In a preferred embodiment, the method is applied to inhibit viral budding by hepatitis B virus, hepatitis E virus, and human herpes virus 1. By inhibiting viral budding in cells in a patient, the viral load in the patient body can be prevented from increasing and can even be decreased. Accordingly, the method of the present invention can also be used in treating viral infection as well as symptoms caused by and/or associated with the viral infection. In addition, when applied at an early stage before a patient develops a full-blown disease caused by viral infection, the method can be used to prevent such a disease by inhibiting viral propagation and decreasing the viral load in the patient. For example, human hepatitis B virus is known to cause hepatitis which may increase the risk of liver cancer. Thus, if the compounds of the present invention is applied to a patient at an early stage of the hepatitis B infection before the full-blown of hepatitis, hepatitis may be prevented and the likelihood of liver cancer in the patient may be reduced.

[0032] The compounds according to the present invention can be of any type of chemical compounds. For example, the compound can be a peptide, a modified peptide, an oligonucleotide-peptide hybrid (e.g., PNA), etc. In a preferred embodiment, the compound administered is capable of binding a type I WW-domain of human Nedd4 or a Nedd4-like protein. In a specific aspect of this embodiment, the compound is a peptide having a PPXY motif. Advantageously, X is selected from the group consisting of proline (P), alanine (A), glutamic acid (E), asparagine (N), and arginine (R).

[0033] Thus, the compounds can be a tetrapeptide, e.g., having an amino acid sequence of PX1X2X3 For example, the compounds can have an amino acid sequence of PPPY (SEQ ID NOs:1), PPAY (SEQ ID NO:2), PPNY (SEQ ID NO:3), PPRY (SEQ ID NO:4), all of which are derived from the rENaC P2 peptide. See Kanelis et al., Nat. Struct. Biol., 8:407-412 (2001).

[0034] The compound can also include a longer peptide comprising the amino acid sequence motif of PX1X2X3. For example, the compound may include a peptide of 5, 6, 7, 8 or 9 amino acids, preferably 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids. Advantageously, the compound is a peptide that contains an amino acid sequence of less than about 400, 375, 350, 325, 300, 275, 250, 225 or 200 residues. Preferably, the peptide contains an amino acid sequence of less than about 175, 150, 125, 115, 100, 95, 90, 85, 80, 75, 70, 65, 60 or 55 residues. More preferably, the peptide contains an amino acid sequence of less than about 50, 48, 45, 42, 40, 38, 35, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21 or 20 residues. In preferred embodiments, the peptide contains an amino acid sequence of from about 4 to about 200, 6 to about 150, 8 to about 100, preferably from about 8 to about 50, more preferably from about 9 to about 50, from about 9 to 45, 9 to 40, 9 to 37, 9 to 35, 9 to 30, 9 to 25 residues. More advantageously, the peptide contains an amino acid sequence of from 9 to about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 residues, even more advantageously, from 10 to about 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 residues. Preferably, the PX1X2X3 motif in the sequence is the PPXY motif.

[0035] Preferred examples of pentapeptides include but are not limited to PPPAY (SEQ ID NO:5), PPPNY (SEQ ID NO:6), and PPPRY (SEQ ID NO:7).

[0036] In one embodiment, the compound includes a peptide that contains a contiguous amino acid sequence of a naturally occurring rENaC P2 peptide sequence. The contiguous span should span at least one of the PY motifs of the rENaC P2 peptide. In another embodiment, the compound includes a peptide that contains a contiguous amino acid sequence of a naturally occurring peptide sequence of Rous sarcoma virus p2b, which contiguous sequence should span the PY motif in the p2b protein. In yet another embodiment, the compound includes a peptide that contains a contiguous amino acid sequence of a naturally occurring peptide sequence of Moloney murine leukemia virus (M-MuLV) p12 protein, which contiguous sequence should span the PY motif in the p12 protein. In yet another embodiment, the compound includes a peptide that contains a contiguous amino acid sequence of a naturally occurring peptide sequence of Mason-Pfizer money virus (M-PMV) pp24/16, which contiguous sequence should span the PY motif in the pp24/16 protein. See Yasuda and Hunter, J. Virol., 72:4095-4103 (1998).

[0037] In specific embodiments, the compound includes an amino acid sequence selected from the group of PPPNYD (SEQ ID NO:8), PPPNYDS (SEQ ID NO:9), PPPNYDSL (SEQ ID NO: 10), TPPPNY (SEQ ID NO: 11), TPPPNYD (SEQ ID NO: 12), TPPPNYDS (SEQ ID NO: 13), TPPPNYDSL (SEQ ID NO: 14), GTPPPNY (SEQ ID NO:15), PGTPPPNY (SEQ ID NO:16), GTPPPNYDS (SEQ ID NO: 17), GTPPPNYDSL (SEQ ID NO:18), PGTPPPNYDSL (SEQ ID NO: 19), IPGTPPPNYDSL (SEQ ID NO:20), PIPGTPPPNYDSL (SEQ ID NO:21), LPIPGTPPPNYDSL (SEQ ID NO:22), TLPIPGTPPPNYDSL (SEQ ID NO:23), GTPPPNYD (SEQ ID NO:24), PPPAYATL (SEQ ID NO:25), and PPPRYNTL (SEQ ID NO:26).

[0038] In another embodiment, the compound includes a contiguous amino acid sequence of a viral protein selected from the group consisting of matrix proteins of rhabdoviruses, matrix proteins of filoviruses, Rous Sarcoma virus GAG protein, Mason-Pfizer Monkey virus GAG protein, hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, and TT virus ORF2 protein, and wherein the contiguous amino acid sequence encompasses the PPXY motif of the viral protein.

[0039] In a specific embodiment, the compound includes a contiguous amino acid sequence of VSV matrix protein, Rous Sarcoma virus GAG protein or Mason-Pfizer Monkey virus GAG protein that encompasses the PPXY motif of the protein.

[0040] Advantageously, the compound is a peptide that contains a contiguous amino acid sequence of less than about 400, 375, 350, 325, 300, 275, 250, 225 or 200 residues of one of the viral proteins in Table 1, which encompasses the PPXY motif of the viral protein, and is capable of binding a Type I WW-domain of Nedd4. Preferably, the peptide contains a contiguous amino acid sequence of less than about 175, 150, 125, 115, 100, 95, 90, 85, 80, 75, 70, 65, 60 or 55 residues of one of the viral proteins in Table 1, which encompasses the PPXY motif of the viral protein, and is capable of binding a Type I WW-domain of Nedd4. More preferably, the peptide contains a contiguous amino acid sequence of less than about 50, 48, 45, 42, 40, 38, 35, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21 or 20 residues of one of the viral proteins in Table 1, which encompasses the PPXY motif of the viral protein, and is capable of binding a Type I WW-domain of Nedd4. In preferred embodiments, the peptide contains a contiguous amino acid sequence of from about 4 to about 50, preferably from about 6 to about 50, from about 8 to about 50, more preferably from about 9 to about 50, from about 9 to 45, 9 to 40, 9 to 37, 9 to 35, 9 to 30, 9 to 25 residues of one of the viral proteins in Table 1, which encompasses the PPXY motif of the viral protein, and is capable of binding a Type I WW-domain of Nedd4. More advantageously, the peptide contains a contiguous amino acid sequence of from 9 to about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 residues of a viral protein in Table 1, even more advantageously, from 10 to about 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 residues of one of the viral proteins in Table 1, which encompasses the PPXY motif of the viral protein, and is capable of binding a Type I WW-domain of Nedd4.

[0041] In specific embodiments, a peptide according to the present invention has a contiguous amino acid sequence of a viral protein in Table I as provided in SEQ ID NOs:39-153, SEQ ID NOs:154-295, SEQ ID NOs:296-438, SEQ ID NOs:439-581, SEQ ID NOs:582-724, SEQ ID NOs:725-1010, SEQ ID NOs:1011-1296, SEQ ID NOs:1297-1439, SEQ ID NOs:1440-1452, SEQ ID NOs:1453-1491, SEQ ID NOs:1492-1530, and SEQ ID NOs:1531-1673.

[0042] In another embodiment, the compound according to the present invention is within an amino acid sequence that is at least 70 percent, preferably at least 80 percent or 85 percent, more preferably at least 90 percent or 95 percent identical to a contiguous span of at least 5, 6, 7, 8 or 9 amino acids, preferably 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids of one of the proteins in Table 1, which contiguous span of amino acids spans the late domain motif PPXY. In another embodiment, the compound according to the present invention is within an amino acid sequence that is at least 70 percent, preferably at least 80 percent or 85 percent, more preferably at least 90 percent or 95 percent identical to a contiguous span of at least 5, 6, 7, 8 or 9 amino acids, preferably 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids of a naturally occuring Moloney murine leukemia virus (M-MuLV) p12 protein, which contiguous span of amino acids spans the late domain motif PPPY of p12. In yet another embodiment, the compound according to the present invention is within an amino acid sequence that is at least 70 percent, preferably at least 80 percent or 85 percent, more preferably at least 90 percent or 95 percent identical to a contiguous span of at least 5, 6, 7, 8 or 9 amino acids, preferably 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids of a naturally occuring Mason-Pfizer money virus (M-PMV) pp24/16, which contiguous span of amino acids spans the late domain motif PPPY of pp24/16. In this respect, the percentage identity is determined by the algorithm of Karlin and Altschul, Proc. Natl. Acad. Sci. USA, 90:5873-77 (1993), which is incorporated into the various BLAST programs. Specifically, the percentage identity is determined by the “BLAST 2 Sequences” tool, which is available at http://www.ncbi.nlm.nih.gov/gorf/bl2.html. See Tatusova and Madden, FEMS Microbiol. Lett., 174(2):247-50 (1999). For pairwise protein-protein sequence comparison, the BLASTP 2.1.2 program is employed using default parameters (Matrix: BLOSUM62; gap open: 11; gap extension: 1; x_dropoff: 15; expect: 10.0; and wordsize: 3, with filter). Preferably, such homologue peptides retain the ability to bind a type I WW-domain of Nedd4 or a Nedd4-like protein. Preferably, in such embodiments of the present invention, X1 in the PX1X2X3 motif is P or an analog thereof. More preferably, X1 is P or an analog thereof, and X3 is Y or W or an analog thereof. Most preferably, X1 is P or an analog thereof, X2 is P or an analog thereof, and X3 is Y or W or an analog thereof.

[0043] The homologues can be made by site-directed mutagenesis based on, e.g., a late domain motif-containing Rous sarcoma virus p2b peptide or another late domain-containing viral protein, or on a late domain motif-containing sequence of a protein in Table 1. The site-directed mutagenesis can be designed to generate amino acid substitutions, insertions, or deletions. Methods for conducting such mutagenesis should be apparent to skilled artisans in the field of molecular biology. The resultant homologues can be tested for their binding affinity to a type I WW-domain of Nedd4 or of a Nedd4-like protein.

[0044] The peptide portion in the compounds according to the present invention can also be in a modified form. Various modifications may be made to improve the stability and solubility of the compound, and/or optimize its binding affinity to a type I WW-domain of Nedd4. Examples of modified forms include, but are not limited to, glycosylated forms, phosphorylated forms, myristoylated forms, palmitoylated forms, ribosylated forms, acetylated forms, etc. Modifications also include intra-molecular crosslinking and covalent attachment to various moieties such as lipids, flavin, biotin, polyethylene glycol or derivatives thereof, etc. In addition, modifications may also include cyclization, and branching. Amino acids other than the conventional twenty amino acids encoded by genes may also be included in a polypeptide sequence in the compound of the present invention. For example, the compounds may include D-amino acids in place of L-amino acids.

[0045] To increase the stability of the compounds according to the present invention, various protection groups can also be incorporated into the amino acid residues of the compounds. In particular, terminal residues are preferably protected. Carboxyl groups may be protected by esters (e.g., methyl, ethyl, benzyl, p-nitrobenzyl, t-butyl or t-amyl esters, etc.), lower alkoxyl groups (e.g., methoxy, ethoxy, propoxy, butoxy, etc.), aralkyloxy groups (e.g., benzyloxy, etc.), amino groups, lower alkylamino or di(lower alkyl)amino groups. The term “lower alkoxy” is intended to mean an alkoxy group having a straight, branched or cyclic hydrocarbon moiety of up to six carbon atoms. Protection groups for amino groups may include lower alkyl, benzyloxycarbonyl, t-butoxycarbonyl, and sobornyloxycarbonyl. “Lower alkyl” is intended to mean an alkyl group having a straight, branched or cyclic hydrocarbon moiety of up to six carbon atoms. In one example, a 5-oxo-L-prolyl residue may be used in place of a prolyl residue. A 5-oxo-L-prolyl residue is especially desirable at the N-terminus of a peptide compound. In another example, when a proline residue is at the C-terminus of a peptide compound, a N-ethyl-L-prolinamide residue may be desirable in place of the proline residue. Various other protection groups known in the art useful in increasing the stability of peptide compounds can also be employed.

[0046] In addition, the compounds according to the present invention can also be in various pharmaceutically acceptable salt forms. “Pharmaceutically acceptable salts” refers to the relatively non-toxic, organic or inorganic salts of the compounds of the present invention, including inorganic or organic acid addition salts of the compound. Examples of such salts include, but are not limited to, hydrochloride salts, hydrobromide salts, sulfate salts, bisulfate salts, nitrate salts, acetate salts, phosphate salts, nitrate salts, oxalate salts, valerate salts, oleate salts, borate salts, benzoate salts, laurate saltes, stearate salts, palmitate salts, lactate salts, tosylate salts, citrate salts, maleate, salts, succinate salts, tartrate salts, naththylate salts, fumarate salts, mesylate salts, laurylsuphonate salts, glucoheptonate salts, and the like. See, e.g., Berge, et al. J. Pharm. Sci., 66:1-19 (1977).

[0047] Suitable pharmaceutically acceptable salts also include, but are not limited to, alkali metal salts, alkaline earth salts, and ammonium salts. Thus, suitable salts may be salts of aluminum, calcium, lithium, magnesium, potassium, sodium and zinc. In addition, organic salts may also be used including, e.g., salts of lysine, N,N′-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylglucamine), procaine and tris. In addition, metal complex forms (e.g. copper complex compounds, zinc complex compounds, etc.) of the compounds of the present invention may also exhibit improved stability.

[0048] Additionally, as will be apparent to skilled artisans apprised of the present disclosure, peptide mimetics can be designed based on the above-described compounds according to the present invention. However, it is noted that the mimetics preferably are capable of binding a type I WW-domain of Nedd4 or a Nedd4-like protein. For example, peptoid analogs of the PPPY motif can be prepared using known methods. Peptoids are oligomeric N-substituted glycines. Typically, various side chain groups can be included when forming an N-substituted glycine (peptoid monomer) that mimics a particular amino acid. Peptoid monomers can be linked together to form an oligomeric N-substituted glycines-peptoid. Peptoids are easy to synthesize in large amounts. In contrast to peptides, the backbone linkage of peptoids are resistant to hydrolytic enzymes. In addition, since a variety of functional groups can be presented as side chains off of the oligomeric backbone, peptoid analogs corresponding to any peptides can be produced with improved characterics. See Simon et al., Proc. Natl. Acad. Sci. USA, 89:9367-9371 (1992); Figliozzi et al., Methods Enzymol., 267:437-447 (1996); Horwell, Trends Biotechnol., 13:132-134 (1995); and Horwell, Drug Des. Discov., 12:63-75 (1994), all of which are incorporated herein by reference.

[0049] Thus, peptoid analogs of the above-described compounds of the present invention can be made using methods known in the art. The thus prepared peptoid analogs can be tested for their binding affinity to a type I WW-domain of Nedd4. They can also be tested in antiviral assays for their ability to inhibit viral budding from infected host cells and ability to inhibit viral propagation.

[0050] Mimetics of the compounds of the present invention can also be selected by rational drug design and/or virtual screening. Methods known in the art for rational drug design can be used in the present invention. See, e.g., Hodgson et al., Bio/Technology, 9:19-21 (1991); U.S. Pat. Nos. 5,800,998 and 5,891,628, all of which are incorporated herein by reference. An example of rational drug design is the development of HIV protease inhibitors. See Erickson et al., Science, 249:527-533 (1990). Structural information on a type I WW-domain of Nedd4 in complex with a PY motif-containing EnaC peptide is disclosed in Kanelis et al., Nat. Struct. Biol., 8:407-412 (2001), which is incorporated herein by reference. Structural information on the binding complex formed by the Nedd4 WW domain and the PPPY motif in a protein in Table 1 can also be obtained. The interacting complex can be studied using various biophysics techniques including, e.g., X-ray crystallography, NMR, computer modeling, mass spectrometry, and the like. Likewise, structural information can also be obtained from protein complexes formed by the Nedd4 WW domain and a variation of the PPPY motif.

[0051] Computer programs are employed to select compounds based on structural models. In addition, once an effective compound is identified, structural analogs or mimetics thereof can be produced based on rational drug design with the aim of improving drug efficacy and stability, and reducing side effects.

[0052] In addition, understanding of the interaction between a type I WW-domain of Nedd4 and compounds of the present invention can also be derived from mutagenesis analysis using yeast two-hybrid system or other methods for detection protein-protein interaction. In this respect, various mutations can be introduced into the interacting proteins and the effect of the mutations on protein-protein interaction is examined by a suitable method such as in vitro binding assay or the yeast two-hybrid system.

[0053] Various mutations including amino acid substitutions, deletions and insertions can be introduced into the protein sequence of a type I Nedd4 WW domain and/or a compound of the present invention using conventional recombinant DNA technologies. Generally, it is particularly desirable to decipher the protein binding sites. Thus, it is important that the mutations introduced only affect protein-protein interaction and cause minimal structural disturbances. Mutations are preferably designed based on knowledge of the three-dimensional structure of the interacting proteins. Preferably, mutations are introduced to alter charged amino acids or hydrophobic amino acids exposed on the surface of the proteins, since ionic interactions and hydrophobic interactions are often involved in protein-protein interactions. Alternatively, the “alanine scanning mutagenesis” technique is used. See Wells, et al., Methods Enzymol., 202:301-306 (1991); Bass et al., Proc. Natl. Acad. Sci. USA, 88:4498-4502 (1991); Bennet et al., J. Biol. Chem., 266:5191-5201 (1991); Diamond et al., J. Virol., 68:863-876 (1994). Using this technique, charged or hydrophobic amino acid residues of the interacting proteins are replaced by alanine, and the effect on the interaction between the proteins is analyzed using e.g., an in vitro binding assay. In this manner, the domains or residues of the proteins important to compound-target interaction can be identified.

[0054] Based on the structural information obtained, structural relationships between a type I Nedd4 WW domain and a compound of the present invention are elucidated. The moieties and the three-dimensional structures critical to the interaction are revealed. Medicinal chemists can then design analog compounds having similar moieties and structures.

[0055] The residues or domains critical to the modulating effect of the identified compound constitute the active region of the compound known as its “pharmacophore.”Once the pharmacophore has been elucidated, a structural model can be established by a modeling process that may incorporate data from NMR analysis, X-ray diffraction data, alanine scanning, spectroscopic techniques and the like. Various techniques including computational analysis, similarity mapping and the like can all be used in this modeling process. See e.g., Perry et al., in OSAR: Quantitative Structure-Activity Relationships in Drug Design, pp. 189-193, Alan R. Liss, Inc., 1989; Rotivinen et al., Acta Pharmaceutical Fennica, 97:159-166 (1988); Lewis et al., Proc. R. Soc. Lond., 236:125-140 (1989); McKinaly et al., Annu. Rev. Pharmacol. Toxiciol., 29:111-122 (1989). Commercial molecular modeling systems available from Polygen Corporation, Waltham, Mass., include the CHARMm program, which performs the energy minimization and molecular dynamics functions, and QUANTA program which performs the construction, graphic modeling and analysis of molecular structure. Such programs allow interactive construction, visualization and modification of molecules. Other computer modeling programs are also available from BioDesign, Inc. (Pasadena, Calif.), Hypercube, Inc. (Cambridge, Ontario), and Allelix, Inc. (Mississauga, Ontario, Canada).

[0056] A template can be formed based on the established model. Various compounds can then be designed by linking various chemical groups or moieties to the template. Various moieties of the template can also be replaced. These rationally designed compounds are further tested. In this manner, pharmacologically acceptable and stable compounds with improved efficacy and reduced side effect can be developed. The compounds identified in accordance with the present invention can be incorporated into a pharmaceutical formulation suitable for administration to an individual.

[0057] The mimetics including peptoid analogs can exhibit optimal binding affinity to a type I WW domain of human Nedd4 or animal orthologs thereof. Various known methods can be utilized to test the Nedd4-binding characteristics of a mimetics. For example, the entire Nedd4 protein or a fragment thereof containing a type I WW domain may be recombinantly expressed, purified, and contacted with the mimetics to be tested. Binding can be determined using a surface plasmon resonance biosensor. See e.g., Panayotou et al., Mol. Cell. Biol., 13:3567-3576 (1993). Other methods known in the art for estimating and determining binding constants in protein-protein interactions can also be employed. See Phizicky and Fields, et al., Microbiol. Rev., 59:94-123 (1995). For example, protein affinity chromatography may be used. First, columns are prepared with different concentrations of an interacting member, which is covalently bound to the columns. Then a preparation of its interacting partner is run through the column and washed with buffer. The interacting partner bound to the interacting member linked to the column is then eluted. Binding constant is then estimated based on the concentrations of the bound protein and the eluted protein. Alternatively, the method of sedimentation through gradients monitors the rate of sedimentation of a mixture of proteins through gradients of glycerol or sucrose. At concentrations above the binding constant, the two interacting members sediment as a complex. Thus, binding constant can be calculated based on the concentrations. Other suitable methods known in the art for estimating binding constant include but are not limited to gel filtration column such as nonequilibrium “small-zone” gel filtration columns (See e.g., Gill et al., J. Mol. Biol., 220:307-324 (1991)), the Hummel-Dreyer method of equilibrium gel filtration (See e.g., Hummel and Dreyer, Biochim. Biophys. Acta, 63:530-532 (1962)) and large-zone equilibrium gel filtration (See e.g., Gilbert and Kellett, J. Biol. Chem., 246:6079-6086 (1971)), sedimentation equilibrium (See e.g., Rivas and Minton, Trends Biochem., 18:284-287 (1993)), fluorescence methods such as fluorescence spectrum (See e.g., Otto-Bruc et al, Biochemistry, 32:8632-8645 (1993)) and fluorescence polarization or anisotropy with tagged molecules (See e.g., Weiel and Hershey, Biochemistry, 20:5859-5865 (1981)), and solution equilibrium measured with immobilized binding protein (See e.g., Nelson and Long, Biochemistry, 30:2384-2390 (1991)).

[0058] The compounds according the present invention can be delivered into cells by direct cell internalization, receptor mediated endocytosis, or via a “transporter.” It is noted that the compound administered to cells in vitro or in vivo in the method of the present invention preferably is delivered into the cells in order to achieve optimal results. Thus, preferably, the compound to be delivered is associated with a transporter capable of increasing the uptake of the compound by a mammalian cell, preferably a human cell, susceptible to infection by a virus, particularly a virus selected from those in Table 1. As used herein, the term “associated with” means a compound to be delivered is physically associated with a transporter. The compound and the transporter can be covalently linked together, or associated with each other as a result of physical affinities such as forces caused by electrical charge differences, hydrophobicity, hydrogen bonds, van der Waals force, ionic force, or a combination thereof. For example, the compound can be encapsulated within a transporter such as a cationic liposome.

[0059] As used herein, the term “transporter” refers to an entity (e.g., a compound or a composition or a physical structure formed from multiple copies of a compound or multiple different compounds) that is capable of facilitating the uptake of a compound of the present invention by a mammalian cell, particularly a human cell. Typically, the cell uptake of a compound of the present invention in the presence of a “transporter” is at least 50% higher than the cell uptake of the compound in the absence of the “transporter.” Preferably, the cell uptake of a compound of the present invention in the presence of a “transporter” is at least 75% higher, preferably at least 100% or 200% higher, and more preferably at least 300%, 400% or 500% higher than the cell uptake of the compound in the absence of the “transporter.” Methods of assaying cell uptake of a compound should be apparent to skilled artisans. For example, the compound to be delivered can be labeled with a radioactive isotope or another detectable marker (e.g., a fluorescence marker), and added to cultured cells in the presence or absence of a transporter, and incubated for a time period sufficient to allow maximal uptake. Cells can then be separated from the culture medium and the detectable signal (e.g., radioactivity) caused by the compound inside the cells can be measured. The result obtained in the presence of a transporter can be compared to that obtained in the absence of a transporter.

[0060] Many molecules and structures known in the art can be used as “transporter.” In one embodiment, a penetratin is used as a transporter. For example, the homeodomain of Antennapedia, a Drosophila transcription factor, can be used as a transporter to deliver a compound of the present invention. Indeed, any suitable member of the penetratin class of peptides can be used to carry a compound of the present invention into cells. Penetratins are disclosed in, e.g., Derossi et al., Trends Cell Biol., 8:84-87 (1998), which is incorporated herein by reference. Penetratins transport molecules attached thereto across cytoplasm membranes or nucleus membranes efficiently in a receptor-independent, energy-independent, and cell type-independent manner. Methods for using a penetratin as a carrier to deliver oligonucleotides and polypeptides are also disclosed in U.S. Pat. No. 6,080,724; Pooga et al., Nat. Biotech., 16:857 (1998); and Schutze et al., J. Immunol., 157:650 (1996), all of which are incorporated herein by reference. U.S. Pat. No. 6,080,724 defines the minimal requirements for a penetratin peptide as a peptide of 16 amino acids with 6 to 10 of which being hydrophobic. The amino acid at position 6 counting from either the N- or C-terminal is tryptophan, while the amino acids at positions 3 and 5 counting from either the N- or C-terminal are not both valine. Preferably, the helix 3 of the homeodomain of Drosophila Antennapedia is used as a transporter. More preferably, a peptide having a sequence of the amino acids 43-58 of the homeodomain Antp is employed as a transporter. In addition, other naturally occurring homologs of the helix 3 of the homeodomain of Drosophila Antennapedia can also be used. For example, homeodomains of Fushi-tarazu and Engrailed have been shown to be capable of transporting peptides into cells. See Han et al., Mol. Cells, 10:728-32 (2000). As used herein, the term “penetratin” also encompasses peptoid analogs of the penetratin peptides. Typically, the penetratin peptides and peptoid analogs thereof are covalently linked to a compound to be delivered into cells thus increasing the cellular uptake of the compound.

[0061] In another embodiment, the HIV-1 tat protein or a derivative thereof is used as a “transporter” covalently linked to a compound according to the present invention. The use of HIV-1 tat protein and derivatives thereof to deliver macromolecules into cells has been known in the art. See Green and Loewenstein, Cell, 55:1179 (1988); Frankel and Pabo, Cell, 55:1189 (1988); Vives et al., J. Biol. Chem., 272:16010-16017 (1997); Schwarze et al., Science, 285:1569-1572 (1999). It is known that the sequence responsible for cellular uptake consists of the highly basic region, amino acid residues 49-57. See e.g., Vives et al., J. Biol. Chem., 272:16010-16017 (1997); Wender et al., Proc. Nat'l Acad. Sci. USA, 97:13003-13008 (2000). The basic domain is believed to target the lipid bilayer component of cell membranes. It causes a covalently linked protein or nucleic acid to cross cell membrane rapidly in a cell type-independent manner. Proteins ranging in size from 15 to 120 kD have been delivered with this technology into a variety of cell types both in vitro and in vivo. See Schwarze et al., Science, 285:1569-1572 (1999). Any HIV tat-derived peptides or peptoid analogs thereof capable of transporting macromolecules such as peptides can be used for purposes of the present invention. For example, any native tat peptides having the highly basic region, amino acid residues 49-57 can be used as a transporter by covalently linking it to the compound to be delivered. In addition, various analogs of the tat peptide of amino acid residues 49-57 can also be useful transporters for purposes of this invention. Examples of various such analogs are disclosed in Wender et al., Proc. Nat'l. Acad. Sci. USA, 97:13003-13008 (2000) (which is incorporated herein by reference) including, e.g., d-Tat49-57, retro-inverso isomers of l- or d-Tat49-57 (i.e., l-Tat57-49 and d-Tat57-49), L-arginine oligomers, D-arginine oligomers, L-lysine oligomers, D-lysine oligomers, L-histine oligomers, D-histine oligomers, L-ornithine oligomers, D-ornithine oligomers, and various homologues, derivatives (e.g., modified forms with conjugates linked to the small peptides) and peptoid analogs thereof. Typically, arginine oligomers are preferred to the other oligomers, arginine oligomers are much more efficient in promoting cellular uptake. As used herein, the term “oligomer” means a molecule that includes a covalently linked chain of amino acid residues of the same amino acids having a large enough number of such amino acid residues to confer transporter activities on the molecule. Typically, an oligomer contains at least 6, preferably at least 7, 8, or at least 9 such amino acid residues. In one embodiment, the transporter is a peptide that includes at least six contiguous amino acid residues that are a combination of two or more of L-arginine, D-arginine, L-lysine, D-lysine, L-histidine, D-histine, L-ornithine, and D-ornithine.

[0062] Other useful transporters known in the art include, but are not limited to, short peptide sequences derived from fibroblast growth factor (See Lin et al., J. Biol. Chem., 270:14255-14258 (1998)), Galparan (See Pooga et al., FASEB J. 12:67-77 (1998)), and HSV-1 structural protein VP22 (See Elliott and O'Hare, Cell, 88:223-233 (1997)).

[0063] In addition to peptide-based transporters, various other types of transporters can also be used, including but not limited to cationic liposomes (see Rui et al., J. Am. Chem. Soc., 120:11213-11218 (1998)), dendrimers (Kono et al., Bioconjugate Chem., 10:1115-1121 (1999)), siderophores (Ghosh et al., Chem. Biol., 3:1011-1019 (1996)), etc. In a specific embodiment, the compound according to the present invention is encapsulated into liposomes for delivery into cells.

[0064] Additionally, when a compound according to the present invention is a peptide, it can be introduced into cells by a gene therapy method. That is, a nucleic acid encoding the peptide can be administered to in vitro cells or to cells in vivo in a human or animal body. The nucleic acid encoding the peptide may or may not also encode a peptidic transporter as described above. Various gene therapy methods are well known in the art. Successes in gene therapy have been reported recently. See e.g., Kay et al., Nature Genet., 24:257-61 (2000); Cavazzana-Calvo et al., Science, 288:669 (2000); and Blaese et al., Science, 270: 475 (1995); Kantoff, et al., J. Exp. Med., 166:219 (1987).

[0065] In one embodiment, the peptide consists of a contiguous amino acid sequence of from 8 to about 30 amino acid residues of a viral protein selected from the group consisting of hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, and TT virus ORF2 protein, wherein the contiguous amino acid sequence encompasses the PPXY motif of the viral protein, and wherein the peptide is capable of binding a type I WW-domain of the Nedd4 protein. Preferably, the peptide consists of at least 9, 10, 11, 12, 13, 14, or 15 amino acids. Also preferably, the peptide consists of no greater than 25, 24, 23, 22, 21, 20, 19, 18, 17, 16 or 15 amino acids. More preferably, the peptide consists of from 9 to 20, 23 or 25 amino acids, or from 10 or 11 to 20, 23 or 25 amino acids.

[0066] For example, the peptide can include an amino acid sequence selected from the group consisting of SEQ ID NOs:24-36, SEQ ID NOs:154-295, SEQ ID NOs:296-438, SEQ ID NOs:439-581, SEQ ID NOs:582-724, SEQ ID NOs:725-1010, SEQ ID NOs:1011-1296, SEQ ID NOs:1297-1439, SEQ ID NOs:1440-1452, SEQ ID NOs:1453-1491, SEQ ID NOs:1492-1530, and SEQ ID NOs:1531-1673.

[0067] Any suitable gene therapy methods may be used for purposes of the present invention. Generally, an exogenous nucleic acid encoding a peptide compound of the present invention is incorporated into a suitable expression vector and is operably linked to a promoter in the vector. Suitable promoters include but are not limited to viral transcription promoters derived from adenovirus, simian virus 40 (SV40) (e.g., the early and late promoters of SV40), Rous sarcoma virus (RSV), and cytomegalovirus (CMV) (e.g., CMV immediate-early promoter), human immunodeficiency virus (HIV) (e.g., long terminal repeat (LTR)), vaccinia virus (e.g., 7.5K promoter), and herpes simplex virus (HSV) (e.g., thymidine kinase promoter). Where tissue-specific expression of the exogenous gene is desirable, tissue-specific promoters may be operably linked to the exogenous gene. In addition, selection markers may also be included in the vector for purposes of selecting, in vitro, those cells that contain the exogenous nucleic acid encoding the peptide compound of the present invention. Various selection markers known in the art may be used including, but not limited to, e.g., genes conferring resistance to neomycin, hygromycin, zeocin, and the like.

[0068] In one embodiment, the exogenous nucleic acid is incorporated into a plasmid DNA vector. Many commercially available expression vectors may be useful for the present invention, including, e.g., pCEP4, pcDNAI, pIND, pSecTag2, pVAX1, pcDNA3.1, and pBI-EGFP, and pDisplay.

[0069] Various viral vectors may also be used. Typically, in a viral vector, the viral genome is engineered to eliminate the disease-causing capability, e.g., the ability to replicate in the host cells. The exogenous nucleic acid to be introduced into a patient may be incorporated into the engineered viral genome, e.g., by inserting it into a viral gene that is non-essential to the viral infectivity. Viral vectors are convenient to use as they can be easily introduced into tissue cells by way of infection. Once in the host cell, the recombinant virus typically is integrated into the genome of the host cell. In rare instances, the recombinant virus may also replicate and remain as extrachromosomal elements.

[0070] A large number of retroviral vectors have been developed for gene therapy. These include vectors derived from oncoretroviruses (e.g., MLV), viruses (e.g., HIV and SIV) and other retroviruses. For example, gene therapy vectors have been developed based on murine leukemia virus (See, Cepko, et al., Cell, 37:1053-1062 (1984), Cone and Mulligan, Proc. Natl. Acad. Sci. U.S.A., 81:6349-6353 (1984)), mouse mammary tumor virus (See, Salmons et al., Biochem. Biophys. Res. Commun., 159:1191-1198 (1984)), gibbon ape leukemia virus (See, Miller et al., J. Virology, 65:2220-2224 (1991)), HIV, (See Shimada et al., J. Clin. Invest., 88:1043-1047 (1991)), and avian retroviruses (See Cosset et al., J. Virology, 64:1070-1078 (1990)). In addition, various retroviral vectors are also described in U.S. Pat. Nos. 6,168,916; 6,140,111; 6,096,534; 5,985,655; 5,911,983; 4,980,286; and 4,868,116, all of which are incorporated herein by reference.

[0071] Adeno-associated virus (AAV) vectors have been successfully tested in clinical trials. See e.g., Kay et al., Nature Genet. 24:257-61 (2000). AAV is a naturally occurring defective virus that requires other viruses such as adenoviruses or herpes viruses as helper viruses. See Muzyczka, Curr. Top. Microbiol. Immun., 158:97 (1992). A recombinant AAV virus useful as a gene therapy vector is disclosed in U.S. Pat. No. 6,153,436, which is incorporated herein by reference.

[0072] Adenoviral vectors can also be useful for purposes of gene therapy in accordance with the present invention. For example, U.S. Pat. No. 6,001,816 discloses an adenoviral vector, which is used to deliver a leptin gene intravenously to a mammal to treat obesity. Other recombinant adenoviral vectors may also be used, which include those disclosed in U.S. Pat. Nos. 6,171,855; 6,140,087; 6,063,622; 6,033,908; and 5,932,210, and Rosenfeld et al., Science, 252:431-434 (1991); and Rosenfeld et al., Cell, 68:143-155 (1992).

[0073] Other useful viral vectors include recombinant hepatitis viral vectors (See, e.g., U.S. Pat. No. 5,981,274), and recombinant entomopox vectors (See, e.g., U.S. Pat. Nos. 5,721,352 and 5,753,258).

[0074] Other non-traditional vectors may also be used for purposes of this invention. For example, International Publication No. WO 94/18834 discloses a method of delivering DNA into mammalian cells by conjugating the DNA to be delivered with a polyelectrolyte to form a complex. The complex may be microinjected into or taken up by cells.

[0075] The exogenous nucleic acid fragment or plasmid DNA vector containing the exogenous gene may also be introduced into cells by way of receptor-mediated endocytosis. See e.g., U.S. Pat. No. 6,090,619; Wu and Wu, J. Biol. Chem., 263:14621 (1988); Curiel et al., Proc. Natl. Acad. Sci. USA, 88:8850 (1991). For example, U.S. Pat. No. 6,083,741 discloses introducing an exogenous nucleic acid into mammalian cells by associating the nucleic acid to a polycation moiety (e.g., poly-L-lysine, having 3-100 lysine residues), which is itself coupled to an integrin receptor binding moiety (e.g., a cyclic peptide having the amino acid sequence RGD).

[0076] Alternatively, the exogenous nucleic acid or vectors containing it can also be delivered into cells via amphiphiles. See e.g., U.S. Pat. No. 6,071,890. Typically, the exogenous nucleic acid or a vector containing the nucleic acid forms a complex with the cationic amphiphile. Mammalian cells contacted with the complex can readily absorb the complex.

[0077] The exogenous nucleic acid can be introduced into a patient for purposes of gene therapy by various methods known in the art. For example, the exogenous nucleic acid alone or in a conjugated or complex form described above, or incorporated into viral or DNA vectors, may be administered directly by injection into an appropriate tissue or organ of a patient. Alternatively, catheters or like devices may be used for delivery into a target organ or tissue. Suitable catheters are disclosed in, e.g., U.S. Pat. Nos. 4,186,745; 5,397,307; 5,547,472; 5,674,192; and 6,129,705, all of which are incorporated herein by reference.

[0078] In addition, the exogenous nucleic acid encoding a peptide compound of the present invention or vectors containing the nucleic acid can be introduced into isolated cells using any known techniques such as calcium phosphate precipitation, microinjection, lipofection, electroporation, gene gun, receptor-mediated endocytosis, and the like. Cells expressing the exogenous gene may be selected and redelivered back to the patient by, e.g., injection or cell transplantation. The appropriate amount of cells delivered to a patient will vary with patient conditions, and desired effect, which can be determined by a skilled artisan. See e.g., U.S. Pat. Nos. 6,054,288; 6,048,524; and 6,048,729. Preferably, the cells used are autologous, i.e., obtained from the patient being treated.

[0079] When the transporter used in the method of the present invention is a peptidic transporter, a hybrid polypeptide or fusion polypeptide is provided. In preferred embodiments, the hybrid polypeptide includes (a) a first portion comprising an amino acid sequence motif PPXY, and capable of binding a type I WW-domain of Nedd4, wherein X is an amino acid, preferably is proline, alanine, glutamic acid, asparagine or arginine, and (b) a second portion which is a peptidic transporter capable of increasing the uptake of the first portion by a human cell.

[0080] In one embodiment, the hybrid polypeptide includes from about 8 to about 100 amino acid residues, preferably 9 to 50 amino acid residues, more preferably 12 to 30 amino acid residues, and even more preferably from about 14 to 20 amino acid residues.

[0081] In a specific embodiment, the hybrid polypeptide does not contain a terminal L-histidine oligomer. As used herein, the term “terminal L-histidine oligomer” means an L-histidine oligomer at either of the two termini of the hybrid polypeptide, or at no more than one, two or three amino acid residues from either terminus of the hybrid polypeptide.

[0082] Preferably, the peptidic transporter is capable of increasing the uptake of the first portion by a mammalian cell by at least 100%, more preferably by at least 300%, 400% or 500%. In one embodiment, the first portion does not contain a contiguous amino acid sequence of a matrix protein of Ebola virus that is sufficient to impart an ability to bind the UEV domain of Tsg101 on the portion.

[0083] The hybrid polypeptide can be produced in a patient's body by administering to the patient a nucleic acid encoding the hybrid polypeptide by a gene therapy method as described above. Alternatively, the hybrid polypeptide can be chemically synthesized or produced by recombinant expression.

[0084] Thus, the present invention also provides isolated nucleic acids encoding the hybrid polypeptides and host cells containing the nucleic acid and recombinantly expressing the hybrid polypeptides. Such a host cell can be prepared by introducing into a suitable cell an exogenous nucleic acid encoding one of the hybrid polypeptides by standard molecular cloning techniques as described above. The nucleic acids can be prepared by linking a nucleic acid encoding the first portion and a nucleic acid encoding the second portion. Methods for preparing such nucleic acids and for using them in recombinant expression should be apparent to skilled artisans.

[0085] The compounds according to the present invention are a novel class of anti-viral compounds distinct from other commercially available compounds. While not wishing to be bound by any theory or hypothesis, it is believed that the compounds according to the present invention inhibit virus through a mechanism distinct from those of the anti-viral compounds known in the art. Therefore, it may be desirable to employ combination therapies to administer to a patient both a compound according to the present invention, with or without a transporter, and another anti-viral compound of a different class. However, it is to be understood that such other anti-viral compounds should be pharmaceutically compatible with the compound of the present invention. By “pharmaceutically compatible” it is intended that the other anti-viral agent(s) will not interact or react with the above composition, directly or indirectly, in such a way as to adversely affect the effect of the treatment, or to cause any significant adverse side reaction in the patient. In this combination therapy approach, the two different pharmaceutically active compounds can be administered separately or in the same pharmaceutical composition. Compounds suitable for use in combination therapies with the compounds according to the present invention include, but are not limited to, small molecule drugs, antibodies, immunomodulators, and vaccines.

[0086] Typically, a compound of the present invention is administered to a patient in a pharmaceutical composition, which typically includes one or more pharmaceutically acceptable carriers that are inherently nontoxic and non-therapeutic. That is, the compounds are used in the manufacture of medicaments for use in the methods of treating viral infection provided in the present invention.

[0087] The pharmaceutical composition according to the present invention may be administered to a subject needing treatment or prevention through any appropriate routes such as parenteral, oral, or topical administration. The active compounds of this invention are administered at a therapeutically effective amount to achieve the desired therapeutic effect without causing any serious adverse effects in the patient treated. Generally, the toxicity profile and therapeutic efficacy of therapeutic agents can be determined by standard pharmaceutical procedures in suitable cell models or animal models or human clinical trials. As is known in the art, the LD50 represents the dose lethal to about 50% of a tested population. The ED50 is a parameter indicating the dose therapeutically effective in about 50% of a tested population. Both LD50 and ED50 can be determined in cell models and animal models. In addition, the IC50 may also be obtained in cell models and animal models, which stands for the circulating plasma concentration that is effective in achieving about 50% of the maximal inhibition of the symptoms of a disease or disorder. Such data may be used in designing a dosage range for clinical trials in humans. Typically, as will be apparent to skilled artisans, the dosage range for human use should be designed such that the range centers around the ED50 and/or IC50, but significantly below the LD50 obtained from cell or animal models.

[0088] Typically, the compounds of the present invention can be effective at an amount of from about 0.01 microgram to about 5000 mg per day, preferably from about 1 microgram to about 2500 mg per day. However, the amount can vary with the body weight of the patient treated and the state of disease conditions. The active ingredient may be administered at once, or may be divided into a number of smaller doses to be administered at predetermined intervals of time. The suitable dosage unit for each administration of the compounds of the present invention can be, e.g., from about 0.01 microgram to about 2000 mg, preferably from about 1 microgram to about 1000 mg.

[0089] In the case of combination therapy, a therapeutically effective amount of another anti-viral compound can be administered in a separate pharmaceutical composition, or alternatively included in the pharmaceutical composition that contains a compound according to the present invention. The pharmacology and toxicology of many of such other anti-viral compounds are known in the art. See e.g., Physicians Desk Reference, Medical Economics, Montvale, N.J.; and The Merck Index, Merck & Co., Rahway, N.J. The therapeutically effective amounts and suitable unit dosage ranges of such compounds used in art can be equally applicable in the present invention.

[0090] It should be understood that the dosage ranges set forth above are exemplary only and are not intended to limit the scope of this invention. The therapeutically effective amount for each active compound can vary with factors including but not limited to the activity of the compound used, stability of the active compound in the patient's body, the severity of the conditions to be alleviated, the total weight of the patient treated, the route of administration, the ease of absorption, distribution, and excretion of the active compound by the body, the age and sensitivity of the patient to be treated, and the like, as will be apparent to a skilled artisan. The amount of administration can also be adjusted as the various factors change over time.

[0091] The active compounds according to this invention can be administered to patients to be treated through any suitable routes of administration. Advantageously, the active compounds are delivered to the patient parenterally, i.e., by intravenous, intramuscular, intraperiotoneal, intracisternal, subcutaneous, or intraarticular injection or infusion.

[0092] For parenteral administration, the active compounds can be formulated into solutions or suspensions, or in lyophilized forms for conversion into solutions or suspensions before use. Lyophilized compositions may include pharmaceutically acceptable carriers such as gelatin, DL-lactic and glycolic acids copolymer, D-mannitol, etc. To convert the lyophilized forms into solutions or suspensions, diluent containing, e.g., carboxymethylcellulose sodium, D-mannitol, polysorbate 80, and water may be employed. Lyophilized forms may be stored in, e.g., a dual chamber syringe with one chamber containing the lyophilized composition and the other chamber containing the diluent. In addition, the active ingredient(s) can also be incorporated into sterile lyophilized microspheres for sustained release. Methods for making such microspheres are generally known in the art. See U.S. Pat. Nos. 4,652,441; 4,728,721; 4,849,228; 4,917,893; 4,954,298; 5,330,767; 5,476,663; 5,480,656; 5,575,987; 5,631,020; 5,631,021; 5,643,607; and 5,716,640.

[0093] In a solution or suspension form suitable for parenteral administration, the pharmaceutical composition can include, in addition to a therapeutically or prophylactically effective amount of a compound of the present invention, a buffering agent, an isotonicity adjusting agent, a preservative, and/or an anti-absorbent. Examples of suitable buffering agent include, but are not limited to, citrate, phosphate, tartrate, succinate, adipate, maleate, lactate and acetate buffers, sodium bicarbonate, and sodium carbonate, or a mixture thereof. Preferably, the buffering agent adjusts the pH of the solution to within the range of 5-8. Examples of suitable isotonicity adjusting agents include sodium chloride, glycerol, mannitol, and sorbitol, or a mixture thereof. A preservative (e.g., anti-microbial agent) may be desirable as it can inhibit microbial contamination or growth in the liquid forms of the pharmaceutical composition. Useful preservatives may include benzyl alcohol, a paraben and phenol or a mixture thereof. Materials such as human serum albumin, gelatin or a mixture thereof may be used as anti-absorbents. In addition, conventional solvents, surfactants, stabilizers, pH balancing buffers, and antioxidants can all be used in the parenteral formulations, including but not limited to dextrose, fixed oils, glycerine, polyethylene glycol, propylene glycol, ascorbic acid, sodium bisulfite, and the like. The parenteral formulation can be stored in any conventional containers such as vials, ampoules, and syringes.

[0094] The active compounds can also be delivered orally in enclosed gelatin capsules or compressed tablets. Capsules and tablets can be prepared in any conventional techniques. For example, the active compounds can be incorporated into a formulation which includes pharmaceutically acceptable carriers such as excipients (e.g., starch, lactose), binders (e.g., gelatin, cellulose, gum tragacanth), disintegrating agents (e.g., alginate, Primogel, and corn starch), lubricants (e.g., magnesium stearate, silicon dioxide), and sweetening or flavoring agents (e.g., glucose, sucrose, saccharin, methyl salicylate, and peppermint). Various coatings can also be prepared for the capsules and tablets to modify the flavors, tastes, colors, and shapes of the capsules and tablets. In addition, liquid carriers such as fatty oil can also be included in capsules.

[0095] Other forms of oral formulations such as chewing gum, suspension, syrup, wafer, elixir, and the like can also be prepared containing the active compounds used in this invention. Various modifying agents for flavors, tastes, colors, and shapes of the special forms can also be included. In addition, for convenient administration by enteral feeding tube in patients unable to swallow, the active compounds can be dissolved in an acceptable lipophilic vegetable oil vehicle such as olive oil, corn oil and safflower oil.

[0096] The active compounds can also be administered topically through rectal, vaginal, nasal, bucal, or mucosal applications. Topical formulations are generally known in the art including creams, gels, ointments, lotions, powders, pastes, suspensions, sprays, drops and aerosols. Typically, topical formulations include one or more thickening agents, humectants, and/or emollients including but not limited to xanthan gum, petrolatum, beeswax, or polyethylene glycol, sorbitol, mineral oil, lanolin, squalene, and the like.

[0097] A special form of topical administration is delivery by a transdermal patch. Methods for preparing transdermal patches are disclosed, e.g., in Brown, et al., Annual Review of Medicine, 39:221-229 (1988), which is incorporated herein by reference.

[0098] The active compounds can also be delivered by subcutaneous implantation for sustained release. This may be accomplished by using aseptic techniques to surgically implant the active compounds in any suitable formulation into the subcutaneous space of the anterior abdominal wall. See, e.g., Wilson et al., J. Clin. Psych. 45:242-247 (1984). Sustained release can be achieved by incorporating the active ingredients into a special carrier such as a hydrogel. Typically, a hydrogel is a network of high molecular weight biocompatible polymers, which can swell in water to form a gel like material. Hydrogels are generally known in the art. For example, hydrogels made of polyethylene glycols, or collagen, or poly(glycolic-co-L-lactic acid) are suitable for this invention. See, e.g., Phillips et al., J. Pharmaceut. Sci., 73:1718-1720 (1984).

[0099] The active compounds can also be conjugated, i.e., covalently linked, to a water soluble non-immunogenic high molecular weight polymer to form a polymer conjugate. Preferably, such polymers do not undesirably interfere with the cellular uptake of the active compounds. Advantageously, such polymers, e.g., polyethylene glycol, can impart solubility, stability, and reduced immunogenicity to the active compounds. As a result, the active compound in the conjugate when administered to a patient, can have a longer half-life in the body, and exhibit better efficacy. In one embodiment, the polymer is a peptide such as albumin or antibody fragment Fc. PEGylated proteins are currently being used in protein replacement therapies and for other therapeutic uses. For example, PEGylated adenosine deaminase (ADAGEN®) is being used to treat severe combined immunodeficiency disease (SCIDS). PEGylated L-asparaginase (ONCAPSPAR®) is being used to treat acute lymphoblastic leukemia (ALL). A general review of PEG-protein conjugates with clinical efficacy can be found in, e.g., Burnham, Am. J. Hosp. Pharm., 15:210-218 (1994). Preferably, the covalent linkage between the polymer and the active compound is hydrolytically degradable and is susceptible to hydrolysis under physiological conditions. Such conjugates are known as “prodrugs” and the polymer in the conjugate can be readily cleaved off inside the body, releasing the free active compounds.

[0100] Alternatively, other forms controlled release or protection including microcapsules and nanocapsules generally known in the art, and hydrogels described above can all be utilized in oral, parenteral, topical, and subcutaneous administration of the active compounds.

[0101] Another preferable delivery form is using liposomes as carrier. Liposomes are micelles formed from various lipids such as cholesterol, phospholipids, fatty acids, and derivatives thereof. Active compounds can be enclosed within such micelles. Methods for preparing liposomal suspensions containing active ingredients therein are generally known in the art and are disclosed in, e.g., U.S. Pat. No. 4,522,811, and Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976), p. 33 et seq., both of which are incorporated herein by reference. Several anticancer drugs delivered in the form of liposomes are known in the art and are commercially available from Liposome Inc. of Princeton, N.J., U.S.A. It has been shown that liposomes can reduce the toxicity of the active compounds, and increase their stability.

EXAMPLE 1

[0102] Fragments of the viral proteins selected from those in Table 1 are tested from their interaction with human Nedd4 using yeast two-hybrid system. That is, to prepare a yeast two-hybrid activation domain-Nedd4 construct, a DNA fragment encompassing the full-length coding sequence for Nedd4 is obtained by PCR from a human fetal brain cDNA library and cloned into the EcoRI/Pst1 sites of the activation domain parent plasmid GADpN2 (LEU2, CEN4, ARS1, ADH1p-SV40NLS-GAL4 (768-881)-MCS (multiple cloning site)-PGK1t, AmpR, ColE1_ori). To prepare the yeast two-hybrid DNA binding domain-PPPY-containing viral peptide construct, a DNA fragment corresponding to a contiguous amino acid sequence of a viral protein in Table 1 that spans the PPPY motif therein is obtained and is cloned into the EcoRI/Sal1 sites of the binding domain parent plasmid pGBT.Q.

[0103] To perform the yeast two-hybrid assays, yeast cells of the strain Y189 purchased from Clontech (ura3-52 his3*200 ade2-101 trp1-901 leu2-3,112 met gal4 gal80 URA3::GAL1p-lacZ) are co-transformed with the activation domain-Nedd4 construct and a binding domain-PPPY-containing viral peptide construct or the binding domain-wild type RSV p2b construct. Filter lift assays for β-Gal activity are conducted by lifting the transformed yeast colonies with filters, lysing the yeast cells by freezing and thawing, and contacting the lysed cells with X-Gal. Positive β-Gal activity indicates that the p2b wild type or PPPY-containing viral peptide interacts with Nedd4. All binding domain constructs are also tested for self-activation of β-Gal activity.

EXAMPLE 2

[0104] A fusion protein with a GST tag fused to the RSV Gag p2b domain is recombinantly expressed and purified by chromatography. In addition, a series of fusion peptides containing a PPXY-containing short peptide according to the present invention fused to a peptidic transporter are synthesized chemically by standard peptide synthesis methods or recombinantly expressed in a standard protein expression system. The PPXY-containing short peptides are fused to a peptidic transporter such as the helix 3 of the homeodomain of Drosophila Antennapedia, HSV VP22, d-Tat49-57, retro-inverso isomers of l- or d-Tat49-57 (i.e., l-Tat57-49 and d-Tat57-49), L-arginine oligomers, and D-arginine oligomers. A number of PPXY-containing short peptides are also prepared by chemical synthesis or recombinant expression, e.g., free and unfused peptides having a sequence selected from the group of SEQ ID NOs:24-36. The peptides are purified by conventional protein purification techniques, e.g., by chromatography.

[0105] Nunc/Nalgene Maxisorp plates are incubated overnight at 4° C. or for 1-2 hrs at room temperature in 100 μl of a protein coupling solution containing purified GST-p6 and 50 mM Carbonate, pH=9.6. This allows the attachment of the GST-p6 fusion protein to the plates. Liquids in the plates are then emptied and wells filled with 400 μl/well of a blocking buffer (SuperBlock; Pierce-Endogen, Rockford, Ill.). After incubating for 1 hour at room temperature, 100 μl of a mixture containing Drosophila S2 cell lysate myc-tagged Nedd4 and a PPXY-containing short peptide is applied to the wells of the plate. This mixture is allowed to react for 2 hours at room temperature to form p2b:Nedd4 protein-protein complexes.

[0106] Plates are then washed 4×100 μl with 1×PBST solution (Invitrogen; Carlsbad, Calif.). After washing, 100 μl of 1 μg/ml solution of anti-myc monoclonal antibody (Clone 9E10; Roche Molecular Biochemicals; Indianapolis, Ind.) in 1×PBST is added to the wells of the plate to detect the myc-epitope tag on the Nedd4 protein. Plates are then washed again with 4×100 μl with 1×PBST solution and 100 μl of 1 μg/ml solution of horseradish peroxidase (HRP) conjugated Goat anti-mouse IgG (Jackson Immunoresearch Labs; West Grove, Pa.) in 1×PBST is added to the wells of the plate to detect bound mouse anti-myc antibodies. Plates are then washed again with 4×100 μl with 1×PBST solution and 100 μl of fluorescent substrate (QuantaBlu; Pierce-Endogen, Rockford, Ill.) is added to all wells. After 30 minutes, 100 μl of stop solution is added to each well to inhibit the function of HRP. Plates are then read on a Packard Fusion instrument at an excitation wavelength of 325 nm and an emission wavelength of 420 nm. The presence of fluorescent signals indicates binding of Nedd4 to the fixed GST-p2b. In contrast, the absence of fluorescent signals indicates that the PPXY-containing short peptide is capable of disrupting the interaction between Nedd4 and RSV p2b.

EXAMPLE 3

[0107] The following examples demonstrate the anti-viral effect of the PPXY-containing short peptides tested in Example 2. The assay used is similar to the assay described by Korba and Milman, Antiviral Res., 15:217-228 (1991) and Korba and Gerin, Antiviral Res., 19:55-70 (1992), with the exception that viral DNA detection and quantification is simplified. Briefly, HepG2-2.2.15 cells are plated in 96-well microtiter plates at an initial density of 2×104 cells/100 μl in DMEM medium supplemented with 10% fetal bovine serum. To promote cell adherence, the 96-well plates have been pre-coated with collagen prior to cell plating. After incubation at 37° C. in a humidified, 5% CO2 environment for 16-24 hours, the confluent monolayer of HepG2-2.2.15 cells is washed and the medium is replaced with complete medium containing various concentrations of test compound. Every three days, the culture medium is replaced with fresh medium containing the appropriately diluted drug. Nine days following the initial administration of test compounds, the cell culture supernate is collected and clarified by centrifugation (Sorvall RT-6000D centrifuge, 1000 rpm for 5 min). Three microliters of clarified supernate is then subjected to real-time quantitative PCR using conditions described below.

[0108] Virion-associated HBV DNA present in the tissue culture supernate is PCR amplified using primers derived from HBV strain ayw. Subsequently, the PCR-amplified HBV DNA is detected in real-time (i.e., at each PCR thermocycle step) by monitoring increases in fluorescence signals that result from exonucleolytic degradation of a quenched fluorescent probe molecule following hybridization of the probe to the amplified HBV DNA. The probe molecule, designed with the aid of Primer Express™ (PE-Applied Biosystems) software, is complementary to DNA sequences present in the HBV DNA region amplified.

[0109] Routinely, 3 μl of clarified supernate is analyzed directly (without DNA extraction) in a 50 μl PCR reaction. Reagents and conditions used are per the manufacturers suggestions (PE-Applied Biosystems). For each PCR amplification, a standard curve is simultaneously generated several log dilutions of a purified 1.2 kbp HBVayw subgenomic fragment; routinely, the standard curve ranged from 1×106 to 1×10 nominal copy equivalents per PCR reaction.

[0110] All publications and patent applications mentioned in the specification are indicative of the level of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

[0111] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims.

TABLE 2
PPXY Motif Containing Peptides from Ebola Virus
Matrix Protein
(GenBank Accession No. AAL25816)
PPEYMEAI             SEQ ID NO:39
PPEYMEAIY            SEQ ID NO:40
PPEYMEAIYP           SEQ ID NO:41
PPEYMEAIYPV          SEQ ID NO:42
PPEYMEAIYPVR         SEQ ID NO:43
PPEYMEAIYPVRS        SEQ ID NO:44
PPEYMEAIYPVRSN       SEQ ID NO:45
PPEYMEAIYPVRSNS      SEQ ID NO:46
PPEYMEAIYPVRSNST     SEQ ID NO:47
PPEYMEAIYPVRSNSTI    SEQ ID NO:48
PPEYMEAIYPVRSNSTIA   SEQ ID NO:49
PPEYMEAIYPVRSNSTIAR  SEQ ID NO:50
PPEYMEAIYPVRSNSTIARG SEQ ID NO:51
APPEYMEA             SEQ ID NO:52
APPEYMEAI            SEQ ID NO:53
APPEYMEAIY           SEQ ID NO:54
APPEYMEAIYP          SEQ ID NO:55
APPEYMEAIYPV         SEQ ID NO:56
APPEYMEAIYPVR        SEQ ID NO:57
APPEYMEAIYPVRS       SEQ ID NO:58
APPEYMEAIYPVRSN      SEQ ID NO:59
APPEYMEAIYPVRSNS     SEQ ID NO:60
APPEYMEAIYPVRSNST    SEQ ID NO:61
APPEYMEAIYPVRSNSTI   SEQ ID NO:62
APPEYMEAIYPVRSNSTIA  SEQ ID NO:63
APPEYMEAIYPVRSNSTIAR SEQ ID NO:64
TAPPEYME             SEQ ID NO:65
TAPPEYMEA            SEQ ID NO:66
TAPPEYMEAI           SEQ ID NO:67
TAPPEYMEAIY          SEQ ID NO:68
TAPPEYMEAIYP         SEQ ID NO:69
TAPPEYMEAIYPV        SEQ ID NO:70
TAPPEYMEAIYPVR       SEQ ID NO:71
TAPPEYMEAIYPVRS      SEQ ID NO:72
TAPPEYMEAIYPVRSN     SEQ ID NO:73
TAPPEYMEAIYPVRSNS    SEQ ID NO:74
TAPPEYMEAIYPVRSNST   SEQ ID NO:75
TAPPEYMEAIYPVRSNSTI  SEQ ID NO:76
TAPPEYMEAIYPVRSNSTIA SEQ ID NO:77
PTAPPEYM             SEQ ID NO:78
PTAPPEYME            SEQ ID NO:79
PTAPPEYMEA           SEQ ID NO:80
PTAPPEYMEAI          SEQ ID NO:81
PTAPPEYMEAIY         SEQ ID NO:82
PTAPPEYMEAIYP        SEQ ID NO:83
PTAPPEYMEAIYPV       SEQ ID NO:84
PTAPPEYMEAIYPVR      SEQ ID NO:85
PTAPPEYMEAIYPVRS     SEQ ID NO:86
PTAPPEYMEAIYPVRSN    SEQ ID NO:87
PTAPPEYMEAIYPVRSNS   SEQ ID NO:88
PTAPPEYMEAIYPVRSNST  SEQ ID NO:89
PTAPPEYMEAIYPVRSNSTI SEQ ID NO:90
LPTAPPEY             SEQ ID NO:91
LPTAPPEYM            SEQ ID NO:92
LPTAPPEYME           SEQ ID NO:93
LPTAPPEYMEA          SEQ ID NO:94
LPTAPPEYMEAI         SEQ ID NO:95
LPTAPPEYMEAIY        SEQ ID NO:96
LPTAPPEYMEAIYP       SEQ ID NO:97
LPTAPPEYMEAIYPV      SEQ ID NO:98
LPTAPPEYMEALYPVR     SEQ ID NO:99
LPTAPPEYMEAIYPVRS    SEQ ID NO:100
LPTAPPEYMEAIYPVRSN   SEQ ID NO:101
LPTAPPEYMEAIYPVRSNS  SEQ ID NO:102
LPTAPPEYMEAIYPVRSNST SEQ ID NO:103
ILPTAPPEY            SEQ ID NO:104
ILPTAPPEYM           SEQ ID NO:105
ILPTAPPEYME          SEQ ID NO:106
ILPTAPPEYMEA         SEQ ID NO:107
ILPTAPPEYMEAI        SEQ ID NO:108
ILPTAPPEYMEAIY       SEQ ID NO:109
ILPTAPPEYMEAIYP      SEQ ID NO:110
ILPTAPPEYMEAIYPV     SEQ ID NO:111
ILPTAPPEYMEAIYPVR    SEQ ID NO:112
ILPTAPPEYMEAIYPVRS   SEQ ID NO:113
ILPTAPPEYMEAIYPVRSN  SEQ ID NO:114
ILPTAPPEYMEAIYPVRSNS SEQ ID NO:115
VILPTAPPEY           SEQ ID NO:116
VILPTAPPEYM          SEQ ID NO:117
VILPTAPPEYME         SEQ ID NO:118
VILPTAPPEYMEA        SEQ ID NO:119
VILPTAPPEYMEAI       SEQ ID NO:120
VILPTAPPEYMEAIY      SEQ ID NO:121
VILPTAPPEYMEAIYP     SEQ ID NO:122
VILPTAPPEYMEAIYPV    SEQ ID NO:123
VILPTAPPEYMEAIYPVR   SEQ ID NO:124
VILPTAPPEYMEAIYPVRS  SEQ ID NO:125
VILPTAPPEYMEAIYPVRSN SEQ ID NO:126
RVTLPTAPPEY          SEQ ID NO:127
RVLLPTAPPEYM         SEQ ID NO:128
RVILPTAPPEYME        SEQ ID NO:129
RVILPTAPPEYMEA       SEQ ID NO:130
RVILPTAPPEYMEAI      SEQ ID NO:131
RVILPTAPPEYMEAIY     SEQ ID NO:132
RVILPTAPPEYMEAIYP    SEQ ID NO:133
RVILPTAPPEYMEAIYPV   SEQ ID NO:134
RVILPTAPPEYMEAIYPVR  SEQ ID NO:135
RVILPTAPPEYMEAIYPVRS SEQ ID NO:136
RRVILPTAPPEY         SEQ ID NO:137
RRVILPTAPPEYM        SEQ ID NO:138
RRVILPTAPPEYME       SEQ ID NO:139
RRVILPTAPPEYMEA      SEQ ID NO:140
RRVILPTAPPEYMEAI     SEQ ID NO:141
RRVILPTAPPEYMEAIY    SEQ ID NO:142
RRVILPTAPPEYMEAIYP   SEQ ID NO:143
RRVILPTAPPEYMEAIYPV  SEQ ID NO:144
RRVILPTAPPEYMEAIYPVR SEQ ID NO:145
MRRVILPTAPPEY        SEQ ID NO:146
MRRVILPTAPPEYM       SEQ ID NO:147
MRRVILPTAPPEYME      SEQ ID NO:148
MRRVILPTAPPEYMEA     SEQ ID NO:149
MRRVILPTAPPEYMEAI    SEQ ID NO:150
MRRVILPTAPPEYMEAIY   SEQ ID NO:151
MRRVILPTAPPEYMEAIYP  SEQ ID NO:152
MRRVILPTAPPEYMEAIYPV SEQ ID NO:153

[0112]

TABLE 3
PPXY Motif Containing Peptides from Marburg Virus
VP40 Protein
(GenBank Accession No. NP_042027)
PPPYADHG             SEQ ID NO:154
PPPYADHGA            SEQ ID NO:155
PPPYADHGAN           SEQ ID NO:156
PPPYADHGANQ          SEQ ID NO:157
PPPYADHGANQL         SEQ ID NO:158
PPPYADHGANQLI        SEQ ID NO:159
PPPYADHGANQLIP       SEQ ID NO:160
PPPYADHGANQLIPA      SEQ ID NO:161
PPPYADHGANQLIPAD     SEQ ID NO:162
PPPYADHGANQLIPADQ    SEQ ID NO:163
PPPYADHGANQLIPADQL   SEQ ID NO:164
PPPYADHGANQLIPADQLS  SEQ ID NO:165
PPPYADHGANQLIPADQLSN SEQ ID NO:166
NPPPYADH             SEQ ID NO:167
NPPPYADHG            SEQ ID NO:168
NPPPYADHGA           SEQ ID NO:169
NFPPYADHGAN          SEQ ID NO:170
NPPPYADHGANQ         SEQ ID NO:171
NPPPYADHGANQL        SEQ ID NO:172
NPPPYADHGANQLI       SEQ ID NO:173
NPPPYADHGANQLIP      SEQ ID NO:174
NPPPYADHGANQLIPA     SEQ ID NO:175
NPPPYADHGANQLIPAD    SEQ ID NO:176
NPPPYADHGANQLIPADQ   SEQ ID NO:177
NPPPYADHGANQLIPADQL  SEQ ID NO:178
NIPPYADHGANQLIPADQLS SEQ ID NO:179
LNPPPYAD             SEQ ID NO:180
LNPPPYADH            SEQ ID NO:181
LNPPPYADHG           SEQ ID NO:182
LNPPPYADHGA          SEQ ID NO:183
LNPPPYADHGAN         SEQ ID NO:184
LNPPPYADHGANQ        SEQ ID NO:185
LNPPPYADHGANQL       SEQ ID NO:186
LNPPPYADHGANQLI      SEQ ID NO:187
LNPPPYADHGANQLIP     SEQ ID NO:188
LNPPPYADHGANQLIPA    SEQ ID NO:189
LNPPPYADHGANQLIPAD   SEQ ID NO:190
LNPPPYADHGANQLIPADQ  SEQ ID NO:191
LNPPPYADHGANQLIPADQL SEQ ID NO:192
YLNPPPYA             SEQ ID NO:193
YLNPPPYAD            SEQ ID NO:194
YLNPPPYADH           SEQ ID NO:195
YLNPPPYADHG          SEQ ID NO:196
YLNPPPYADHGA         SEQ ID NO:197
YLNPPPYADHGAN        SEQ ID NO:198
YLNPPPYADHGANQ       SEQ ID NO:199
YLNPPPYADHGANQL      SEQ ID NO:200
YLNPPPYADHGANQLI     SEQ ID NO:201
YLNPPPYADHGANQLIP    SEQ ID NO:202
YLNPPPYADHGANQLIPA   SEQ ID NO:203
YLNPPPYADHGANQLIPAD  SEQ ID NO:204
YLNPPPYADHGANQLTPADQ SEQ ID NO:205
QYLNPPPY             SEQ ID NO:206
QYLNPPPYA            SEQ ID NO:207
QYLNPPPYAD           SEQ ID NO:208
QYLNPPPYADH          SEQ ID NO:209
QYLNPPPYADHG         SEQ ID NO:210
QYLNPPPYADHGA        SEQ ID NO:211
QYLNPPPYADHGAN       SEQ ID NO:212
QYLNPPPYADHGANQ      SEQ ID NO:213
QYLNPPPYADHGANQL     SEQ ID NO:214
QYLNPPPYADHGANQLI    SEQ ID NO:215
QYLNPPPYADHGANQLIP   SEQ ID NO:216
QYLNPPPYADHGANQLIPA  SEQ ID NO:217
QYLNPPPYADHGANQLIPAD SEQ ID NO:218
MQYLNPPPY            SEQ ID NO:219
MQYLNPPPYA           SEQ ID NO:220
MQYLNPPPYAD          SEQ ID NO:221
MQYLNPPPYADH         SEQ ID NO:222
MQYLNPPPYADHG        SEQ ID NO:223
MQYLNPPPYADHGA       SEQ ID NO:224
MQYLNPPPYADHGAN      SEQ ID NO:225
MQYLNPPPYADHGANQ     SEQ ID NO:226
MQYLNPPPYADHGANQL    SEQ ID NO:227
MQYLNPPPYADHGANQLI   SEQ ID NO:228
MQYLNPPPYADHGANQLIP  SEQ ID NO:229
MQYLNPPPYADHGANQLIPA SEQ ID NO:230
YMQYLNPPPY           SEQ ID NO:231
YMQYLNPPPYA          SEQ ID NO:232
YMQYLNPPPYAD         SEQ ID NO:233
YMQYLNPPPYADH        SEQ ID NO:234
YMQYLNPPPYADHG       SEQ ID NO:235
YMQYLNPPPYADHGA      SEQ ID NO:236
YMQYLNPPPYADHGAN     SEQ ID NO:237
YMQYLNPPPYADHGANQ    SEQ ID NO:238
YMQYLNPPPYADHGANQL   SEQ ID NO:239
YMQYLNPPPYADHGANQLI  SEQ ID NO:240
YMQYLNPPPYADHGANQLIP SEQ ID NO:241
TYMQYLNPPPY          SEQ ID NO:242
TYMQYLNPPPYA         SEQ ID NO:243
TYMQYLNPPPYAD        SEQ ID NO:244
TYMQYLNPPPYADH       SEQ ID NO:245
TYMQYLNPPPYADHG      SEQ ID NO:246
TYMQYLNPPPYADHGA     SEQ ID NO:247
TYMQYLNPPPYADHGAN    SEQ ID NO:248
TYMQYLNPPPYADHGANQ   SEQ ID NO:249
TYMQYLNPPPYADHGANQL  SEQ ID NO:250
TYMQYLNPPPYADHGANQLI SEQ ID NO:251
NTYMQYLNPPPY         SEQ ID NO:252
NTYMQYLNPPPYA        SEQ ID NO:253
NTYMQYLNPPPYAD       SEQ ID NO:254
NTYMQYLNPPPYADH      SEQ ID NO:255
NTYMQYLNPPPYADHG     SEQ ID NO:256
NTYMQYLNPPPYADHGA    SEQ ID NO:257
NTYMQYLNPPPYADHGAN   SEQ ID NO:258
NTYMQYLNPPPYADHGANQ  SEQ ID NO:259
NTYMQYLNPPPYADHGANQL SEQ ID NO:260
YNTYMQYLNPPPY        SEQ ID NO:261
YNTYMQYLNPPPYA       SEQ ID NO:262
YNTYMQYLNPPPYAD      SEQ ID NO:263
YNTYMQYLNPPPYADH     SEQ ID NO:264
YNTYMQYLNPPPYADHG    SEQ ID NO:265
YNTYMQYLNPPPYADHGA   SEQ ID NO:266
YNTYMQYLNPPPYADHGAN  SEQ ID NO:267
YNTYMQYLNPPPYADHGANQ SEQ ID NO:268
NYNTYMQYLNPPPY       SEQ ID NO:269
NYNTYMQYLNPPPYA      SEQ ID NO:270
NYNTYMQYLNPPPYAD     SEQ ID NO:271
NYNTYMQYLNPPPYADH    SEQ ID NO:272
NYNTYMQYLNPPPYADHG   SEQ ID NO:273
NYNTYMQYLNPPPYADHGA  SEQ ID NO:274
NYNTYMQYLNPPPYADHGAN SEQ ID NO:275
SNYNTYMQYLNPPPY      SEQ ID NO:276
SNYNTYMQYLNPPPYA     SEQ ID NO:277
SNYNTYMQYLNPPPYAD    SEQ ID NO:278
SNYNTYMQYLNPPPYADH   SEQ ID NO:279
SNYNTYMQYLNPPPYADHG  SEQ ID NO:280
SNYNTYMQYLNPPPYADHGA SEQ ID NO:281
SSNYNTYMQYLNPPPY     SEQ ID NO:282
SSNYNTYMQYLNPPPYA    SEQ ID NO:283
SSNYNTYMQYLNPPPYAD   SEQ ID NO:284
SSNYNTYMQYLNPPPYADH  SEQ ID NO:285
SSNYNTYMQYLNPPPYADHG SEQ ID NO:286
SSSNYNTYMQYLNPPPY    SEQ ID NO:287
SSSNYNTYMQYLNPPPYA   SEQ ID NO:288
SSSNYNTYMQYLNPPPYAD  SEQ ID NO:289
SSSNYNTYMQYLNPPPYADH SEQ ID NO:290
ASSSNYNTYMQYLNPPPY   SEQ ID NO:291
ASSSNYNTYMQYLNPPPYA  SEQ ID NO:292
ASSSNYNTYMQYLNPPPYAD SEQ ID NO:293
MASSSNYNTYMQYLNPPPY  SEQ ID NO:294
MASSSNYNTYMQYLNPPPYA SEQ ID NO:295

[0113]

TABLE 4
PPXY Motif Containing Peptides from Vesicular
Stomatitis Virus Matrix Protein
(GenBank Accession No. P04876)
PPPY                  EEDT       SEQ ID NO:296
PPPY                  EEDTS      SEQ ID NO:297
PPPY                  EEDTSM     SEQ ID NO:298
PPPY                  EEDTSME    SEQ ID NO:299
PPPY                  EEDTSMEY   SEQ ID NO:300
PPPY                  EEDTSMEYA  SEQ ID NO:301
PPPY                  EEDTSMEYAP SEQ ID NO:302
PPPY                  EEDTSMEYAPS SEQ ID NO:303
PPPY                  EEDTSMEYAPSA SEQ ID NO:304
PPPY                  EEDTSMEYAPSAP SEQ ID NO:305
PPPY                  EEDTSMEYAPSAPI SEQ ID NO:306
PPPY                  EEDTSMEYAPSAPID SEQ ID NO:307
PPPY                  EEDTSMEYAPSAPIDK SEQ ID NO:308
APPPYEED                         SEQ ID NO:309
APPPYEEDT                        SEQ ID NO:310
APPPYEEDTS                       SEQ ID NO:311
APPPYEEDTSM                      SEQ ID NO:312
APPPYEEDTSME                     SEQ ID NO:313
APPPYEEDTSMEY                    SEQ ID NO:314
APPPYEEDTSMEYA                   SEQ ID NO:315
APPPYEEDTSMEYAP                  SEQ ID NO:316
APPPYEEDTSMEYAPS                 SEQ ID NO:317
APPPYEEDTSMEYAPSA                SEQ ID NO:318
APPPYEEDTSMEYAPSAP               SEQ ID NO:319
APPPYEEDTSMEYAPSAPI              SEQ ID NO:320
APPPYEEDTSMEYAPSAPID             SEQ ID NO:321
IAPPPYEE                         SEQ ID NO:322
IAPPPYEED                        SEQ ID NO:323
IAPPPYEEDT                       SEQ ID NO:324
IAPPPYEEDTS                      SEQ ID NO:325
IAPPPYEEDTSM                     SEQ ID NO:326
IAPPPYEEDTSME                    SEQ ID NO:327
IAPPPYEEDTSMEY                   SEQ ID NO:328
IAPPPYEEDTSMEYA                  SEQ ID NO:329
IAPPPYEEDTSMEYAP                 SEQ ID NO:330
IAPPPYEEDTSMEYAPS                SEQ ID NO:331
IAPPPYEEDTSMEYAPSA               SEQ ID NO:332
IAPPPYEEDTSMEYAPSAP              SEQ ID NO:333
IAPPPYEEDTSMEYAPSAPI             SEQ ID NO:334
GIAPPPYE                         SEQ ID NO:335
GIAPPPYEE                        SEQ ID NO:336
GIAPPPYEED                       SEQ ID NO:337
GIAPPPYEEDT                      SEQ ID NO:338
GIAPPPYEEDTS                     SEQ ID NO:339
GIAPPPYEEDTSM                    SEQ ID NO:340
GIAPPPYEEDTSME                   SEQ ID NO:341
GIAPPPYEEDTSMEY                  SEQ ID NO:342
GIAPPPYEEDTSMEYA                 SEQ ID NO:343
GIAPPPYEEDTSMEYAP                SEQ ID NO:344
GIAPPPYEEDTSMEYAPS               SEQ ID NO:345
GIAPPPYEEDTSMEYAPSA              SEQ ID NO:346
GIAPPPYEEDTSMEYAPSAP             SEQ ID NO:347
LGIAPPPY                         SEQ ID NO:348
LGIAPPPYE                        SEQ ID NO:349
LGIAPPPYEE                       SEQ ID NO:350
LGIAPPPYEED                      SEQ ID NO:351
LGIAPPPYEEDT                     SEQ ID NO:352
LGIAPPPYEEDTS                    SEQ ID NO:353
LGIAPPPYEEDTSM                   SEQ ID NO:354
LGIAPPPYEEDTSME                  SEQ ID NO:355
LGIAPPPYEEDTSMEY                 SEQ ID NO:356
LGIAPPPYEEDTSMEYA                SEQ ID NO:357
LGIAPPPYEEDTSMEYAP               SEQ ID NO:358
LGIAPPPYEEDTSMEYAPS              SEQ ID NO:359
LGIAPPPYEEDTSMEYAPSA             SEQ ID NO:360
KLGIAPPPY                        SEQ ID NO:361
KLGIAPPPYE                       SEQ ID NO:362
KLGIAPPPYEE                      SEQ ID NO:363
KLGIAPPPYEED                     SEQ ID NO:364
KLGIAPPPYEEDT                    SEQ ID NO:365
KLGIAPPPYEEDTS                   SEQ ID NO:366
KLGIAPPPYEEDTSM                  SEQ ID NO:367
KLGLAPPPYEEDTSME                 SEQ ID NO:368
KLGIAPPPYEEDTSMEY                SEQ ID NO:369
KLGIAPPPYEEDTSMEYA               SEQ ID NO:370
KLGIAPPPYEEDTSMEYAP              SEQ ID NO:371
KLGIAPPPYEEDTSMEYAPS             SEQ ID NO:372
KKLGIAPPPY                       SEQ ID NO:373
KKLGIAPPPYE                      SEQ ID NO:374
KKLGLAPPPYEE                     SEQ ID NO:375
KKLGIAPPPYEED                    SEQ ID NO:376
KKLGIAPPPYEEDT                   SEQ ID NO:377
KKLGIAPPPYEEDTS                  SEQ ID NO:378
KKLGIAPPPYEEDTSM                 SEQ ID NO:379
KKLGIAPPPYEEDTSME                SEQ ID NO:380
KKLGIAPPPYEEDTSMEY               SEQ ID NO:381
KKLGIAPPPYEEDTSMEYA              SEQ ID NO:382
KKLGIAPPPYEEDTSMEYAP             SEQ ID NO:383
SKKLGIAPPPY                      SEQ ID NO:384
SKKLGIAPPPYE                     SEQ ID NO:385
SKKLGIAPPPYEE                    SEQ ID NO:386
SKKLGIAPPPYEED                   SEQ ID NO:387
SKKLGIAPPPYEEDT                  SEQ ID NO:388
SKKLGIAPPPYEEDTS                 SEQ ID NO:389
SKKLGIAPPPYEEDTSM                SEQ ID NO:390
SKKLGIAPPPYEEDTSME               SEQ ID NO:391
SKKLGIAPPPYEEDTSMEY              SEQ ID NO:392
SKKLGIAPPPYEEDTSMEYA             SEQ ID NO:393
KSKKLGIAPPPY                     SEQ ID NO:394
KSKKLGIAPPPYE                    SEQ ID NO:395
KSKKLGIAPPPYEE                   SEQ ID NO:396
KSKKLGIAPPPYEED                  SEQ ID NO:397
KSKKLGIAPPPYEEDT                 SEQ ID NO:398
KSKKLGIAPPPYEEDTS                SEQ ID NO:399
KSKKLGIAPPPYEEDTSM               SEQ ID NO:400
KSKKLGIAPPPYEEDTSME              SEQ ID NO:401
KSKKLGIAPPPYEEDTSMEY             SEQ ID NO:402
KKSKKLGIAPPPY                    SEQ ID NO:403
KKSKKLGIAPPPYE                   SEQ ID NO:404
KKSKKLGIAPPPYEE                  SEQ ID NO:405
KKSKKLGIAPPPYEED                 SEQ ID NO:406
KKSKKLGIAPPPYEEDT                SEQ ID NO:407
KKSKKLGIAPPPYEEDTS               SEQ ID NO:408
KKSKKLGIAPPPYEEDTSM              SEQ ID NO:409
KKSKKLGIAPPPYEEDTSME             SEQ ID NO:410
GKKSKKLGIAPPPY                   SEQ ID NO:411
GKKSKKLGIAPPPYE                  SEQ ID NO:412
GKKSKKLGIAPPPYEE                 SEQ ID NO:413
GKKSKKLGIAPPPYEED                SEQ ID NO:414
GKKSKKLGIAPPPYEEDT               SEQ ID NO:415
GKKSKKLGIAPPPYEEDTS              SEQ ID NO:416
GKKSKKLGIAPPPYEEDTSM             SEQ ID NO:417
KGKKSKKLGIAPPPY                  SEQ ID NO:418
KGKKSKKLGIAPPPYE                 SEQ ID NO:419
KGKKSKKLGIAPPPYEE                SEQ ID NO:420
KGKKSKKLGIAPPPYEED               SEQ ID NO:421
KGKKSKKLGLAPPPYEEDT              SEQ ID NO:422
KGKKSKKLGIAPPPYEEDTS             SEQ ID NO:423
GKGKKSKKLGIAPPPY                 SEQ ID NO:424
GKGKKSKKLGIAPPPYE                SEQ ID NO:425
GKGKKSKKLGIAPPPYEE               SEQ ID NO:426
GKGKKSKKLGIAPPPYEED              SEQ ID NO:427
GKGKKSKKLGIAPPPYEEDT             SEQ ID NO:428
KGKGKKSKKLGIAPPPY                SEQ ID NO:429
KGKGKKSKKLGIAPPPYE               SEQ ID NO:430
KGKGKKSKKLGIAPPPYEE              SEQ ID NO:431
KGKGKKSKKLGIAPPPYEED             SEQ ID NO:432
LKGKGKKSKKLGIAPPPY               SEQ ID NO:433
LKGKGKKSKKLGIAPPPYE              SEQ ID NO:434
LKGKGKKSKKLGIAPPPYEE             SEQ ID NO:435
GLKGKGKKSKKLGIAPPPY              SEQ ID NO:436
GLKGKGKKSKKLGIAPPPYE             SEQ ID NO:437
LGLKGKGKKSKKLGIAPPPY             SEQ ID NO:438

[0114]

TABLE 5
PPPY Motif Containing Peptides from Rous Sarcoma
Virus GAG Protein
(Genbank Accession No. AAA19608)
PPPY                  VGSG       SEQ ID NO:439
PPPY                  VGSGL      SEQ ID NO:440
PPPY                  VGSGLY     SEQ ID NO:441
PPPY                  VGSGLYP    SEQ ID NO:442
PPPY                  VGSGLYPS   SEQ ID NO:443
PPPY                  VGSGLYPSL  SEQ ID NO:444
PPPY                  VGSGLYPSLA SEQ ID NO:445
PPPY                  VGSGLYPSLAG SEQ ID NO:446
PPPY                  VGSGLYPSLAGV SEQ ID NO:447
PPPY                  VGSGLYPSLAGVG SEQ ID NO:448
PPPY                  VGSGLYPSLAGVGE SEQ ID NO:449
PPPY                  VGSGLYPSLAGVGEQ SEQ ID NO:450
PPPY                  VGSGLYPSLAGVGEQQ SEQ ID NO:451
PPPPYVGS                         SEQ ID NO:452
PPPPYVGSG                        SEQ ID NO:453
PPPPYVGSGL                       SEQ ID NO:454
PPPPYVGSGLY                      SEQ ID NO:455
PPPPYVGSGLYP                     SEQ ID NO:456
PPPPYVGSGLYPS                    SEQ ID NO:457
PPPPYVGSGLYPSL                   SEQ ID NO:458
PPPPYVGSGLYPSLA                  SEQ ID NO:459
PPPPYVGSGLYPSLAG                 SEQ ID NO:460
PPPPYVGSGLYPSLAGV                SEQ ID NO:461
PPPPYVGSGLYPSLAGVG               SEQ ID NO:462
PPPPYVGSGLYPSLAGVGE              SEQ ID NO:463
PPPPYVGSGLYPSLAGVGEQ             SEQ ID NO:464
APPPPYVG                         SEQ ID NO:465
APPPPYVGS                        SEQ ID NO:466
APPPPYVGSG                       SEQ ID NO:467
APPPPYVGSGL                      SEQ ID NO:468
APPPPYVGSGLY                     SEQ ID NO:469
APPPPYVGSGLYP                    SEQ ID NO:470
APPPPYVGSGLYPS                   SEQ ID NO:471
APPPPYVGSGLYPSL                  SEQ ID NO:472
APPPPYVGSGLYPSLA                 SEQ ID NO:473
APPPPYVGSGLYPSLAG                SEQ ID NO:474
APPPPYVGSGLYPSLAGV               SEQ ID NO:475
APPPPYVGSGLYPSLAGVG              SEQ ID NO:476
APPPPYVGSGLYPSLAGVGE             SEQ ID NO:477
SAPPPPYV                         SEQ ID NO:478
SAPPPPYVG                        SEQ ID NO:479
SAPPPPYVGS                       SEQ ID NO:480
ATATASAPPPPYVGSGL                SEQ ID NO:523
ATATASAPPPPYVGSGLY               SEQ ID NO:524
ATATASAPPPPYVGSGLYP              SEQ ID NO:525
ATASAPPPPYVGSGLYPSLA             SEQ ID NO:526
TATASAPPPPY                      SEQ ID NO:527
TATASAPPPPYV                     SEQ ID NO:528
TATASAPPPPYVG                    SEQ ID NO:529
TATASAPPPPYVGS                   SEQ ID NO:530
TATASAPPPPYVGSG                  SEQ ID NO:531
TATASAPPPPYVGSGL                 SEQ ID NO:532
TATASAPPPPYVGSGLY                SEQ ID NO:533
TATASAPPPPYVGSGLYP               SEQ ID NO:534
TATASAPPPPYVGSGLYPS              SEQ ID NO:535
TATASAPPPPYVGSGLYPSL             SEQ ID NO:536
ATATASAPPPPY                     SEQ ID NO:537
ATATASAPPPPYV                    SEQ ID NO:538
ATATASAPPPPYVG                   SEQ ID NO:539
ATATASAPPPPYVGS                  SEQ ID NO:540
ATATASAPPPPYVGSG                 SEQ ID NO:541
ATATASAPPPPYVGSGL                SEQ ID NO:542
ATATASAPPPPYVGSGLY               SEQ ID NO:543
ATATASAPPPPYVGSGLYP              SEQ ID NO:544
ATATASAPPPPYVGSGLYPS             SEQ ID NO:545
CATATASAPPPPY                    SEQ ID NO:546
CATATASAPPPPYV                   SEQ ID NO:547
CATATASAPPPPYVG                  SEQ ID NO:548
CATATASAPPPPYVGS                 SEQ ID NO:549
CATATASAPPPPYVGSG                SEQ ID NO:550
CATATASAPPPPYVGSGL               SEQ ID NO:551
CATATASAPPPPYVGSGLY              SEQ ID NO:552
CATATASAPPPPYVGSGLYP             SEQ ID NO:553
NCATATASAPPPPY                   SEQ ID NO:554
NCATATASAPPPPYV                  SEQ ID NO:555
NCATATASAPPPPYVG                 SEQ ID NO:556
NCATATASAPPPPYVGS                SEQ ID NO:557
NCATATASAPPPPYVGSG               SEQ ID NO:558
NCATATASAPPPPYVGSGL              SEQ ID NO:559
NCATATASAPPPPYVGSGLY             SEQ ID NO:560
CNCATATASAPPPPY                  SEQ ID NO:561
CNCATATASAPPPPYV                 SEQ ID NO:562
CNCATATASAPPPPYVG                SEQ ID NO:563
CNCATATASAPPPPYVGS               SEQ ID NO:564
CNCATATASAPPPPYVGSG              SEQ ID NO:565
CNCATATASAPPPPYVGSGL             SEQ ID NO:566
GCNCATATASAPPPPY                 SEQ ID NO:567
GCNCATATASAPPPPYV                SEQ ID NO:568
GCNCATATASAPPPPYVG               SEQ ID NO:569
SAPPPPYVGSG                      SEQ ID NO:481
SAPPPPYVGSGL                     SEQ ID NO:482
SAPPPPYVGSGLY                    SEQ ID NO:483
SAPPPPYVGSGLYP                   SEQ ID NO:484
SAPPPPYVGSGLYPS                  SEQ ID NO:485
SAPPPPYVGSGLYPSL                 SEQ ID NO:486
SAPPPPYVGSGLYPSLA                SEQ ID NO:487
SAPPPPYVGSGLYPSLAG               SEQ ID NO:488
SAPPPPYVGSGLYPSLAGV              SEQ ID NO:489
SAPPPPYVGSGLYPSLAGVG             SEQ ID NO:490
ASAPPPPY                         SEQ ID NO:491
ASAPPPPYV                        SEQ ID NO:492
ASAPPPPYVG                       SEQ ID NO:493
ASAPPPPYVGS                      SEQ ID NO:494
ASAPPPPYVGSG                     SEQ ID NO:495
ASAPPPPYVGSGL                    SEQ ID NO:496
ASAPPPPYVGSGLY                   SEQ ID NO:497
ASAPPPPYVGSGLYP                  SEQ ID NO:498
ASAPPPPYVGSGLYPS                 SEQ ID NO:499
ASAPPPPYVGSGLYPSL                SEQ ID NO:500
ASAPPPPYVGSGLYPSLA               SEQ ID NO:501
ASAPPPPYVGSGLYPSLAG              SEQ ID NO:502
ASAPPPPYVGSGLYPSLAGV             SEQ ID NO:503
TASAPPPPY                        SEQ ID NO:504
TASAPPPPYV                       SEQ ID NO:505
TASAPPPPYVG                      SEQ ID NO:506
TASAPPPPYVGS                     SEQ ID NO:507
TASAPPPPYVGSG                    SEQ ID NO:508
TASAPPPPYVGSGL                   SEQ ID NO:509
TASAPPPPYVGSGLY                  SEQ ID NO:510
TASAPPPPYVGSGLYP                 SEQ ID NO:511
TASAPPPPYVGSGLYPS                SEQ ID NO:512
TASAPPPPYVGSGLYPSL               SEQ ID NO:513
TASAPPPPYVGSGLYPSLA              SEQ ID NO:514
TASAPPPPYVGSGLYPSLAG             SEQ ID NO:515
ATASAPPPPY                       SEQ ID NO:516
ATASAPPPPYV                      SEQ ID NO:517
ATASAPPPPYVG                     SEQ ID NO:518
ATASAPPPPYVGS                    SEQ ID NO:519
ATASAPPPPYVGSG                   SEQ ID NO:520
ATASAPPPPYVGSGL                  SEQ ID NO:521
ATASAPPPPYVGSGLY                 SEQ ID NO:522
GCNCATATASAPPPPYVGS              SEQ ID NO:570
GCNCATATASAPPPPYVGSG             SEQ ID NO:571
VGCNCATATASAPPPPY                SEQ ID NO:572
VGCNCATATASAPPPPYV               SEQ ID NO:573
VGCNCATATASAPPPPYVG              SEQ ID NO:574
VGCNCATATASAPPPPYVGS             SEQ ID NO:575
AVGCNCATATASAPPPPY               SEQ ID NO:576
AVGCNCATATASAPPPPYV              SEQ ID NO:577
AVGCNCATATASAPPPPYVG             SEQ ID NO:578
TAVGCNCATATASAPPPPY              SEQ ID NO:579
TAVGCNCATATASAPPPPYV             SEQ ID NO:580
GTAVGCNCATATASAPPPPY             SEQ ID NO:581
PPEY                  MEAI       SEQ ID NO:39
PPEY                  MEAIY      SEQ ID NO:40
PPEY                  MEAIYP     SEQ ID NO:41
PPEY                  MEAIYPV    SEQ ID NO:42
PPEY                  MEAIYPVR   SEQ ID NO:43
PPEY                  MEAIYPVRS  SEQ ID NO:44
PPEY                  MEAIYPVRSN SEQ ID NO:45
PPEY                  MEAIYPVRSNS SEQ ID NO:46
PPEY                  MEAIYPVRSNST SEQ ID NO:47
PPEY                  MEAIYPVRSNSTI SEQ ID NO:48
PPEY                  MEAIYPVRSNSTIA SEQ ID NO:49
PPEY                  MEAIYPVRSNSTIAR SEQ ID NO:50
PPEY                  MEAIYPVRSNSTIARG SEQ ID NO:51
APPEYMEA                         SEQ ID NO:52
APPEYMEAI                        SEQ ID NO:53
APPEYMEAIY                       SEQ ID NO:54
APPEYMEAIYP                      SEQ ID NO:55
APPEYMEAIYPV                     SEQ ID NO:56
APPEYMEAIYPVR                    SEQ ID NO:57
APPEYMEAIYPVRS                   SEQ ID NO:58
APPEYMEAIYPVRSN                  SEQ ID NO:59
APPEYMEAIYPVRSNS                 SEQ ID NO:60
APPEYMEAIYPVRSNST                SEQ ID NO:61
APPEYMEAIYPVRSNSTI               SEQ ID NO:62
APPEYMEAIYPVRSNSTIA              SEQ ID NO:63
APPEYMEAIYPVRSNSTIAR             SEQ ID NO:64
TAPPEYME                         SEQ ID NO:65
TAPPEYMEA                        SEQ ID NO:66
TAPPEYMEAI                       SEQ ID NO:67
TAPPEYMEAIY                      SEQ ID NO:68
TAPPEYMEAIYP                     SEQ ID NO:69
TAPPEYMEAIYPV                    SEQ ID NO:70
TAPPEYMEAIYPVR                   SEQ ID NO:71
TAPPEYMEAIYPVRS                  SEQ ID NO:72
TAPPEYMEAIYPVRSN                 SEQ ID NO:73
TAPPEYMEAIYPVRSNS                SEQ ID NO:74
TAPPEYMEAIYPVRSNST               SEQ ID NO:75
TAPPEYMEAIYPVRSNSTI              SEQ ID NO:76
TAPPEYMEAIYPVRSNSTIA             SEQ ID NO:77
PTAPPEYM                         SEQ ID NO:78
PTAPPEYME                        SEQ ID NO:79
PTAPPEYMEA                       SEQ ID NO:80
PTAPPEYMEAI                      SEQ ID NO:81
PTAPPEYMEAIY                     SEQ ID NO:82
PTAPPEYMEAIYP                    SEQ ID NO:83
PTAPPEYMEAIYPV                   SEQ ID NO:84
PTAPPEYMEAIYPVR                  SEQ ID NO:85
PTAPPEYMEAIYPVRS                 SEQ ID NO:86
PTAPPEYMEAIYPVRSN                SEQ ID NO:87
PTAPPEYMEAIYPVRSNS               SEQ ID NO:88
PTAPPEYMEAIYPVRSNST              SEQ ID NO:89
PTAPPEYMEAIYPVRSNSTI             SEQ ID NO:90
LPTAPPEY                         SEQ ID NO:91
LPTAPPEYM                        SEQ ID NO:92
LPTAPPEYME                       SEQ ID NO:93
LPTAPPEYMEA                      SEQ ID NO:94
LPTAPPEYMEAI                     SEQ ID NO:95
LPTAPPEYMEAIY                    SEQ ID NO:96
LPTAPPEYMEAIYP                   SEQ ID NO:97
LPTAPPEYMEAIYPV                  SEQ ID NO:98
LPTAPPEYMEAIYPVR                 SEQ ID NO:99
LPTAPPEYMEAIYPVRS                SEQ ID NO:100
LPTAPPEYMEAIYPVRSN               SEQ ID NO:101
LPTAPPEYMEAIYPVRSNS              SEQ ID NO:102
LPTAPPEYMEAIYPVRSNST             SEQ ID NO:103
ILPTAPPEY                        SEQ ID NO:104
ILPTAPPEYM                       SEQ ID NO:105
ILPTAPPEYME                      SEQ ID NO:106
ILPTAPPEYMEA                     SEQ ID NO:107
ILPTAPPEYMEAI                    SEQ ID NO:108
ILPTAPPEYMEAIY                   SEQ ID NO:109
ILPTAPPEYMEAIYP                  SEQ ID NO:110
ILPTAPPEYMEAIYPV                 SEQ ID NO:111
ILPTAPPEYMEAIYPVR                SEQ ID NO:112
ILPTAPPEYMEAIYPVRS               SEQ ID NO:113
ILPTAPPEYMEAIYPVRSN              SEQ ID NO:114
ILPTAPPEYMEAIYPVRSNS             SEQ ID NO:115
VILPTAPPEY                       SEQ ID NO:116
VILPTAPPEYM                      SEQ ID NO:117
VILPTAPPEYME                     SEQ ID NO:118
VILPTAPPEYMEA                    SEQ ID NO:119
VILPTAPPEYMEAI                   SEQ ID NO:120
VILPTAPPEYMEAIY                  SEQ ID NO:121
VILPTAPPEYMEAIYP                 SEQ ID NO:122
VILPTAPPEYMEAIYPV                SEQ ID NO:123
VILPTAPPEYMEAIYPVR               SEQ ID NO:124
VILPTAPPEYMEAIYPVRS              SEQ ID NO:125
VILPTAPPEYMEAIYPVRSN             SEQ ID NO:126
RVILPTAPPEY                      SEQ ID NO:127
RVILPTAPPEYM                     SEQ ID NO:128
RVILPTAPPEYME                    SEQ ID NO:129
RVILPTAPPEYMEA                   SEQ ID NO:130
RVILPTAPPEYMEAI                  SEQ ID NO:131
RVILPTAPPEYMEAIY                 SEQ ID NO:132
RVILPTAPPEYMEAIYP                SEQ ID NO:133
RVILPTAPPEYMEAIYPV               SEQ ID NO:134
RVILPTAPPEYMEAIYPVR              SEQ ID NO:135
RVILPTAPPEYMEAIYPVRS             SEQ ID NO:136
RRVILPTAPPEY                     SEQ ID NO:137
RRVILPTAPPEYM                    SEQ ID NO:138
RRVILPTAPPEYME                   SEQ ID NO:139
RRVILPTAPPEYMEA                  SEQ ID NO:140
RRVILPTAPPEYMEAI                 SEQ ID NO:141
RRVILPTAPPEYMEAIY                SEQ ID NO:142
RRVILPTAPPEYMEAIYP               SEQ ID NO:143
RRVILPTAPPEYMEAIYPV              SEQ ID NO:144
RRVILPTAPPEYMEAIYPVR             SEQ ID NO:145
MRRVILPTAPPEY                    SEQ ID NO:146
MRRVILPTAPPEYM                   SEQ ID NO:147
MRRVILPTAPPEYME                  SEQ ID NO:148
MRRVILPTAPPEYMEA                 SEQ ID NO:149
MRRVILPTAPPEYMEAI                SEQ ID NO:150
MRRVILPTAPPEYMEAIY               SEQ ID NO:151
MRRVILPTAPPEYMEAIYP              SEQ ID NO:152
MRRVILPTAPPEYMEAIYPV             SEQ ID NO:153

[0115]

TABLE 6
PPXY Motif Containing Peptides from Hepatitis B
Virus Core Antigen
(GenBank Accession No. S53155)
PPPY                  RPPN       SEQ ID NO:582
PPPY                  RPPNA      SEQ ID NO:583
PPPY                  RPPNAP     SEQ ID NO:584
PPPY                  RPPNAPI    SEQ ID NO:585
PPPY                  RPPNAPIL   SEQ ID NO:586
PPPY                  RPPNAPILS  SEQ ID NO:587
PPPY                  RPPNAPILST SEQ ID NO:588
PPPY                  RPPNAPILSTL SEQ ID NO:589
PPPY                  RPPNAPILSTLP SEQ ID NO:590
PPPY                  RPPNAPILSTLPE SEQ ID NO:591
PPPY                  RPPNAPILSTLPET SEQ ID NO:592
PPPY                  RPPNAPILSTLPETT SEQ ID NO:593
PPPY                  RPPNAPILSTLPETTV SEQ ID NO:594
TPPPYRPP                         SEQ ID NO:595
TPPPYRPPN                        SEQ ID NO:596
TPPPYRPPNA                       SEQ ID NO:597
TPPPYRPPNAP                      SEQ ID NO:598
TPPPYRPPNAPI                     SEQ ID NO:599
TPPPYRPPNAPIL                    SEQ ID NO:600
TPPPYRPPNAPILS                   SEQ ID NO:601
TPPPYRPPNAPILST                  SEQ ID NO:602
TPPPYRPPNAPILSTL                 SEQ ID NO:603
TPPPYRPPNAPILSTLP                SEQ ID NO:604
TPPPYRPPNAPILSTLPE               SEQ ID NO:605
TPPPYRPPNAPILSTLPET              SEQ ID NO:606
TPPPYRPPNAPILSTLPETT             SEQ ID NO:607
RTPPPYRP                         SEQ ID NO:608
RTPPPYRPP                        SEQ ID NO:609
RTPPPYRPPN                       SEQ ID NO:610
RTPPPYRPPNA                      SEQ ID NO:611
RTPPPYRPPNAP                     SEQ ID NO:612
RTPPPYRPPNAPI                    SEQ ID NO:613
RTPPPYRPPNAPIL                   SEQ ID NO:614
RTPPPYRPPNAPILS                  SEQ ID NO:615
RTPPPYRPPNAPILST                 SEQ ID NO:616
RTPPPYRPPNAPILSTL                SEQ ID NO:617
RTPPPYRPPNAPILSTLP               SEQ ID NO:618
RTPPPYRPPNAPILSTLPE              SEQ ID NO:619
RTPPPYRPPNAPILSTLPET             SEQ ID NO:620
IRTPPPYR                         SEQ ID NO:621
IRTPPPYRP                        SEQ ID NO:622
IRTPPPYRPP                       SEQ ID NO:623
IRTPPPYRPPN                      SEQ ID NO:624
IRTPPPYRPPNA                     SEQ ID NO:625
IRTPPPYRPPNAP                    SEQ ID NO:626
IRTPPPYRPPNAPI                   SEQ ID NO:627
IRTPPPYRPPNAPIL                  SEQ ID NO:628
IRTPPPYRPPNAPILS                 SEQ ID NO:629
IRTPPPYRPPNAPILST                SEQ ID NO:630
IRTPPPYRPPNAPILSTL               SEQ ID NO:631
IRTPPPYRPPNAPILSTLP              SEQ ID NO:632
IRTPPPYRPPNAPILSTLPE             SEQ ID NO:633
WIRTPPPY                         SEQ ID NO:634
WIRTPPPYR                        SEQ ID NO:635
WIRTPPPYRP                       SEQ ID NO:636
WIRTPPPYRPP                      SEQ ID NO:637
WIRTPPPYRPPN                     SEQ ID NO:638
WIRTPPPYRPPNA                    SEQ ID NO:639
WIRTPPPYRPPNAP                   SEQ ID NO:640
WIRTPPPYRPPNAPI                  SEQ ID NO:641
WIRTPPPYRPPNAPIL                 SEQ ID NO:642
WIRTPPPYRPPNAPILS                SEQ ID NO:643
WIRTPPPYRPPNAPILST               SEQ ID NO:644
WIRTPPPYRPPNAPILSTL              SEQ ID NO:645
WIRTPPPYRPPNAPILSTLP             SEQ ID NO:646
VWIRTPPPY                        SEQ ID NO:647
VWIRTPPPYR                       SEQ ID NO:648
VWIRTPPPYRP                      SEQ ID NO:649
VWIRTPPPYRPP                     SEQ ID NO:650
VWIRTPPPYRPPN                    SEQ ID NO:651
VWIRTPPPYRPPNA                   SEQ ID NO:652
VWIRTPPPYRPPNAP                  SEQ ID NO:653
VWIRTPPPYRPPNAPI                 SEQ ID NO:654
VWIRTPPPYRPPNAPIL                SEQ ID NO:655
VWIRTPPPYRPPNAPILS               SEQ ID NO:656
VWIRTPPPYRPPNAPILST              SEQ ID NO:657
VWIRTPPPYRPPNAPILSTL             SEQ ID NO:658
GVWIRTPPPY                       SEQ ID NO:659
GVWIRTPPPYR                      SEQ ID NO:660
GVWIRTPPPYRP                     SEQ ID NO:661
GVWTRTPPPYRPP                    SEQ ID NO:662
GVWIRTPPPYRPPN                   SEQ ID NO:663
GVWIRTPPPYRPPNA                  SEQ ID NO:664
GVWIRTPPPYRPPNAP                 SEQ ID NO:665
GVWIRTPPPYRPPNAPI                SEQ ID NO:666
GVWIRTPPPYRPPNAPIL               SEQ ID NO:667
GVWIRTPPPYRPPNAPILS              SEQ ID NO:668
GVWIRTPPPYRPPNAPILST             SEQ ID NO:669
FGVWIRTPPPY                      SEQ ID NO:670
FGVWIRTPPPYR                     SEQ ID NO:671
FGVWIRTPPPYRP                    SEQ ID NO:672
FGVWIRTPPPYRPP                   SEQ ID NO:673
FGVWIRTPPPYRPPN                  SEQ ID NO:674
FGVWIRTPPPYRPPNA                 SEQ ID NO:675
FGVWIRTPPPYRPPNAP                SEQ ID NO:676
FGVWIRTPPPYRPPNAPI               SEQ ID NO:677
FGVWIRTPPPYRPPNAPIL              SEQ ID NO:678
FGVWIRTPPPYRPPNAPILS             SEQ ID NO:679
SFGVWIRTPPPY                     SEQ ID NO:680
SFGVWIRTPPPYR                    SEQ ID NO:681
SFGVWIRTPPPYRP                   SEQ ID NO:682
SFGVWIRTPPPYRPP                  SEQ ID NO:683
SFGVWIRTPPPYRPPN                 SEQ ID NO:684
SFGVWIRTPPPYRPPNA                SEQ ID NO:685
SFGVWIRTPPPYRPPNAP               SEQ ID NO:686
SFGVWIRTPPPYRPPNAPI              SEQ ID NO:687
SFGVWIRTPPPYRPPNAPIL             SEQ ID NO:688
VSFGVWIRTPPPY                    SEQ ID NO:689
VSFGVWIRTPPPYR                   SEQ ID NO:690
VSFGVWIRTPPPYRP                  SEQ ID NO:691
VSFGVWIRTPPPYRPP                 SEQ ID NO:692
VSFGVWIRTPPPYRPPN                SEQ ID NO:693
VSFGVWIRTPPPYRPPNA               SEQ ID NO:694
VSFGVWIRTPPPYRPPNAP              SEQ ID NO:695
VSFGVWIRTPPPYRPPNAPI             SEQ ID NO:696
LVSFGVWIRTPPPY                   SEQ ID NO:697
LVSFGVWIRTPPPYR                  SEQ ID NO:698
LVSFGVWIRTPPPYRP                 SEQ ID NO:699
LVSFGVWIRTPPPYRPP                SEQ ID NO:700
LVSFGVWIRTPPPYRPPN               SEQ ID NO:701
LVSFGVWTRTPPPYRPPNA              SEQ ID NO:702
LVSFGVWIRTPPPYRPPNAP             SEQ ID NO:703
YLVSFGVWIRTPPPY                  SEQ ID NO:704
YLVSFGVWIRTPPPYR                 SEQ ID NO:705
YLVSFGVWIRTPPPYRP                SEQ ID NO:706
YLVSFGVWIRTPPPYRPP               SEQ ID NO:707
YLVSFGVWIRTPPPYRPPN              SEQ ID NO:708
YLVSFGVWIRTPPPYRPPNA             SEQ ID NO:709
EYLVSFGVWIRTPPPY                 SEQ ID NO:710
EYLVSFGVWIRTPPPYR                SEQ ID NO:711
EYLVSFGVWIRTPPPYRP               SEQ ID NO:712
EYLVSFGVWIRTPPPYRPP              SEQ ID NO:713
EYLVSFGVWIRTPPPYRPPN             SEQ ID NO:714
IEYLVSFGVWIRTPPPY                SEQ ID NO:715
IEYLVSFGVWIRTPPPYR               SEQ ID NO:716
IEYLVSFGVWIRTPPPYRP              SEQ ID NO:717
IEYLVSFGVWIRTPPPYRPP             SEQ ID NO:718
VIEYLVSFGVWIRTPPPY               SEQ ID NO:719
VIEYLVSFGVWIRTPPPYR              SEQ ID NO:720
VIEYLVSFGVWIRTPPPYRP             SEQ ID NO:721
TVIEYLVSFGVWIRTPPPY              SEQ ID NO:722
TVIEYLVSFGVWIRTPPPYR             SEQ ID NO:723
DTVIEYLVSFGVWIRTPPPY             SEQ ID NO:724

[0116]

TABLE 7
PPPY Motif Containing Peptides from Human
Herpesvirus 4 (Epstein-Barr Virus)
Latent Membrane Protein 2A
(GenBank Accession No. CAA57375)
PPPY                  EDPY       SEQ ID NO:725
PPPY                  EDPYW      SEQ ID NO:726
PPPY                  EDPYWG     SEQ ID NO:727
PPPY                  EDPYWGN    SEQ ID NO:728
PPPY                  EDPYWGNG   SEQ ID NO:729
PPPY                  EDPYWGNGD  SEQ ID NO:730
PPPY                  EDPYWGNGDR SEQ ID NO:731
PPPY                  EDPYWGNGDRH SEQ ID NO:732
PPPY                  EDPYWGNGDRHS SEQ ID NO:733
PPPY                  EDPYWGNGDRHSD SEQ ID NO:734
PPPY                  EDPYWGNGDRHSDY SEQ ID NO:735
PPPY                  EDPYWGNGDRHSDYQ SEQ ID NO:736
PPPY                  EDPYWGNGDRHSDYQP SEQ ID NO:737
PPPPYEDP                         SEQ ID NO:738
PPPPYEDPY                        SEQ ID NO:739
PPPPYEDPYW                       SEQ ID NO:740
PPPPYEDPYWG                      SEQ ID NO:741
PPPPYEDPYWGN                     SEQ ID NO:742
PPPPYEDPYWGNG                    SEQ ID NO:743
PPPPYEDPYWGNGD                   SEQ ID NO:744
PPPPYEDPYWGNGDR                  SEQ ID NO:745
PPPPYEDPYWGNGDRH                 SEQ ID NO:746
PPPPYEDPYWGNGDRHS                SEQ ID NO:747
PPPPYEDPYWGNGDRHSD               SEQ ID NO:748
PPPPYEDPYWGNGDRHSDY              SEQ ID NO:749
PPPPYEDPYWGNGDRHSDYQ             SEQ ID NO:750
EPPPPYED                         SEQ ID NO:751
EPPPPYEDP                        SEQ ID NO:752
EPPPPYEDPY                       SEQ ID NO:753
EPPPPYEDPYW                      SEQ ID NO:754
EPPPPYEDPYWG                     SEQ ID NO:755
EPPPPYEDPYWGN                    SEQ ID NO:756
EPPPPYEDPYWGNG                   SEQ ID NO:757
EPPPPYEDPYWGNGD                  SEQ ID NO:758
EPPPPYEDPYWGNGDR                 SEQ ID NO:759
EPPPPYEDPYWGNGDRH                SEQ ID NO:760
EPPPPYEDPYWGNGDRHS               SEQ ID NO:761
EPPPPYEDPYWGNGDRHSD              SEQ ID NO:762
EPPPPYEDPYWGNGDRHSDY             SEQ ID NO:763
EEPPPPYE                         SEQ ID NO:764
EEPPPPYED                        SEQ ID NO:765
EEPPPPYEDP                       SEQ ID NO:766
EEPPPPYEDPY                      SEQ ID NO:767
EEPPPPYEDPYW                     SEQ ID NO:768
EEPPPPYEDPYWG                    SEQ ID NO:769
EEPPPPYEDPYWGN                   SEQ ID NO:770
EEPPPPYEDPYWGNG                  SEQ ID NO:771
EEPPPPYEDPYWGNGD                 SEQ ID NO:772
EEPPPPYEDPYWGNGDR                SEQ ID NO:773
EEPPPPYEDPYWGNGDRH               SEQ ID NO:774
EEPPPPYEDPYWGNGDRHS              SEQ ID NO:775
EEPPPPYEDPYWGNGDRHSD             SEQ ID NO:776
NEEPPPPY                         SEQ ID NO:777
NEEPPPPYE                        SEQ ID NO:778
NEEPPPPYED                       SEQ ID NO:779
NEEPPPPYEDP                      SEQ ID NO:780
NEEPPPPYEDPY                     SEQ ID NO:781
NEEPPPPYEDPYW                    SEQ ID NO:782
NEEPPPPYEDPYWG                   SEQ ID NO:783
NEEPPPPYEDPYWGN                  SEQ ID NO:784
NEEPPPPYEDPYWGNG                 SEQ ID NO:785
NEEPPPPYEDPYWGNGD                SEQ ID NO:786
NEEPPPPYEDPYWGNGDR               SEQ ID NO:787
NEEPPPPYEDPYWGNGDRH              SEQ ID NO:788
NEEPPPPYEDPYWGNGDRHS             SEQ ID NO:789
SNEEPPPPY                        SEQ ID NO:790
SNEEPPPPYE                       SEQ ID NO:791
SNEEPPPPYED                      SEQ ID NO:792
SNEEPPPPYEDP                     SEQ ID NO:793
SNEEPPPPYEDPY                    SEQ ID NO:794
SNEEPPPPYEDPYW                   SEQ ID NO:795
SNEEPPPPYEDPYWG                  SEQ ID NO:796
SNEEPPPPYEDPYWGN                 SEQ ID NO:797
SNEEPPPPYEDPYWGNG                SEQ ID NO:798
SNEEPPPPYEDPYWGNGD               SEQ ID NO:799
SNEEPPPPYEDPYWGNGDR              SEQ ID NO:800
SNEEPPPPYEDPYWGNGDRH             SEQ ID NO:801
ESNEEPPPPY                       SEQ ID NO:802
ESNEEPPPPYE                      SEQ ID NO:803
ESNEEPPPPYED                     SEQ ID NO:804
ESNEEPPPPYEDP                    SEQ ID NO:805
ESNEEPPPPYEDPY                   SEQ ID NO:806
ESNEEPPPPYEDPYW                  SEQ ID NO:807
ESNEEPPPPYEDPYWG                 SEQ ID NO:808
ESNEEPPPPYEDPYWGN                SEQ ID NO:809
ESNEEPPPPYEDPYWGNG               SEQ ID NO:810
ESNEEPPPPYEDPYWGNGD              SEQ ID NO:811
SNEEPPPPYEDPYWGNGDR              SEQ ID NO:812
RESNEEPPPPY                      SEQ ID NO:813
RESNEEPPPPYE                     SEQ ID NO:814
RESNEEPPPPYED                    SEQ ID NO:815
RESNEEPPPPYEDP                   SEQ ID NO:816
RESNEEPPPPYEDPY                  SEQ ID NO:817
RESNEEPPPPYEDPYW                 SEQ ID NO:818
RESNEEPPPPYEDPYWG                SEQ ID NO:819
RESNEEPPPPYEDPYWGN               SEQ ID NO:820
RESNEEPPPPYEDPYWGNG              SEQ ID NO:821
RESNEEPPPPYEDPYWGNGD             SEQ ID NO:822
ERESNEEPPPPY                     SEQ ID NO:823
ERESNEEPPPPYE                    SEQ ID NO:824
ERESNEEPPPPYED                   SEQ ID NO:825
ERESNEEPPPPYEDP                  SEQ ID NO:826
ERESNEEPPPPYEDPY                 SEQ ID NO:827
ERESNEEPPPPYEDPYW                SEQ ID NO:828
ERESNEEPPPPYEDPYWG               SEQ ID NO:829
ERESNEEPPPPYEDPYWGN              SEQ ID NO:830
ERESNEEPPPPYEDPYWGNG             SEQ ID NO:831
EERESNEEPPPPY                    SEQ ID NO:832
EERESNEEPPPPYE                   SEQ ID NO:833
EERESNEEPPPPYED                  SEQ ID NO:834
EERESNEEPPPPYEDP                 SEQ ID NO:835
EERESNEEPPPPYEDPY                SEQ ID NO:836
EERESNEEPPPPYEDPYW               SEQ ID NO:837
EERESNEEPPPPYEDPYWG              SEQ ID NO:838
EERESNEEPPPPYEDPYWGN             SEQ ID NO:839
DEERESNEEPPPPY                   SEQ ID NO:840
DEERESNEEPPPPYE                  SEQ ID NO:841
DEERESNEEPPPPYED                 SEQ ID NO:842
DEERESNEEPPPPYEDP                SEQ ID NO:843
DEERESNEEPPPPYEDPY               SEQ ID NO:844
DEERESNEEPPPPYEDPYW              SEQ ID NO:845
DEERESNEEPPPPYEDPYWG             SEQ ID NO:846
NDEERESNEEPPPPY                  SEQ ID NO:847
NDEERESNEEPPPPYE                 SEQ ID NO:848
NDEERESNEEPPPPYED                SEQ ID NO:849
NDEERESNEEPPPPYEDP               SEQ ID NO:850
NDEERESNEEPPPPYEDPY              SEQ ID NO:851
NDEERESNEEPPPPYEDPYW             SEQ ID NO:852
PNDEERESNEEPPPPY                 SEQ ID NO:853
PNDEERESNEEPPPPYE                SEQ ID NO:854
PNDEERESNEEPPPPYED               SEQ ID NO:855
PNDEERESNEEPPPPYEDP              SEQ ID NO:856
PNDEERESNEEPPPPYEDPY             SEQ ID NO:857
PPNDEERESNEEPPPPY                SEQ ID NO:858
PPNDEERESNEEPPPPYE               SEQ ID NO:859
PPNDEERESNEEPPPPYED              SEQ ID NO:860
PPNDEERESNEEPPPPYEDP             SEQ ID NO:861
TPPNDEERESNEEPPPPY               SEQ ID NO:862
TPPNDEERESNEEPPPPYE              SEQ ID NO:863
TPPNDEERESNEEPPPPYED             SEQ ID NO:864
PTPPNDEERESNEEPPPPY              SEQ ID NO:865
PTPPNDEERESNEEPPPPYE             SEQ ID NO:866
TPTPPNDEERESNEEPPPPY             SEQ ID NO:867
PPPY                  SPRD       SEQ ID NO:868
PPPY                  SPRDD      SEQ ID NO:869
PPPY                  SPRDDS     SEQ ID NO:870
PPPY                  SPRDDSS    SEQ ID NO:871
PPPY                  SPRDDSSQ   SEQ ID NO:872
PPPY                  SPRDDSSQH  SEQ ID NO:873
PPPY                  SPRDDSSQHI SEQ ID NO:874
PPPY                  SPRDDSSQHIY SEQ ID NO:875
PPPY                  SPRDDSSQHIYE SEQ ID NO:876
PPPY                  SPRDDSSQHIYEE SEQ ID NO:877
PPPY                  SPRDDSSQHIYEEA SEQ ID NO:878
PPPY                  SPRDDSSQHIYEEAD SEQ ID NO:879
PPPY                  SPRDDSSQHIYEEADR SEQ ID NO:880
PPPPYSPR                         SEQ ID NO:881
PPPPYSPRD                        SEQ ID NO:882
PPPPYSPRDD                       SEQ ID NO:883
PPPPYSPRDDS                      SEQ ID NO:884
PPPPYSPRDDSS                     SEQ ID NO:885
PPPPYSPRDDSSQ                    SEQ ID NO:886
PPPPYSPRDDSSQH                   SEQ ID NO:887
PPPPYSPRDDSSQHI                  SEQ ID NO:888
PPPPYSPRDDSSQHIY                 SEQ ID NO:889
PPPPYSPRDDSSQHIYE                SEQ ID NO:890
PPPPYSPRDDSSQHIYEE               SEQ ID NO:891
PPPPYSPRDDSSQHIYEEA              SEQ ID NO:892
PPPPYSPRDDSSQHIYEEAD             SEQ ID NO:893
LPPPPYSP                         SEQ ID NO:894
LPPPPYSPR                        SEQ ID NO:895
LPPPPYSPRD                       SEQ ID NO:896
LPPPPYSPRDD                      SEQ ID NO:897
LPPPPYSPRDDS                     SEQ ID NO:898
LPPPPYSPRDDSS                    SEQ ID NO:899
LPPPPYSPRDDSSQ                   SEQ ID NO:900
LPPPPYSPRDDSSQH                  SEQ ID NO:901
LPPPPYSPRDDSSQHI                 SEQ ID NO:902
LPPPPYSPRDDSSQHIY                SEQ ID NO:903
LPPPPYSPRDDSSQHIYE               SEQ ID NO:904
LPPPPYSPRDDSSQHIYEE              SEQ ID NO:905
LPPPPYSPRDDSSQHIYEEA             SEQ ID NO:906
GLPPPPYS                         SEQ ID NO:907
GLPPPPYSP                        SEQ ID NO:908
GLPPPPYSPR                       SEQ ID NO:909
GLPPPPYSPRD                      SEQ ID NO:910
GLPPPPYSPRDD                     SEQ ID NO:911
GLPPPPYSPRDDS                    SEQ ID NO:912
GLPPPPYSPRDDSS                   SEQ ID NO:913
GLPPPPYSPRDDSSQ                  SEQ ID NO:914
GLPPPPYSPRDDSSQH                 SEQ ID NO:915
GLPPPPYSPRDDSSQHI                SEQ ID NO:916
LPPPPYSPRDDSSQHIY                SEQ ID NO:917
GLPPPPYSPRDDSSQHIYE              SEQ ID NO:918
GLPPPPYSPRDDSSQHIYEE             SEQ ID NO:919
DGLPPPPY                         SEQ ID NO:920
DGLPPPPYS                        SEQ ID NO:921
DGLPPPPYSP                       SEQ ID NO:922
DGLPPPPYSPR                      SEQ ID NO:923
DGLPPPPYSPRD                     SEQ ID NO:924
DGLPPPPYSPRDD                    SEQ ID NO:925
DGLPPPPYSPRDDS                   SEQ ID NO:926
DGLPPPPYSPRDDSS                  SEQ ID NO:927
DGLPPPPYSPRDDSSQ                 SEQ ID NO:928
DGLPPPPYSPRDDSSQH                SEQ ID NO:929
DGLPPPPYSPRDDSSQHI               SEQ ID NO:930
DGLPPPPYSPRDDSSQHIY              SEQ ID NO:931
DGLPPPPYSPRDDSSQHIYE             SEQ ID NO:932
NDGLPPPPY                        SEQ ID NO:933
NDGLPPPPYS                       SEQ ID NO:934
NDGLPPPPYSP                      SEQ ID NO:935
NDGLPPPPYSPR                     SEQ ID NO:936
NDGLPPPPYSPRD                    SEQ ID NO:937
NDGLPPPPYSPRDD                   SEQ ID NO:938
NDGLPPPPYSPRDDS                  SEQ ID NO:939
NDGLPPPPYSPRDDSS                 SEQ ID NO:940
NDGLPPPPYSPRDDSSQ                SEQ ID NO:941
NDGLPPPPYSPRDDSSQH               SEQ ID NO:942
NDGLPPPPYSPRDDSSQHI              SEQ ID NO:943
NDGLPPPPYSPRDDSSQHIY             SEQ ID NO:944
GNDGLPPPPY                       SEQ ID NO:945
GNDGLPPPPYS                      SEQ ID NO:946
GNDGLPPPPYSP                     SEQ ID NO:947
GNDGLPPPPYSPR                    SEQ ID NO:948
GNDGLPPPPYSPRD                   SEQ ID NO:949
GNDGLPPPPYSPRDD                  SEQ ID NO:950
GNDGLPPPPYSPRDDS                 SEQ ID NO:951
GNDGLPPPPYSPRDDSS                SEQ ID NO:952
GNDGLPPPPYSPRDDSSQ               SEQ ID NO:953
GNDGLPPPPYSPRDDSSQH              SEQ ID NO:954
GNPGLPPPPYSPRDDSSQHI             SEQ ID NO:955
DGNDGLPPPPY                      SEQ ID NO:956
DGNDGLPPPPYS                     SEQ ID NO:957
DGNDGLPPPPYSP                    SEQ ID NO:958
DGNDGLPPPPYSPR                   SEQ ID NO:959
DGNDGLPPPPYSPRD                  SEQ ID NO:960
DGNDGLPPPPYSPRDD                 SEQ ID NO:961
DGNDGLPPPPYSPRDDS                SEQ ID NO:962
DGNDGLPPPPYSPRDDSS               SEQ ID NO:963
DGNDGLPPPPYSPRDDSSQ              SEQ ID NO:964
DGNDGLPPPPYSPRDDSSQH             SEQ ID NO:965
HDGNDGLPPPPY                     SEQ ID NO:966
HDGNDGLPPPPYS                    SEQ ID NO:967
HDGNDGLPPPPYSP                   SEQ ID NO:968
HDGNDGLPPPPYSPR                  SEQ ID NO:969
HDGNDGLPPPPYSPRD                 SEQ ID NO:970
HDGNDGLPPPPYSPRDD                SEQ ID NO:971
HDGNDGLPPPPYSPRDDS               SEQ ID NO:972
HDGNDGLPPPPYSPRDDSS              SEQ ID NO:973
HDGNDGLPPPPYSPRDDSSQ             SEQ ID NO:974
QHDGNDGLPPPPY                    SEQ ID NO:975
QHDGNDGLPPPPYS                   SEQ ID NO:976
QHDGNDGLPPPPYSP                  SEQ ID NO:977
QHDGNDGLPPPPYSPR                 SEQ ID NO:978
QHDGNDGLPPPPYSPRD                SEQ ID NO:979
QHDGNDGLPPPPYSPRDD               SEQ ID NO:980
QHDGNDGLPPPPYSPRDDS              SEQ ID NO:981
QHDGNDGLPPPPYSPRDDSS             SEQ ID NO:982
LQHDGNDGLPPPPY                   SEQ ID NO:983
LQHDGNDGLPPPPYS                  SEQ ID NO:984
LQHDGNDGLPPPPYSP                 SEQ ID NO:985
LQHDGNDGLPPPPYSPR                SEQ ID NO:986
LQHDGNDGLPPPPYSPRD               SEQ ID NO:987
LQHDGNDGLPPPPYSPRDD              SEQ ID NO:988
LQHIDGNDGLPPPPYSPRDDS            SEQ ID NO:989
GLQHDGNPGLPPPPY                  SEQ ID NO:990
GLQHDGNDGLPPPPYS                 SEQ ID NO:991
GLQHDGNDGLPPPPYSP                SEQ ID NO:992
GLQHDGNDGLPPPPYSPR               SEQ ID NO:993
GLQHDGNDGLPPPPYSPRD              SEQ ID NO:994
GLQHDGNDGLPPPPYSPRDD             SEQ ID NO:995
LGLQHDGNDGLPPPPY                 SEQ ID NO:996
LGLQHDGNDGLPPPPYS                SEQ ID NO:997
LGLQHDGNDGLPPPPYSP               SEQ ID NO:998
LGLQHDGNDGLPPPPYSPR              SEQ ID NO:999
LGLQHDGNDGLPPPPYSPRD             SEQ ID NO:1000
YLGLQHDGNDGLPPPPY                SEQ ID NO:1001
YLGLQHDGNDGLPPPPYS               SEQ ID NO:1002
YLGLQHDGNDGLPPPPYSP              SEQ ID NO:1003
YLGLQHDGNDGLPPPPYSPR             SEQ ID NO:1004
LYLGLQHDGNDGLPPPPY               SEQ ID NO:1005
LYLGLQHDGNDGLPPPPYS              SEQ ID NO:1006
LYLGLQHDGNDGLPPPPYSP             SEQ ID NO:1007
SLYLGLQHDGNDGLPPPPY              SEQ ID NO:1008
SLYLGLQHDGNDGLPPPPYS             SEQ ID NO:1009
PSLYLGLQHDGNDGLPPPPY             SEQ ID NO:1010

[0117]

TABLE 8
PPXY Motif Containing Peptides from Human
Herpesvirus 1 (Strain F) UL56 Protein
(GenBank Accession No. A43965)
PPPY                  DSLS       SEQ ID NO:1011
PPPY                  DSLSG      SEQ ID NO:1012
PPPY                  DSLSGR     SEQ ID NO:1013
PPPY                  DSLSGRN    SEQ ID NO:1014
PPPY                  DSLSGRNE   SEQ ID NO:1015
PPPY                  DSLSGRNEG  SEQ ID NO:1016
PPPY                  DSLSGRNEGP SEQ ID NO:1017
PPPY                  DSLSGRNEGPF SEQ ID NO:1018
PPPY                  DSLSGRNEGPFV SEQ ID NO:1019
PPPY                  DSLSGRNEGPFVV SEQ ID NO:1020
PPPY                  DSLSGRNEGPFVVI SEQ ID NO:1021
PPPY                  DSLSGRNEGPFVVID SEQ ID NO:1022
PPPY                  DSLSGRNEGPFVVIDL SEQ ID NO:1023
PPPPYDSL                         SEQ ID NO:1O24
PPPPYDSLS                        SEQ ID NO:1025
PPPPYDSLSG                       SEQ ID NO:1026
PPPPYDSLSGR                      SEQ ID NO:1027
PPPPYDSLSGRN                     SEQ ID NO:1028
PPPPYDSLSGRNE                    SEQ ID NO:1029
PPPPYDSLSGRNEG                   SEQ ID NO:1030
PPPPYDSLSGRNEGP                  SEQ ID NO:1031
PPPPYDSLSGRNEGPF                 SEQ ID NO:1032
PPPPYDSLSGRNEGPFV                SEQ ID NO:1033
PPPPYDSLSGRNEGPFVV               SEQ ID NO:1034
PPPPYDSLSGRNEGPFVVI              SEQ ID NO:1035
PPPPYDSLSGRNEGPFVVID             SEQ ID NO:1036
DPPPPYDS                         SEQ ID NO:1037
DPPPPYDSL                        SEQ ID NO:1038
DPPPPYDSLS                       SEQ ID NO:1039
DPPPPYDSLSG                      SEQ ID NO:1040
DPPPPYDSLSGR                     SEQ ID NO:1041
DPPPPYDSLSGRN                    SEQ ID NO:1042
DPPPPYDSLSGRNE                   SEQ ID NO:1043
DPPPPYDSLSGRNEG                  SEQ ID NO:1044
DPPPPYDSLSGRNEGP                 SEQ ID NO:1045
DPPPPYDSLSGRNEGPF                SEQ ID NO:1046
DPPPPYDSLSGRNEGPFV               SEQ ID NO:1047
DPPPPYDSLSGRNEGPFVV              SEQ ID NO:1048
DPPPPYDSLSGRNEGPFVVI             SEQ ID NO:1049
ADPPPPYD                         SEQ ID NO:1050
ADPPPPYDS                        SEQ ID NO:1051
ADPPPPYDSL                       SEQ ID NO:1052
ADPPPPYDSLS                      SEQ ID NO:1053
ADPPPPYDSLSG                     SEQ ID NO:1054
ADPPPPYDSLSGR                    SEQ ID NO:1055
ADPPPPYDSLSGRN                   SEQ ID NO:1056
ADPPPPYDSLSGRNE                  SEQ ID NO:1057
ADPPPPYDSLSGRNEG                 SEQ ID NO:1058
ADPPPPYDSLSGRNEGP                SEQ ID NO:1059
ADPPPPYDSLSGRNEGPF               SEQ ID NO:1060
ADPPPPYDSLSGRNEGPFV              SEQ ID NO:1061
ADPPPPYDSLSGRNEGPFVV             SEQ ID NO:1062
FADPPPPY                         SEQ ID NO:1063
FADPPPPYD                        SEQ ID NO:1064
FADPPPPYDS                       SEQ ID NO:1065
FADPPPPYDSL                      SEQ ID NO:1066
FADPPPPYDSLS                     SEQ ID NO:1067
FADPPPPYDSLSG                    SEQ ID NO:1068
FADPPPPYDSLSGR                   SEQ ID NO:1069
FADPPPPYDSLSGRN                  SEQ ID NO:1070
FADPPPPYDSLSGRNE                 SEQ ID NO:1071
FADPPPPYDSLSGRNEG                SEQ ID NO:1072
FADPPPPYDSLSGRNEGP               SEQ ID NO:1073
FADPPPPYDSLSGRNEGPF              SEQ ID NO:1074
FADPPPPYDSLSGRNEGPFV             SEQ ID NO:1075
AFADPPPPY                        SEQ ID NO:1076
AFADPPPPYD                       SEQ ID NO:1077
AFADPPPPYDS                      SEQ ID NO:1078
AFADPPPPYDSL                     SEQ ID NO:1079
AFADPPPPYDSLS                    SEQ ID NO:1080
AFADPPPPYDSLSG                   SEQ ID NO:1081
AFADPPPPYDSLSGR                  SEQ ID NO:1082
AFADPPPPYDSLSGRN                 SEQ ID NO:1083
AFADPPPPYDSLSGRNE                SEQ ID NO:1084
AFADPPPPYDSLSGRNEG               SEQ ID NO:1085
AFADPPPPYDSLSGRNEGP              SEQ ID NO:1086
AFADPPPPYDSLSGRNEGPF             SEQ ID NO:1087
NAFADPPPPY                       SEQ ID NO:1088
NAFADPPPPYD                      SEQ ID NO:1089
NAFADPPPPYDS                     SEQ ID NO:1090
NAFADPPPPYDSL                    SEQ ID NO:1091
NAFADPPPPYDSLS                   SEQ ID NO:1092
NAFADPPPPYDSLSG                  SEQ ID NO:1093
NAFADPPPPYDSLSGR                 SEQ ID NO:1094
NAFADPPPPYDSLSGRN                SEQ ID NO:1095
NAFADPPPPYDSLSGRNE               SEQ ID NO:1096
NAFADPPPPYDSLSGRNEG              SEQ ID NO:1097
NAFADPPPPYDSLSGRNEGP             SEQ ID NO:1098
GNAFADPPPPY                      SEQ ID NO:1099
GNAFADPPPPYD                     SEQ ID NO:1100
GNAFADPPPPYDS                    SEQ ID NO:1101
GNAFADPPPPYDSL                   SEQ ID NO:1102
GNAFADPPPPYDSLS                  SEQ ID NO:1103
GNAFADPPPPYDSLSG                 SEQ ID NO:1104
GNAFADPPPPYDSLSGR                SEQ ID NO:1105
GNAFADPPPPYDSLSGRN               SEQ ID NO:1106
GNAFADPPPPYDSLSGRNE              SEQ ID NO:1107
GNAFADPPPPYDSLSGRNEG             SEQ ID NO:1108
AGNAFADPPPPY                     SEQ ID NO:1109
AGNAFADPPPPYD                    SEQ ID NO:1110
AGNAFADPPPPYDS                   SEQ ID NO:1111
AGNAFADPPPPYDSL                  SEQ ID NO:1112
AGNAFADPPPPYDSLS                 SEQ ID NO:1113
AGNAFADPPPPYDSLSG                SEQ ID NO:1114
AGNAFADPPPPYDSLSGR               SEQ ID NO:1115
AGNAFADPPPPYDSLSGRN              SEQ ID NO:1116
AGNAFADPPPPYDSLSGRNE             SEQ ID NO:1117
SAGNAFADPPPPY                    SEQ ID NO:1118
SAGNAFADPPPPYD                   SEQ ID NO:1119
SAGNAFADPPPPYDS                  SEQ ID NO:1120
SAGNAFADPPPPYDSL                 SEQ ID NO:1121
SAGNAFADPPPPYDSLS                SEQ ID NO:1122
SAGNAFADPPPPYDSLSG               SEQ ID NO:1123
SAGNAFADPPPPYDSLSGR              SEQ ID NO:1124
SAGNAFADPPPPYDSLSGRN             SEQ ID NO:1125
WSAGNAFADPPPPY                   SEQ ID NO:1126
WSAGNAFADPPPPYD                  SEQ ID NO:1127
WSAGNAFADPPPPYDS                 SEQ ID NO:1128
WSAGNAFADPPPPYDSL                SEQ ID NO:1129
WSAGNAFADPPPPYDSLS               SEQ ID NO:1130
WSAGNAFADPPPPYDSLSG              SEQ ID NO:1131
WSAGNAFADPPPPYDSLSGR             SEQ ID NO:1132
LWSAGNAFADPPPPY                  SEQ ID NO:1133
LWSAGNAFADPPPPYD                 SEQ ID NO:1134
LWSAGNAFADPPPPYDS                SEQ ID NO:1135
LWSAGNAFADPPPPYDSL               SEQ ID NO:1136
LWSAGNAFADPPPPYDSLS              SEQ ID NO:1137
LWSAGNAFADPPPPYDSLSG             SEQ ID NO:1138
GLWSAGNAFADPPPPY                 SEQ ID NO:1139
GLWSAGNAFADPPPPYD                SEQ ID NO:1140
GLWSAGNAFADPPPPYDS               SEQ ID NO:1141
GLWSAGNAFADPPPPYDSL              SEQ ID NO:1142
GLWSAGNAFADPPPPYDSLS             SEQ ID NO:1143
AGLWSAGNAFADPPPPY                SEQ ID NO:1144
AGLWSAGNAFADPPPPYD               SEQ ID NO:1145
AGLWSAGNAFADPPPPYDS              SEQ ID NO:1146
AGLWSAGNAFADPPPPYDSL             SEQ ID NO:1147
DAGLWSAGNAFADPPPPY               SEQ ID NO:1148
DAGLWSAGNAFADPPPPYD              SEQ ID NO:1149
DAGLWSAGNAFADPPPPYDS             SEQ ID NO:1150
PDAGLWSAGNAPADPPPPY              SEQ ID NO:1151
PDAGLWSAGNAFADPPPPYD             SEQ ID NO:1152
QPDAGLWSAGNAFADPPPPY             SEQ ID NO:1153
PPPY                  SAGP       SEQ ID NO:1154
PPPY                  SAGPL      SEQ ID NO:1155
PPPY                  SAGPLL     SEQ ID NO:1156
PPPY                  SAGPLLS    SEQ ID NO:1157
PPPY                  SAGPLLSV   SEQ ID NO:1158
PPPY                  SAGPLLSVP  SEQ ID NO:1159
PPPY                  SAGPLLSVPI SEQ ID NO:1160
PPPY                  SAGPLLSVPIP SEQ ID NO:1161
PPPY                  SAGPLLSVPIPP SEQ ID NO:1162
PPPY                  SAGPLLSVPIPPT SEQ ID NO:1163
PPPY                  SAGPLLSVPIPPTS SEQ ID NO:1164
PPPY                  SAGPLLSVPIPPTSS SEQ ID NO:1165
PPPY                  SAGPLLSVPIIPPTSSG SEQ ID NO:1166
PPPPYSAG                         SEQ ID NO:1167
PPPPYSAGP                        SEQ ID NO:1168
PPPPYSAGPL                       SEQ ID NO:1169
PPPPYSAGPLL                      SEQ ID NO:1170
PPPPYSAGPLLS                     SEQ ID NO:1171
PPPPYSAGPLLSV                    SEQ ID NO:1172
PPPPYSAGPLLSVP                   SEQ ID NO:1173
PPPPYSAGPLLSVPI                  SEQ ID NO:1174
PPPPYSAGPLLSVPIP                 SEQ ID NO:1175
PPPPYSAGPLLSVPIPP                SEQ ID NO:1176
PPPPYSAGPLLSVPIPPT               SEQ ID NO:1177
PPPPYSAGPLLSVPIPPTS              SEQ ID NO:1178
PPPPYSAGPLLSVPIPPTSS             SEQ ID NO:1179
DPPPPYSA                         SEQ ID NO:1180
DPPPPYSAG                        SEQ ID NO:1181
DPPPPYSAGP                       SEQ ID NO:1182
DPPPPYSAGPL                      SEQ ID NO:1183
DPPPPYSAGPLL                     SEQ ID NO:1184
DPPPPYSAGPLLS                    SEQ ID NO:1185
DPPPPYSAGPLLSV                   SEQ ID NO:1186
DPPPPYSAGPLLSVP                  SEQ ID NO:1187
DPPPPYSAGPLLSVPI                 SEQ ID NO:1188
DPPPPYSAGPLLSVPIP                SEQ ID NO:1189
DPPPPYSAGPLLSVPIPP               SEQ ID NO:1190
DPPPPYSAGPLLSVPIPPT              SEQ ID NO:1191
DPPPPYSAGPLLSVPIPPTS             SEQ ID NO:1192
TDPPPPYS                         SEQ ID NO:1193
TDPPPPYSA                        SEQ ID NO:1194
TDPPPPYSAG                       SEQ ID NO:1195
TDPPPPYSAGP                      SEQ ID NO:1196
TDPPPPYSAGPL                     SEQ ID NO:1197
TDPPPPYSAGPLL                    SEQ ID NO:1198
TDPPPPYSAGPLLS                   SEQ ID NO:1199
TDPPPPYSAGPLLSV                  SEQ ID NO:1200
TDPPPPYSAGPLLSVP                 SEQ ID NO:1201
TDPPPPYSAGPLLSVPI                SEQ ID NO:1202
TDPPPPYSAGPLLSVPIP               SEQ ID NO:1203
TDPPPPYSAGPLLSVPIPP              SEQ ID NO:1204
TDPPPPYSAGPLLSVPIIPPT            SEQ ID NO:1205
PTDPPPPY                         SEQ ID NO:1206
PTDPPPPYS                        SEQ ID NO:1207
PTDPPPPYSA                       SEQ ID NO:1208
PTDPPPPYSAG                      SEQ ID NO:1209
PTDPPPPYSAGP                     SEQ ID NO:1210
PTDPPPPYSAGPL                    SEQ ID NO:1211
PTDPPPPYSAGPLL                   SEQ ID NO:1212
PTDPPPPYSAGPLLS                  SEQ ID NO:1213
PTDPPPPYSAGPLLSV                 SEQ ID NO:1214
PTDPPPPYSAGPLLSVP                SEQ ID NO:1215
PTDPPPPYSAGPLLSVPI               SEQ ID NO:1216
PTDPPPPYSAGPLLSVPIP              SEQ ID NO:1217
PTDPPPPYSAGPLLSVPTPP             SEQ ID NO:1218
TPTDPPPPY                        SEQ ID NO:1219
TPTDPPPPYS                       SEQ ID NO:1220
TPTDPPPPYSA                      SEQ ID NO:1221
TPTDPPPPYSAG                     SEQ ID NO:1222
TPTDPPPPYSAGP                    SEQ ID NO:1223
TPTDPPPPYSAGPL                   SEQ ID NO:1224
TPTDPPPPYSAGPLL                  SEQ ID NO:1225
TPTDPPPPYSAGPLLS                 SEQ ID NO:1226
TPTDPPPPYSAGPLLSV                SEQ ID NO:1227
TPTDPPPPYSAGPLLSVP               SEQ ID NO:1228
TPTDPPPPYSAGPLLSVPI              SEQ ID NO:1229
TPTDPPPPYSAGPLLSVPIP             SEQ ID NO:1230
DTPTDPPPPY                       SEQ ID NO:1231
DTPTDPPPPYS                      SEQ ID NO:1232
DTPTDPPPPYSA                     SEQ ID NO:1233
DTPTDPPPPYSAG                    SEQ ID NO:1234
DTPTDPPPPYSAGP                   SEQ ID NO:1235
DTPTDPPPPYSAGPL                  SEQ ID NO:1236
DTPTDPPPPYSAGPLL                 SEQ ID NO:1237
DTPTDPPPPYSAGPLLS                SEQ ID NO:1238
DTPTDPPPPYSAGPLLSV               SEQ ID NO:1239
DTPTDPPPPYSAGPLLSVP              SEQ ID NO:1240
DTPTDPPPPYSAGPLLSVPI             SEQ ID NO:1241
LDTPTDPPPPY                      SEQ ID NO:1242
LDTPTDPPPPYS                     SEQ ID NO:1243
LDTPTDPPPPYSA                    SEQ ID NO:1244
LDTPTDPPPPYSAG                   SEQ ID NO:1245
LDTPTDPPPPYSAGP                  SEQ ID NO:1246
LDTPTDPPPPYSAGPL                 SEQ ID NO:1247
LDTPTDPPPPYSAGPLL                SEQ ID NO:1248
LDTPTDPPPPYSAGPLLS               SEQ ID NO:1249
LDTPTDPPPPYSAGPLLSV              SEQ ID NO:1250
LDTPTDPPPPYSAGPLLSVP             SEQ ID NO:1251
DLDTPTDPPPPY                     SEQ ID NO:1252
DLDTPTDPPPPYS                    SEQ ID NO:1253
DLDTPTDPPPPYSA                   SEQ ID NO:1254
DLDTPTDPPPPYSAG                  SEQ ID NO:1255
DLDTPTDPPPPYSAGP                 SEQ ID NO:1256
DLDTPTDPPPPYSAGPL                SEQ ID NO:1257
DLDTPTDPPPPYSAGPLL               SEQ ID NO:1258
DLDTPTDPPPPYSAGPLLS              SEQ ID NO:1259
DLDTPTDPPPPYSAGPLLSV             SEQ ID NO:1260
IDLDTPTDPPPPY                    SEQ ID NO:1261
IDLDTPTDPPPPYS                   SEQ ID NO:1262
IDLDTPTDPPPPYSA                  SEQ ID NO:1263
IDLDTPTDPPPPYSAG                 SEQ ID NO:1264
IDLDTPTDPPPPYSAGP                SEQ ID NO:1265
IDLDTPTDPPPPYSAGPL               SEQ ID NO:1266
IDLDTPTDPPPPYSAGPLL              SEQ ID NO:1267
LDLDTPTDPPPPYSAGPLLS             SEQ ID NO:1268
VIDLDTPTDPPPPY                   SEQ ID NO:1269
VIDLDTPTDPPPPYS                  SEQ ID NO:1270
VIDLDTPTDPPPPYSA                 SEQ ID NO:1271
VIDLDTPTDPPPPYSAG                SEQ ID NO:1272
VIDLDTPTDPPPPYSAGP               SEQ ID NO:1273
VIDLDTPTDPPPPYSAGPL              SEQ ID NO:1274
VIDLDTPTDPPPPYSAGPLL             SEQ ID NO:1275
VVIDLDTPTDPPPPY                  SEQ ID NO:1276
VVIDLDTPTDPPPPYS                 SEQ ID NO:1277
VVIDLDTPTDPPPPYSA                SEQ ID NO:1278
VVIDLDTPTDPPPPYSAG               SEQ ID NO:1279
VVIDLDTPTDPPPPYSAGP              SEQ ID NO:1280
VVIDLDTPTDPPPPYSAGPL             SEQ ID NO:1281
FVVIDLDTPTDPPPPY                 SEQ ID NO:1282
FVVIDLDTPTDPPPPYS                SEQ ID NO:1283
FVVIDLDTPTDPPPPYSA               SEQ ID NO:1284
FVVIDLDTPTDPPPPYSAG              SEQ ID NO:1285
FVVIDLDTPTDPPPPYSAGP             SEQ ID NO:1286
PFVVIDLDTPTDPPPPY                SEQ ID NO:1287
PFVVIDLDTPTDPPPPYS               SEQ ID NO:1288
PFVVIDLDTPTDPPPPYSA              SEQ ID NO:1289
PFVVIDLDTPTDPPPPYSAG             SEQ ID NO:1290
GPFVVIDLDTPTDPPPPY               SEQ ID NO:1291
GPFVVIDLDTPTDPPPPYS              SEQ ID NO:1292
GPFVVIDLDTPTDPPPPYSA             SEQ ID NO:1293
EGPFVVIDLDTPTDPPPPY              SEQ ID NO:1294
EGPFVVIDLDTPTDPPPPYS             SEQ ID NO:1295
NEGPFVVIDLDTPTDPPPPY             SEQ ID NO:1296

[0118]

TABLE 9
PPPY Motif Containing Peptides from Human
Herpesvirus 7 Major Capsid Scaffold Protein
(GenBank Accession No. AAC40768)
PPPY                  WYPS       SEQ ID NO:1297
PPPY                  WYPSM      SEQ ID NO:1298
PPPY                  WYPSMP     SEQ ID NO:1299
PPPY                  WYPSMPG    SEQ ID NO:1300
PPPY                  WYPSMPGF   SEQ ID NO:1301
PPPY                  WYPSMPGFN  SEQ ID NO:1302
PPPY                  WYPSMPGFNY SEQ ID NO:1303
PPPY                  WYPSMPGFNYK SEQ ID NO:1304
PPPY                  WYPSMPGFNYKS SEQ ID NO:1305
PPPY                  WYPSMPGFNYKSR SEQ ID NO:1306
PPPY                  WYPSMPGFNYKSRG SEQ ID NO:1307
PPPY                  WYPSMPGFNYKSRGS SEQ ID NO:1308
PPPY                  WYPSMPGFNYKSRGSQ SEQ ID NO:1309
IPPPYWYP                         SEQ ID NO:1310
IPPPYWYPS                        SEQ ID NO:1311
IPPPYWYPSM                       SEQ ID NO:1312
IPPPYWYPSMP                      SEQ ID NO:1313
IPPPYWYPSMPG                     SEQ ID NO:1314
IPPPYWYPSMPGF                    SEQ ID NO:1315
IPPPYWYPSMPGFN                   SEQ ID NO:1316
IPPPYWYPSMPGFNY                  SEQ ID NO:1317
IPPPYWYPSMPGFNYK                 SEQ ID NO:1318
IPPPYWYPSMPGFNYKS                SEQ ID NO:1319
IPPPYWYPSMPGFNYKSR               SEQ ID NO:1320
IPPPYWYPSMPGFNYKSRG              SEQ ID NO:1321
IPPPYWYPSMPGFNYKSRGS             SEQ ID NO:1322
HIPPPYWY                         SEQ ID NO:1323
HIPPPYWYP                        SEQ ID NO:1324
HIPPPYWYPS                       SEQ ID NO:1325
HIPPPYWYPSM                      SEQ ID NO:1326
HIPPPYWYPSMP                     SEQ ID NO:1327
HIPPPYWYPSMPG                    SEQ ID NO:1328
HIPPPYWYPSMPGF                   SEQ ID NO:1329
HIPPPYWYPSMPGFN                  SEQ ID NO:1330
HIPPPYWYPSMPGFNY                 SEQ ID NO:1331
HIPPPYWYPSMPGFNYK                SEQ ID NO:1332
HIPPPYWYPSMPGFNYKS               SEQ ID NO:1333
HIPPPYWYPSMPGFNYKSR              SEQ ID NO:1334
HIPPPYWYPSMPGFNYKSRG             SEQ ID NO:1335
YHIPPPYW                         SEQ ID NO:1336
YHIPPPYWY                        SEQ ID NO:1337
YHIPPPYWYP                       SEQ ID NO:1338
YHIPPPYWYPS                      SEQ ID NO:1339
YHIPPPYWYPSM                     SEQ ID NO:1340
YHIPPPYWYPSMP                    SEQ ID NO:1341
YHIPPPYWYPSMPG                   SEQ ID NO:1342
YHIPPPYWYPSMPGF                  SEQ ID NO:1343
YHIPPPYWYPSMPGFN                 SEQ ID NO:1344
YHIPPPYWYPSMPGFNY                SEQ ID NO:1345
YHIPPPYWYPSMPGFNYK               SEQ ID NO:1346
YHIPPPYWYPSMPGFNYKS              SEQ ID NO:1347
YHIPPPYWYPSMPGFNYKSR             SEQ ID NO:1348
NYHIPPPY                         SEQ ID NO:1349
NYHIPPPYW                        SEQ ID NO:1350
NYHIPPPYWY                       SEQ ID NO:1351
NYHIPPPYWYP                      SEQ ID NO:1352
NYHIPPPYWYPS                     SEQ ID NO:1353
NYHIPPPYWYPSM                    SEQ ID NO:1354
NYHIPPPYWYPSMP                   SEQ ID NO:1355
NYHIPPPYWYPSMPG                  SEQ ID NO:1356
NYHIPPPYWYPSMPGF                 SEQ ID NO:1357
NYHIPPPYWYPSMPGFN                SEQ ID NO:1358
NYHIPPPYWYPSMPGFNY               SEQ ID NO:1359
NYHIPPPYWYPSMPGFNYK              SEQ ID NO:1360
NYHIPPPYWYPSMPGFNYKS             SEQ ID NO:1361
MNYHIPPPY                        SEQ ID NO:1362
MNYHIPPPYW                       SEQ ID NO:1363
MNYHIPPPYWY                      SEQ ID NO:1364
MNYHIPPPYWYP                     SEQ ID NO:1365
MNYHIPPPYWYPS                    SEQ ID NO:1366
MNYHIPPPYWYPSM                   SEQ ID NO:1367
MNYHIPPPYWYPSMP                  SEQ ID NO:1368
MNYHIPPPYWYPSMPG                 SEQ ID NO:1369
MNYHIPPPYWYPSMPGF                SEQ ID NO:1370
MNYHIPPPYWYPSMPGFN               SEQ ID NO:1371
MNYHIPPPYWYPSMPGFNY              SEQ ID NO:1372
MNYHIPPPYWYPSMPGFNYK             SEQ ID NO:1373
RMNYHIPPPY                       SEQ ID NO:1374
RMNYHIPPPYW                      SEQ ID NO:1375
RMNYHIPPPYWY                     SEQ ID NO:1376
RMNYHIPPPYWYP                    SEQ ID NO:1377
RMNYHIPPPYWYPS                   SEQ ID NO:1378
RMNYHIPPPYWYPSM                  SEQ ID NO:1379
RMNYHIPPPYWYPSMP                 SEQ ID NO:1380
RMNYHIPPPYWYPSMPG                SEQ ID NO:1381
RMNYHIPPPYWYPSMPGF               SEQ ID NO:1382
RMNYHIPPPYWYPSMPGFN              SEQ ID NO:1383
RMNYHIPPPYWYPSMPGFNY             SEQ ID NO:1384
NRMNYHIPPPY                      SEQ ID NO:1385
NRMNYHIPPPYW                     SEQ ID NO:1386
NRMNYHIPPPYWY                    SEQ ID NO:1387
NRMNYHIPPPYWYP                   SEQ ID NO:1388
NRMNYHIPPPYWYPS                  SEQ ID NO:1389
NRMNYHIPPPYWYPSM                 SEQ ID NO:1390
NRMNYHIPPPYWYPSMP                SEQ ID NO:1391
NRMNYHIPPPYWYPSMPG               SEQ ID NO:1392
NRMNYHIPPPYWYPSMPGF              SEQ ID NO:1393
NRMNYHIPPPYWYPSMPGFN             SEQ ID NO:1394
GNRMNYHIPPPY                     SEQ ID NO:1395
GNRMNYHIPPPYW                    SEQ ID NO:1396
GNRMNYHIPPPYWY                   SEQ ID NO:1397
GNRMNYHIPPPYWYP                  SEQ ID NO:1398
GNRMNYHIPPPYWYPS                 SEQ ID NO:1399
GNRMNYHIPPPYWYPSM                SEQ ID NO:1400
GNRMNYHIPPPYWYPSMP               SEQ ID NO:1401
GNRMNYHIPPPYWYPSMPG              SEQ ID NO:1402
GNRMNYHIPPPYWYPSMLPGF            SEQ ID NO:1403
YGNRMNYHIPPPY                    SEQ ID NO:1404
YGNRMNYHIPPPYW                   SEQ ID NO:1405
YGNRMNYHIPPPYWY                  SEQ ID NO:1406
YGNRMNYHIPPPYWYP                 SEQ ID NO:1407
YGNRMNYHIPPPYWYPS                SEQ ID NO:1408
YGNRMNYHIPPPYWYPSM               SEQ ID NO:1409
YGNRMNYHIPPPYWYPSMP              SEQ ID NO:1410
YGNRMNYHIPPPYWYPSMPG             SEQ ID NO:1411
DYGNRMNYHIPPPY                   SEQ ID NO:1412
DYGNRMNYHIPPPYW                  SEQ ID NO:1413
DYGNRMNYHIPPPYWY                 SEQ ID NO:1414
DYGNRMNYHIPPPYWYP                SEQ ID NO:1415
DYGNRMNYHIPPPYWYPS               SEQ ID NO:1416
DYGNRMNYHIPPPYWYPSM              SEQ ID NO:1417
DYGNRMNYHIPPPYWYPSMP             SEQ ID NO:1418
MDYGNRMNYHIPPPY                  SEQ ID NO:1419
MDYGNRMNYHIPPPYW                 SEQ ID NO:1420
MDYGNRMNYHIPPPYWY                SEQ ID NO:1421
MDYGNRMNYHIPPPYWYP               SEQ ID NO:1422
MDYGNRMNYHIPPPYWYPS              SEQ ID NO:1423
MDYGNRMNYHIPPPYWYPSM             SEQ ID NO:1424
RMDYGNRMNYHIPPPY                 SEQ ID NO:1425
RMDYGNRMNYHIPPPYW                SEQ ID NO:1426
RMDYGNRMNYHIPPPYWY               SEQ ID NO:1427
RMDYGNRMNYHIPPPYWYP              SEQ ID NO:1428
RMDYGNRMNYHIPPPYWYPS             SEQ ID NO:1429
LRMDYGNRMNYHIPPPY                SEQ ID NO:1430
LRMDYGNRMNYHIPPPYW               SEQ ID NO:1431
LRMDYGNRMNYHIPPPYWY              SEQ ID NO:1432
LRMDYGNRMNYHIPPPYWYP             SEQ ID NO:1433
SLRMDYGNRMNYHIPPPY               SEQ ID NO:1434
SLRMDYGNRMNYHIPPPYW              SEQ ID NO:1435
SLRMDYGNRMNYHIPPPYWY             SEQ ID NO:1436
ESLRMDYGNRMNYHIPPPY              SEQ ID NO:1437
ESLRMDYGNRMNYHIPPPYW             SEQ ID NO:1438
PESLRMDYGNRMNYHIPPPY             SEQ ID NO:1439

[0119]

TABLE 10
PPXY Motif Containing Peptides from Infectious
Pancreatic Necrosis Virus Structural Protein VP2
(GenBank Accession No. AAK18736)
EVELPPPY             SEQ ID NO:1440
EEVELPPPY            SEQ ID NO:1441
YEEVELPPPY           SEQ ID NO:1442
NYEEVELPPPY          SEQ ID NO:1443
ANYEEVELPPPY         SEQ ID NO:1444
SANYEEVELPPPY        SEQ ID NO:1445
ESANYEEVELPPPY       SEQ ID NO:1446
LESANYEEVELPPPY      SEQ ID NO:1447
RLESANYEEVELPPPY     SEQ ID NO:1448
NRLESANYEEVELPPPY    SEQ ID NO:1449
KNRLESANYEEVELPPPY   SEQ ID NO:1450
LKNRLESANYEEVELPPPY  SEQ ID NO:1451
ALKNRLESANYEEVELPPPY SEQ ID NO:1452

[0120]

TABLE 11
PPXY Motif Containing Peptides from Lassa Virus
Z Protein
(GenBank Accession No. AAC05816)
IRPPPYSP             SEQ ID NO:1453
SIRPPPYS             SEQ ID NO:1454
SIRPPPYSP            SEQ ID NO:1455
DSIRPPPY             SEQ ID NO:1456
DSIRPPPYS            SEQ ID NO:1457
DSIRPPPYSP           SEQ ID NO:1458
ADSIRPPPY            SEQ ID NO:1459
ADSIRPPPYS           SEQ ID NO:1460
ADSIRPPPYSP          SEQ ID NO:1461
AADSIRPPPY           SEQ ID NO:1462
AADSIRPPPYS          SEQ ID NO:1463
AADSIRPPPYSP         SEQ ID NO:1464
GAADSIRPPPY          SEQ ID NO:1465
GAADSIRPPPYS         SEQ ID NO:1466
GAADSIRPPPYSP        SEQ ID NO:1467
TGAADSIRPPPY         SEQ ID NO:1468
TGAADSIRPPPYS        SEQ ID NO:1469
TGAADSIRPPPYSP       SEQ ID NO:1470
PTGAADSIRPPPY        SEQ ID NO:1471
PTGAADSIRPPPYS       SEQ ID NO:1472
PTGAADSIRPPPYSP      SEQ ID NO:1473
PPTGAADSIRPPPY       SEQ ID NO:1474
PPTGAADSIRPPPYS      SEQ ID NO:1475
PPTGAADSIRPPPYSP     SEQ ID NO:1476
APPTGAADSIRPPPY      SEQ ID NO:1477
APPTGAADSIRPPPYS     SEQ ID NO:1478
APPTGAADSIRPPPYSP    SEQ ID NO:1479
TAPPTGAADSIRPPPY     SEQ ID NO:1480
TAPPTGAADSIRPPPYS    SEQ ID NO:1481
TAPPTGAADSIRPPPYSP   SEQ ID NO:1482
PTAPPTGAADSIRPPPY    SEQ ID NO:1483
PTAPPTGAADSIRPPPYS   SEQ ID NO:1484
PTAPPTGAADSIRPPPYSP  SEQ ID NO:1485
APTAPPTGAADSIRPPPY   SEQ ID NO:1486
APTAPPTGAADSIRPPPYS  SEQ ID NO:1487
APTAPPTGAADSIRPPPYSP SEQ ID NO:1488
AAPTAPPTGAADSIRPPPY  SEQ ID NO:1489
AAPTAPPTGAADSIRPPPYS SEQ ID NO:1490
SAAPTAPPTGAADSIRPPPY SEQ ID NO:1491

[0121]

TABLE 12
PPPY Motif Containing Peptides from Lymphocytic
Choriomeningitis Virus Ring Finger Protein
(GenBank Accession No. CAA10342)
SPPPPYEE             SEQ ID NO:1492
PSPPPPYE             SEQ ID NO:1493
PSPPPPYEE            SEQ ID NO:1494
APSPPPPY             SEQ ID NO:1495
APSPPPPYE            SEQ ID NO:1496
APSPPPPYEE           SEQ ID NO:1497
TAPSPPPPY            SEQ ID NO:1498
TAPSPPPPYE           SEQ ID NO:1499
TAPSPPPPYEE          SEQ ID NO:1500
STAPSPPPPY           SEQ ID NO:1501
STAPSPPPPYE          SEQ ID NO:1502
STAPSPPPPYEE         SEQ ID NO:1503
ISTAPSPPPPY          SEQ ID NO:1504
ISTAPSPPPPYE         SEQ ID NO:1505
ISTAPSPPPPYEE        SEQ ID NO:1506
KISTAPSPPPPY         SEQ ID NO:1507
KISTAPSPPPPYE        SEQ ID NO:1508
KISTAPSPPPPYEE       SEQ ID NO:1509
LKISTAPSPPPPY        SEQ ID NO:1510
LKISTAPSPPPPYE       SEQ ID NO:1511
LKISTAPSPPPPYEE      SEQ ID NO:1512
KLKISTAPSPPPPY       SEQ ID NO:1513
KLKISTAPSPPPPYE      SEQ ID NO:1514
KLKISTAPSPPPPYEE     SEQ ID NO:1515
TKLKISTAPSPPPPY      SEQ ID NO:1516
TKLKISTAPSPPPPYE     SEQ ID NO:1517
TKLKISTAPSPPPPYEE    SEQ ID NO:1518
PTKLKISTAPSPPPPY     SEQ ID NO:1519
PTKLKISTAPSPPPPYE    SEQ ID NO:1520
PTKLKISTAPSPPPPYEE   SEQ ID NO:1521
LPTKLKISTAPSPPPPY    SEQ ID NO:1522
LPTKLKISTAPSPPPPYE   SEQ ID NO:1523
LPTKLKISTAPSPPPPYEE  SEQ ID NO:1524
PLPTKLKISTAPSPPPPY   SEQ ID NO:1525
PLPTKLKISTAPSPPPPYE  SEQ ID NO:1526
PLPTKLKISTAPSPPPPYEE SEQ ID NO:1527
CPLPTKLKISTAPSPPPPY  SEQ ID NO:1528
CPLPTKLKISTAPSPPPPYE SEQ ID NO:1529
KCPLPTKLKISTAPSPPPPY SEQ ID NO:1530

[0122]

TABLE 13
PPXY Motif Containing Peptides from TT Virus ORF2
(GenBank Accession No. BAB19319)
PPPY                  RSEP       SEQ ID NO:1531
PPPY                  RSEPH      SEQ ID NO:1532
PPPY                  RSEPHT     SEQ ID NO:1533
PPPY                  RSEPHTE    SEQ ID NO:1534
PPPY                  RSEPHTEH   SEQ ID NO:1535
PPPY                  RSEPHTEHS  SEQ ID NO:1536
PPPY                  RSEPHTEHSR SEQ ID NO:1537
PPPY                  RSEPHTEHSRP SEQ ID NO:1538
PPPY                  RSEPHTEHSRPP SEQ ID NO:1539
PPPY                  RSEPHTEHSRPPP SEQ ID NO:1540
PPPY                  RSEPHTEHSRPPPP SEQ ID NO:1541
PPPY                  RSEPHTEHSRPPPPK SEQ ID NO:1542
PPPY                  RSEPHTEHSRPPPPKK SEQ ID NO:1543
GPPPYRSE                         SEQ ID NO:1544
GPPPYRSEP                        SEQ ID NO:1545
GPPPYRSEPH                       SEQ ID NO:1546
GPPPYRSEPHT                      SEQ ID NO:1547
GPPPYRSEPHTE                     SEQ ID NO:1548
GPPPYRSEPHTEH                    SEQ ID NO:1549
GPPPYRSEPHTEHS                   SEQ ID NO:1550
GPPPYRSEPHTEHSR                  SEQ ID NO:1551
GPPPYRSEPHTEHSRP                 SEQ ID NO:1552
GPPPYRSEPHTEHSRPP                SEQ ID NO:1553
GPPPYRSEPHTEHSRPPP               SEQ ID NO:1554
GPPPYRSEPHTEHSRPPPP              SEQ ID NO:1555
GPPPYRSEPHTEHSRPPPPK             SEQ ID NO:1556
QGPPPYRS                         SEQ ID NO:1557
QGPPPYRSE                        SEQ ID NO:1558
QGPPPYRSEP                       SEQ ID NO:1559
QGPPPYRSEPH                      SEQ ID NO:1560
QGPPPYRSEPHT                     SEQ ID NO:1561
QGPPPYRSEPHTE                    SEQ ID NO:1562
QGPPPYRSEPHTEH                   SEQ ID NO:1563
QGPPPYRSEPHTEHS                  SEQ ID NO:1564
QGPPPYRSEPHTEHSR                 SEQ ID NO:1565
QGPPPYRSEPHTEHSRP                SEQ ID NO:1566
QGPPPYRSEPHTEHSRPP               SEQ ID NO:1567
QGPPPYRSEPHTEHSRPPP              SEQ ID NO:1568
QGPPPYRSEPHTEHSRPPPP             SEQ ID NO:1569
PQGPPPYR                         SEQ ID NO:1570
PQGPPPYRS                        SEQ ID NO:1571
PQGPPPYRSE                       SEQ ID NO:1572
PQGPPPYRSEP                      SEQ ID NO:1573
PQGPPPYRSEPH                     SEQ ID NO:1574
PQGPPPYRSEPHT                    SEQ ID NO:1575
PQGPPPYRSEPHTE                   SEQ ID NO:1576
PQGPPPYRSEPHTEH                  SEQ ID NO:1577
PQGPPPYRSEPHTEHS                 SEQ ID NO:1578
PQGPPPYRSEPHTEHSR                SEQ ID NO:1579
PQGPPPYRSEPHTEHSRP               SEQ ID NO:1580
PQGPPPYRSEPHTEHSRPP              SEQ ID NO:1581
PQGPPPYRSEPHTEHSRPPP             SEQ ID NO:1582
WPQGPPPY                         SEQ ID NO:1583
WPQGPPPYR                        SEQ ID NO:1584
WPQGPPPYRS                       SEQ ID NO:1585
WPQGPPPYRSE                      SEQ ID NO:1586
WPQGPPPYRSEP                     SEQ ID NO:1587
WPQGPPPYRSEPH                    SEQ ID NO:1588
WPQGPPPYRSEPHT                   SEQ ID NO:1589
WPQGPPPYRSEPHTE                  SEQ ID NO:1590
WPQGPPPYRSEPHTEH                 SEQ ID NO:1591
WPQGPPPYRSEPHTEHS                SEQ ID NO:1592
WPQGPPPYRSEPHTEHSR               SEQ ID NO:1593
WPQGPPPYRSEPHTEHSRP              SEQ ID NO:1594
WPQGPPPYRSEPHTEHSRPP             SEQ ID NO:1595
YWPQGPPPY                        SEQ ID NO:1596
YWPQGPPPYR                       SEQ ID NO:1597
YWPQGPPPYRS                      SEQ ID NO:1598
YWPQGPPPYRSE                     SEQ ID NO:1599
YWPQGPPPYRSEP                    SEQ ID NO:1600
YWPQGPPPYRSEPH                   SEQ ID NO:1601
YWPQGPPPYRSEPHT                  SEQ ID NO:1602
YWPQGPPPYRSEPHTE                 SEQ ID NO:1603
YWPQGPPPYRSEPHTEH                SEQ ID NO:1604
YWPQGPPPYRSEPHTEHS               SEQ ID NO:1605
YWPQGPPPYRSEPHTEHSR              SEQ ID NO:1606
YWPQGPPPYRSEPHTEHSRP             SEQ ID NO:1607
GYWPQGPPPY                       SEQ ID NO:1608
GYWPQGPPPYR                      SEQ ID NO:1609
GYWPQGPPPYRS                     SEQ ID NO:1610
GYWPQGPPPYRSE                    SEQ ID NO:1611
GYWPQGPPPYRSEP                   SEQ ID NO:1612
GYWPQGPPPYRSEPH                  SEQ ID NO:1613
GYWPQGPPPYRSEPHT                 SEQ ID NO:1614
GYWPQGPPPYRSEPHTE                SEQ ID NO:1615
GYWPQGPPPYRSEPHTEH               SEQ ID NO:1616
GYWPQGPPPYRSEPHTEHS              SEQ ID NO:1617
GYWPQGPPPYRSEPHTEHSR             SEQ ID NO:1618
RGYWPQGPPPY                      SEQ ID NO:1619
RGYWPQGPPPYR                     SEQ ID NO:1620
RGYWPQGPPPYRS                    SEQ ID NO:1621
RGYWPQGPPPYRSE                   SEQ ID NO:1622
RGYWPQGPPPYRSEP                  SEQ ID NO:1623
RGYWPQGPPPYRSEPH                 SEQ ID NO:1624
RGYWPQGPPPYRSEPHT                SEQ ID NO:1625
RGYWPQGPPPYRSEPHTE               SEQ ID NO:1626
RGYWPQGPPPYRSEPHTEH              SEQ ID NO:1627
RGYWPQGPPPYRSEPHTEHS             SEQ ID NO:1628
TRGYWPQGPPPY                     SEQ ID NO:1629
TRGYWPQGPPPYR                    SEQ ID NO:1630
TRGYWPQGPPPYRS                   SEQ ID NO:1631
TRGYWPQGPPPYRSE                  SEQ ID NO:1632
TRGYWPQGPPPYRSEP                 SEQ ID NO:1633
TRGYWPQGPPPYRSEPH                SEQ ID NO:1634
TRGYWPQGPPPYRSEPHT               SEQ ID NO:1635
TRGYWPQGPPPYRSEPHTE              SEQ ID NO:1636
TRGYWPQGPPPYRSEPHTEH             SEQ ID NO:1637
QTRGYWPQGPPPY                    SEQ ID NO:1638
QTROYWPQGPPPYR                   SEQ ID NO:1639
QTRGYWPQGPPPYRS                  SEQ ID NO:1640
QTRGYWPQGPPPYRSE                 SEQ ID NO:1641
QTRGYWPQGPPPYRSEP                SEQ ID NO:1642
QTRGYWPQGPPPYRSEPH               SEQ ID NO:1643
QTRGYWPQGPPPYRSEPHT              SEQ ID NO:1644
QTRGYWPQGPPPYRSEPHTE             SEQ ID NO:1645
LQTRGYWPQGPPPY                   SEQ ID NO:1646
LQTRGYWPQGPPPYR                  SEQ ID NO:1647
LQTRGYWPQGPPPYRS                 SEQ ID NO:1648
LQTRGYWPQGPPPYRSE                SEQ ID NO:1649
LQTRGYWPQGPPPYRSEP               SEQ ID NO:1650
LQTRGYWPQGPPPYRSEPH              SEQ ID NO:1651
LQTRGYWPQGPPPYRSEPHT             SEQ ID NO:1652
ILQTRGYWPQGPPPY                  SEQ ID NO:1653
ILQTRGYWPQGPPPYR                 SEQ ID NO:1654
ILQTRGYWPQGPPPYRS                SEQ ID NO:1655
ILQTRGYWPQGPPPYRSE               SEQ ID NO:1656
ILQTRGYWPQGPPPYRSEP              SEQ ID NO:1657
ILQTRGYWPQGPPPYRSEPH             SEQ ID NO:1658
NILQTRGYWPQGPPPY                 SEQ ID NO:1659
NILQTRGYWPQGPPPYR                SEQ ID NO:1660
NILQTRGYWPQGPPPYRS               SEQ ID NO:1661
NILQTRGYWPQGPPPYRSE              SEQ ID NO:1662
NILQTRGYWPQGPPPYRSEP             SEQ ID NO:1663
RNILQTRGYWPQGPPPY                SEQ ID NO:1664
RNILQTRGYWPQGPPPYR               SEQ ID NO:1665
RNILQTRGYWPQGPPPYRS              SEQ ID NO:1666
RNILQTRGYWPQGPPPYRSE             SEQ ID NO:1667
LRNILQTRGYWPQGPPPY               SEQ ID NO:1668
LRNILQTRGYWPQGPPPYR              SEQ ID NO:1669
LRNILQTRGYWPQGPPPYRS             SEQ ID NO:1670
HLRNILQTRGYWPQGPPPY              SEQ ID NO:1671
HLRNILQTRGYWPQGPPPYR             SEQ ID NO:1672
DHLRNILQTRGYWPQGPPPY             SEQ ID NO:1673

Claims

1. A composition comprising a peptide associated with a transporter that is capable of increasing the uptake of said peptide by a mammalian cell, wherein said peptide includes an amino acid sequence motif PPXY and is capable of binding a type I WW-domain of the Nedd4 protein, wherein X is an amino acid.

2. The composition according to claim 1, wherein X is selected from the group consisting of proline (P), alanine (A), glutamic acid (E), asparagine (N), and arginine (R).

3. The composition of claim 1, wherein said transporter is capable of increasing the uptake of said peptide by a mammalian cell by at least 100%.

4. The composition of claim 1, wherein said transporter is capable of increasing the uptake of said peptide by a mammalian cell by at least 300%.

5. The composition of claim 1, wherein said peptide is covalently linked to said transporter.

6. The composition of claim 5, wherein said transporter is selected from the group consisting of penetratins, l-Tat49-57, d-Tat49-57, retro-inverso isomers of l- or d-Tat49-57, L-arginine oligomers, D-arginine oligomers, L-lysine oligomers, D-lysine oligomers, L-histidine oligomers, D-histidine oligomers, L-ornithine oligomers, D-ornithine oligomers, and HSV-1 structural protein VP22 and fragments thereof, and peptides having at least six contiguous amino acid residues that are L-arginine, D-arginine, L-lysine, D-lysine, L-histidine, D-histidine, L-ornithine, D-ornithine, or a combination thereof; and peptoid analogs thereof.

7. The composition according to claim 1, wherein said transporter is selected from the group consisting of liposomes, dendrimers, and siderophores.

8. The composition according to claim 1, wherein said peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of matrix proteins of rhabdoviruses, matrix proteins of filoviruses, Rous Sarcoma virus GAG protein, hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, TT virus ORF2 protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

9. The composition according to claim 1, wherein said peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of Ebola virus Matrix (EbVp40) protein, Rous Sarcoma virus GAG protein, Marburg virus matrix protein, VSV matrix protein, and Mason-Pfizer Monkey virus GAG protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

10. A composition comprising a hybrid polypeptide, said hybrid polypeptide consists of a peptide covalently linked to a peptidic transporter that is capable of increasing the uptake of said peptide by a mammalian cell by at least 100%, wherein said hybrid polypeptide consists of from about 8 to about 100 amino acid residues, and wherein said peptide comprises an amino acid sequence motif PPXY and is capable of binding a type I WW-domain of the Nedd4 protein, wherein X is an amino acid.

11. The composition according to claim 10, wherein said hybrid polypeptide consists of from about 9 to about 50 amino acid residues.

12. The composition according to claim 10, wherein said hybrid polypeptide consists of from about 12 to about 30 amino acid residues.

13. The composition according to claim 10, wherein X is selected from the group consisting of proline (P), alanine (A), glutamic acid (E), asparagine (N), and arginine (R).

14. The composition according to claim 10, wherein said peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of matrix proteins of rhabdoviruses, matrix proteins of filoviruses, Rous Sarcoma virus GAG protein, hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, TT virus ORF2 protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

15. The composition according to claim 10, wherein said peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of Ebola virus Matrix (EbVp40) protein, Rous Sarcoma virus GAG protein, Marburg virus matrix protein, VSV matrix protein, and Mason-Pfizer Monkey virus GAG protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

16. The composition according to claim 10, wherein said peptide does not include a contiguous amino acid sequence of Ebola virus Matrix (EbVp40) protein that is sufficient to impart an ability to bind the UEV domain of the human Tsg101 protein.

17. The composition according to claim 10, wherein said transporter that is capable of increasing the uptake of said peptide by a mammalian cell by at least 300%.

18. The composition according to claim 10, wherein said transporter is selected from the group consisting of penetratins, l-Tat49-57, retro-inverso isomers of l-Tat49-57, L-arginine oligomers, L-lysine oligomers, HSV-1 structural protein VP22 and fragments thereof, and peptides consisting of at least six contiguous amino acid residues that are a combination of two or more of L-arginine, L-lysine and L-histidine.

19. The composition according to claim 11, wherein said peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:24-36, SEQ ID NOs:154-295, SEQ ID NOs:296-438, SEQ ID NOs:439-581, SEQ ID NOs:582-724, SEQ ID NOs:725-1010, SEQ ID NOs:1011-1296, SEQ ID NOs:1297-1439, SEQ ID NOs:1440-1452, SEQ ID NOs:1453-1491, SEQ ID NOs:1492-1530, and SEQ ID NOs:1531-1673.

20. The composition according to claim 10, wherein said hybrid polypeptide does not contain a terminal L-histidine oligomer.

21. A composition comprising a hybrid polypeptide, said hybrid polypeptide consists of a peptide covalently linked to a peptidic transporter that is capable of increasing the uptake of said peptide by a mammalian cell by at least 200%, wherein said hybrid polypeptide consists of from about 10 to about 30 amino acid residues, and wherein said peptide comprises an amino acid sequence motif PPXY and is capable of binding a type I WW-domain of the Nedd4 protein, wherein X is an amino acid.

22. The composition of claim 21, wherein said hybrid polypeptide does not contain a terminal L-histidine oligomer of at least 6 histidine residues.

23. An isolated nucleic acid encoding the hybrid polypeptide according to claim 10.

24. An isolated nucleic acid encoding the hybrid polypeptide according to claim 11.

25. An isolated nucleic acid encoding the hybrid polypeptide according to claim 22.

26. A host cell comprising the isolated nucleic acid according to claim 23.

27. A host cell comprising the isolated nucleic acid according to claim 24.

28. A host cell comprising the isolated nucleic acid according to claim 25.

29. An isolated peptide consisting of a contiguous amino acid sequence of from 8 to about 30 amino acid residues of a viral protein selected from the group consisting of hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, and TT virus ORF2 protein, wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein, and wherein said peptide is capable of binding a type I WW-domain of the Nedd4 protein.

30. The isolated peptide according to claim 29, wherein said isolated peptide consists of from 9 to about 20 amino acid residues.

31. The isolated peptide of claim 29, wherein said peptide comprises of an amino acid sequence selected from the group consisting of SEQ ID NOs:24-36, SEQ ID NOs:154-295, SEQ ID NOs:296-438, SEQ ID NOs:439-581, SEQ ID NOs:582-724, SEQ ID NOs:725-1010, SEQ ID NOs:1011-1296, SEQ ID NOs:1297-1439, SEQ ID NOs:1440-1452, SEQ ID NOs:1453-1491, SEQ ID NOs:1492-1530, and SEQ ID NOs:1531-1673.

32. An isolated nucleic acid encoding the isolated peptide according to claim 29.

33. An isolated nucleic acid encoding the isolated peptide according to claim 30.

34. An isolated nucleic acid encoding the isolated peptide according to claim 31.

35. A method for treating an infection caused by a virus selected from the group consisting of hepatitis B virus and human herpesvirus 1, said method comprising: introducing into a patient in need of such treatment a peptide consisting of from 8 to about 30 amino acid residues and having an amino acid sequence motif PPXY, wherein X is an amino acid, and wherein said peptide is capable of binding a type I WW-domain of the Nedd4 protein.

36. The method of claim 35, wherein said introducing step comprises administering to the cells a nucleic acid encoding said peptide.

37. The method of claim 35, wherein X is selected from the group consisting of proline (P), alanine (A), glutamic acid (E), asparagine (N), and arginine (R).

38. The method of claim 35, wherein said peptide includes a contiguous amino acid sequence of at least 8 residues of a viral protein selected from the group consisting of matrix proteins of rhabdoviruses, matrix proteins of filoviruses, Rous Sarcoma virus GAG protein, Mason-Pfizer Monkey virus GAG protein, hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, TT virus ORF2 protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

39. A method for treating an infection caused by a virus selected from the group consisting of hepatitis B virus and human herpesvirus 1, said method comprising: administering to a patient in need of such treatment a composition comprising a peptide associated with a transporter that is capable of increasing the uptake of said peptide by a mammalian cell, wherein said peptide includes an amino acid sequence motif PPXY and is capable of binding a type I WW-domain of the Nedd4 protein, wherein X is an amino acid.

40. The method according to claim 39, wherein X is selected from the group consisting of proline (P), alanine (A), glutamic acid (E), asparagine (N), and arginine (R).

41. The method according to claim 39, wherein said transporter is capable of increasing the uptake of said peptide by a mammalian cell by at least 100%.

42. The method according to claim 39, wherein said transporter is capable of increasing the uptake of said peptide by a mammalian cell by at least 300%.

43. The method according to claim 39, wherein said peptide is covalently linked to said transporter.

44. The method according to claim 43, wherein said transporter is selected from the group consisting of penetrating, l-Tat49-57, d-Tat49-57, retro-inverso isomers of l- or d-Tat49-57, L-arginine oligomers, D-arginine oligomers, L-lysine oligomers, D-lysine oligomers, L-histidine oligomers, D-histidine oligomers, L-ornithine oligomers, D-ornithine oligomers, and HSV-1 structural protein VP22 and fragments thereof, and peptides having at least six contiguous amino acid residues that are L-arginine, D-arginine, L-lysine, D-lysine, L-histidine, D-histidine, L-ornithine, D-ornithine, or a combination thereof; and peptoid analogs thereof.

45. The method according to claim 39, wherein said transporter is selected from the group consisting of liposomes, dendrimers, and siderophores.

46. The method according to claim 39, wherein said peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of matrix proteins of rhabdoviruses, matrix proteins of filoviruses, Rous Sarcoma virus GAG protein, Mason-Pfizer Monkey virus GAG protein, hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, TT virus ORF2 protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

47. The method according to claim 39, wherein said peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of Ebola virus Matrix (EbVp40) protein, Rous Sarcoma virus GAG protein, Marburg virus matrix protein, VSV matrix protein, and Mason-Pfizer Monkey virus GAG protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

48. A method for treating an infection caused by a virus selected from the group consisting of hepatitis B virus and human herpesvirus 1, said method comprising: administering to a patient in need of such treatment a hybrid polypeptide, said hybrid polypeptide consists of a peptide covalently linked to a peptidic transporter that is capable of increasing the uptake of said peptide by a mammalian cell by at least 100%, wherein said hybrid polypeptide consists of from about 8 to about 100 amino acid residues, and wherein said peptide comprises an amino acid sequence motif PPXY and is capable of binding a type I WW-domain of the Nedd4 protein, wherein X is an amino acid.

49. The method according to claim 48, wherein said hybrid polypeptide consists of from about 9 to about 50 amino acid residues.

50. The method according to claim 48, wherein said hybrid polypeptide consists of from about 12 to about 30 amino acid residues.

51. The method according to claim 48, wherein X is selected from the group consisting of proline (P), alanine (A), glutamic acid (E), asparagine (N), and arginine (R).

52. The method according to claim 48, wherein said peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of matrix proteins of rhabdoviruses, matrix proteins of filoviruses, Rous Sarcoma virus GAG protein, Mason-Pfizer Monkey virus GAG protein, hepatitis B virus core antigen, human herpesvirus 4 latent membrane protein 2A, human herpesvirus 1 UL56 protein, human herpesvirus 7 major capsid scaffold protein, infectious pancreatic necrosis virus VP2 protein, Lassa virus Z protein, lymphocytic choriomeningitis virus ringer finger protein, TT virus ORF2 protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

53. The method according to claim 48, wherein said peptide includes a contiguous amino acid sequence of at least 6 amino acid residues of a viral protein selected from the group consisting of Ebola virus Matrix (EbVp40) protein, Rous Sarcoma virus GAG protein, Marburg virus matrix protein, VSV matrix protein, and Mason-Pfizer Monkey virus GAG protein, and wherein said contiguous amino acid sequence encompasses the PPXY motif of said viral protein.

54. The method according to claim 48, wherein said peptide does not include a contiguous amino acid sequence of Ebola virus Matrix (EbVp40) protein that is sufficient to impart an ability to bind the UEV domain of the human Tsg101 protein.

55. The method according to claim 48, wherein said transporter is capable of increasing the uptake of said peptide by a mammalian cell by at least 300%.

56. The method according to claim 48, wherein said transporter is selected from the group consisting of penetratins, l-Tat49-57, retro-inverso isomers of l-Tat49-57, L-arginine oligomers, L-lysine oligomers, HSV-1 structural protein VP22 and fragments thereof, and peptides consisting of at least six contiguous amino acid residues that include two or more of the group consisting of L-arginine, L-lysine and L-histidine.

57. The method according to claim 48, wherein said peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:24-36, SEQ ID NOs:154-295, SEQ ID NOs:296-438, SEQ ID NOs:439-581, SEQ ID NOs:582-724, SEQ ID NOs:725-1010, SEQ ID NOs:1011-1296, SEQ ID NOs:1297-1439, SEQ ID NOs:1440-1452, SEQ ID NOs:1453-1491, SEQ ID NOs:1492-1530, and SEQ ID NOs:1531-1673.

58. The method according to claim 48, wherein said hybrid polypeptide does not contain a terminal L-histidine oligomer.

59. A method for treating an infection caused by a virus selected from the group consisting of hepatitis B virus and human herpesvirus 1, said method comprising: administering to a patient in need of such treatment a composition comprising a hybrid polypeptide, said hybrid polypeptide consists of a peptide covalently linked to a peptidic transporter that is capable of increasing the uptake of said peptide by a mammalian cell by at least 200%, wherein said hybrid polypeptide consists of from about 10 to about 30 amino acid residues, and wherein said peptide comprises an amino acid sequence motif PPXY and is capable of binding a type I WW-domain of the Nedd4 protein, wherein X is an amino acid.