Methods for the inhibition of respiratory syncytial virus transmission

1. INTRODUCTION

The present invention relates to DP-178 (SEQ ID:1), a peptide corresponding to amino acids 638 to 673 of the HIV-1

LAI

transmembrane protein (TM) gp41, and portions, analogs, and homologs of DP-178 (SEQ ID:1), all of which exhibit anti-viral activity. Such anti-viral activity includes, but is not limited to, the inhibition of HIV transmission to uninfected CD-4

+

cells. Further, the invention relates to the use of DP-178 (SEQ ID:1) and DP-178 fragments and/or analogs or homologs as inhibitors of human and non-human retroviral, especially HIV, transmission to uninfected cells. Still further, the invention relates to the use of DP-178 as a HIV subtype-specific diagnostic. The present invention also relates to antiviral peptides analogous to DP-107, a peptide corresponding to amino acids 558 to 595 of the HIV-1

LAI

transmembrane protein (TM) gp41, that are present in other enveloped viruses. The present invention further relates to methods for identifying antiviral compounds that disrupt the interaction between DP-178 and DP-107, and/or between DP-107-like and DP-178-like peptides. The invention is demonstrated by way of a working example wherein DP-178 (SEQ ID:1), and a peptide whose sequence is homologous to DP-178 are each shown to be potent, non-cytotoxic inhibitors of HIV-1 transfer to uninfected CD-4

+

cells. The invention is further demonstrated by working examples wherein peptides having antiviral and/or structural similarity to DP-107 and DP-178 are identified.

2. BACKGROUND OF THE INVENTION

2.1. The Human Immenodeficiency Virus

The human immunodeficiency virus (HIV) has been implicated as the primary cause of the slowly degenerative immune system disease termed acquired immune deficiency syndrome (AIDS) (Barre-Sinoussi, F. et al., 1983, Science 220:868-870; Gallo, R. et al., 1984, Science 224:500-503). there are at least two distinct types of HIV: HIV-1 (Barre-Sinoussi, F. et al., 1983, Science 220:868-870; Gallo R. et al., 1984, Science 224:500-503) and HIV-2 (Clavel, F. et al., 1986, Science 233:343-346; Guyader, M. et al., 1987, Nature 326:662-669). Further, a large amount of genetic heterogeneity exists within populations of each of these types. Infection of human CD-4

+

T-lymphocytes with an HIV virus leads to depletion of the cell type and eventually to opportunistic infections, neurological dysfunctions, neoplastic growth, and ultimately death.

HIV is a member of the lentivirus family of retroviruses (Teich, N. et al., 1984, RNA Tumor Viruses, Weiss, R. et al., eds., CSH-Press, pp. 949-956). Retroviruses are small enveloped viruses that contain a diploid, single-stranded RNA genome, and replicate via a DNA intermediate produced by a virally-encoded reverse transcriptase, an RNA-dependent DNA polymerase. (Varmus, H., 1988, Science 240:1427-1439). Other retroviruses include, for example, oncogenic viruses such as human T-cell leukemia viruses (HTLV-I,-II,-III), and feline leukemia virus.

The HIV viral particle consists of a viral core, composed of capsid proteins, that contains the viral RNA genome and those enzymes required for early replicative events. Myristylated Gag protein forms an outer viral shell around the viral core, which is, in turn, surrounded by a lipid membrane envelope derived from the infected cell membrane. The HIV envelope surface glycoproteins are synthesized as a single 160 Kd precursor protein which is cleaved by a cellular S protease during viral budding into two glycoproteins, gp41 and gp120. gp41 is a transmembrane protein and gp120 is an extracellular protein which remains non-covalently associated with gp41, possibly in a trimeric or multimeric form (Hammarskjold, M. and Rekosh, D., 1989, Biochem. Biophys. Acta 989:269-280).

HIV is targeted to CD-4

+

cells because the CD-4 cell surface protein acts as the cellular receptor for the HIV-1 virus (Dalgleish, A. et al., 1984, Nature 312:763-767; Klatzmann et al., 1984, Nature 312:767-768; Maddon et al., 1986, Cell 47:333-348). Viral entry into cells is dependent upon gp120 binding the cellular CD-4

+

receptor molecules (McDougal, J. S. et al., 1986, Science 231:382-385; Maddon, P. J. et al., 1986, Cell 47:333-348) and thus explains HIV's tropism for CD-4

+

cells, while gp41 anchors the envelope glycoprotein complex in the viral membrane.

2.2. HIV Treatment

HIV infection is pandemic and HIV associated diseases represent a major world health problem. Although considerable effort is being put into the successful design of effective therapeutics, currently no curative anti-retroviral drugs against AIDS exist. In attempts to develop such drugs, several stages of the HIV life cycle have been considered as targets for therapeutic intervention (Mitsuya, H. et al., 1991, FASEB J. 5:2369-2381). For example, virally encoded reverse transcriptase has been one focus of drug development. A number of reverse-transcriptase-targeted drugs, including 2′,3′-dideoxynucleoside analogs such as AZT, ddI, ddC, and d4T have been developed which have been shown to been active against HIV (Mitsuya, H. et al., 1991, Science 249:1533-1544). While beneficial, these nucleoside analogs are not curative, probably due to the rapid appearance of drug resistant HIV mutants (Lander, B. et al., 1989, Science 243:1731-1734). In addition, the drugs often exhibit toxic side effects such as bone marrow suppression, vomiting, and liver function abnormalities.

Attempts are also being made to develop drugs which can inhibit viral entry into the cell, the earliest stage of HIV infection. Here, the focus has thus far been on CD4, the cell surface receptor for HIV. Recombinant soluble CD4, for example, has been shown to inhibit infection of CD-4

+

T-cells by some HIV-1 strains (Smith, D. H. et al., 1987, Science 238:1704-1707). Certain primary HIV-1 isolates, however, are relatively less sensitive to inhibition by recombinant CD-4 (Daar, E. et al., 1990, Proc. Natl. Acad. Sci. USA 87:6574-6579). In addition, recombinant soluble CD-4 clinical trials have produced inconclusive results (Schooley, R. et al., 1990, Ann. Int. Med. 112:247-253; Kahn, J. O. et al., 1990, Ann. Int. Med. 112:254-261; Yarchoan, R. et al., 1989, Proc. Vth Int. Conf. on AIDS, p. 564, MCP 137).

The late stages of HIV replication, which involve crucial virus-specific secondary processing of certain viral proteins, have also been suggested as possible anti-HIV drug targets. Late stage processing is dependent on the activity of a viral protease, and drugs are being developed which inhibit this protease (Erickson, J., 1990, Science 249:527-533). The clinical outcome of these candidate drugs is still in question.

Attention is also being given to the development of vaccines for the treatment of HIV infection. The HIV-1 envelope proteins (gp160, gp120, gp41) have been shown to be the major antigens for anti-HIV antibodies present in AIDS patients (Barin, et al., 1985, Science 228:1094-1096). Thus far, therefore, these proteins seem to be the most promising candidates to act as antigens for anti-HIV vaccine development. To this end, several groups have begun to use various portions of gp160, gp120, and/or gp41 as immunogenic targets for the host immune system. See for example, Ivanoff, L. et al., U.S. Pat. No. 5,141,867; Saith, G. et al., WO 92/22,654; Shafferman, A., WO 91/09,872; Formoso, C. et al., WO 90/07,119. Clinical results concerning these candidate vaccines, however, still remain far in the future.

Thus, although a great deal of effort is being directed to the design and testing of anti-retroviral drugs, a truly effective, non-toxic treatment is still needed.

3. SUMMARY OF THE INVENTION

The present invention relates to DP-178 (SEQ ID:1), a 36-amino acid synthetic peptide corresponding to amino acids 638 to 673 of the transmembrane protein (TM) gp41 from the HIV-1 isolate LAI, which exhibits potent anti-HIV-1 activity. As evidenced by the example presented below, in Section 6, the DP-178 (SEQ ID:1) anti-viral activity is so high that, on a weight basis, no other known anti-HIV agent is effective at concentrations as low as those at which DP-178 (SEQ ID:1) exhibits its inhibitory effects. The invention further relates to those portions, analogs, and homologs of DP-178 which also show such antiviral activity. The antiviral activity of such DP-178 portions, analogs, and homologs, includes, but is not limited to the inhibition of HIV transmission to uninfected CD-4

+

cells. The invention relates to the use of DP-178 (SEQ ID:1) and DP-178 fragments and/or analogs or homologs. Such uses may include, but are not limited to, the use of the peptides as inhibitors of human and non-human retroviral, especially HIV, transmission to uninfected cells, and as type and/or subtype-specific diagnostic tools.

An embodiment of the invention is demonstrated below wherein an extremely low concentration of DP-178 (SEQ ID:1), and very low concentrations of a DP-178 homolog (SEQ ID:3) are shown to be potent inhibitors of HIV-1 mediated CD-4

+

cell-cell fusion (i.e., syncytial formation) and infection of CD-4

+

cells by cell-free virus. Further, it is shown that DP-178 (SEQ ID:1) is not toxic to cells, even at concentrations 3 logs higher than the inhibitory DP-178 (SEQ ID:1) concentration.

The invention also relates to analogous DP178 peptides in other enveloped viruses that demonstrate similar antiviral properties.

The invention further relates to peptides analogous to DP-107 (SEQ ID NO:25), a peptide corresponding to amino acids 558-595 of the HIV-1

LAI

transmembrane protein (TM) of gp41, that are present in other enveloped viruses, and demonstrate antiviral properties. The present invention is based, in part, on the surprising discovery that the DP-107 and DP-108 domains of the gp41 protein non-covalently complex with each other, and that their interaction is necessary for the normal activity of the virus. The invention, therefore, further relates to methods for identifying antiviral compounds that disrupt the interaction between DP-107 and DP-178, and/or between DP-107-like and DP-178-like peptides.

Embodiments of the invention are demonstrated, below, wherein peptides having structural and/or similarity to DP-107 and DP-178 are identified.

3.1. Definitions

Peptides are defined herein as organic compounds comprising two or more amino acids covalently joined by peptide bonds. Peptides may be referred to with respect to the number of constituent amino acids, i.e., a dipeptide contains two amino acid residues, a tripeptide contains three, etc. Peptides containing ten or fewer amino acids may be referred to as oligopeptides, while those with more than ten amino acid residues are polypeptides.

Peptide sequences defined herein are represented by one-letter symbols for amino acid residues as follows:

A (alanine)

R (arginine)

N (asparagine)

D (aspartic acid)

C (cysteine)

Q (glutamine)

E (glutamic acid)

G (glycine)

H (histidine)

I (isoleucine)

L (leucine)

K (lysine)

M (methionine)

F (phenylalanine)

P (proline)

S (serine)

T (threonine)

W (tryptophan)

Y (tyrosine)

V (valine)

4. BRIEF DESCRIPTION OF THE FIGURES

FIG.

1

. Amino acid sequence of DP-178 (SEQ ID:1) derived from HIV

LAI

; DP-178 homologs derived from HIV-1

SF2

(DP-185; SEQ ID:3), HIV-1

RF

(SEQ ID:4), and HIV-1

MN

(SEQ ID:5); DP-178 homologs derived from amino acid sequences of two prototypic HIV-2 isolates, namely, HIV-2

rod

(SEQ ID:6) and HIV-2

NIHZ

(SEQ ID:7); control peptides: DP-180 (SEQ ID:2), a peptide incorporating the amino acid residues of DP-178 in a scrambled sequence; DP-118 (SEQ ID:10) unrelated to DP-178, which inhibits HIV-1 cell free virus infection; DP-125 (SEQ ID:8), unrelated to DP-178, was also previously shown to-inhibit HIV-1 cell free virus infection (Wild et al., 1992, Proc. Natl. Acad. Sci USA 89:10,537-10,541); DP-116 (SEQ ID:9), unrelated to DP-178 had previously been shown to be negative for inhibition of HIV-1 infection using the cell-free virus infection assay (Wild, et al., 1992, Proc. Natl. Acad. Sci USA 89:10,537-10,541). Throughout the figures, the one letter amino acid code is used.

FIG.

2

. Inhibition of HIV-1 cell-free virus infection by synthetic peptides. IC50 refers to the concentration of peptide that inhibits RT production from infected cells by 50% compared to the untreated control. Control: the level of RT produced by untreated cell cultures infected with the same level of virus as treated cultures.

FIG.

3

. Inhibition of HIV-1 and HIV-2 cell-free virus infection by the synthetic peptide DP-178 (SEQ ID:1). IC50: concentration of peptide that inhibits RT production by 50% compared to the untreated control. Control: Level of RT produced by untreated cell cultures infected with the same level of virus as treated cultures.

FIG.

4

A. Fusion Inhibition Assay. DP-178 (SEQ ID:1) inhibition of HIV-1 prototypic isolate-mediated syncytia formation. Data represents the number of virus-induced syncytia per cell.

FIG.

4

B. Fusion Inhibition Assay. DP-180 (SEQ ID:2): scrambled control peptide. DP-185 (SEQ ID:3): DP-178 homolog derived from HIV-1

SF2

isolate. Control: number of syncytia produced in the absence of peptide.

FIG.

5

. Fusion inhibition assay: HIV-1 vs. HIV-2. Data represents the number of virus-induced syncytia per well. ND: not done.

FIG.

6

. Cytotoxicity study of DP-178 (SEQ ID:1) and DP-116 (SEQ ID:9) on CEM cells. Cell proliferation data is shown.

FIG.

7

. Schematic representation of HIV-gp41 and maltose binding protein (MBP)-gp41 fusion proteins. DP107 and DP178 are synthetic peptides based on the two putative helices of gp41. The letter P in the DP107 boxes denotes an Ile to Pro mutation at amino acid number 578. Amino acid residues are numbered according to Meyers et al., Human Retroviruses and AIDS, 1991, Theoret. Biol. and Biophys. Group, Los Alamos Natl. Lab., Los Alamos, N.Mex.

FIG. 8. A

point mutation alters the conformation and anti-HIV activity of M41.

FIG.

9

. Abrogation of DP178 anti-HIV activity. Cell fusion assays were carried out in the presence of 10 nM DP178 and various concentrations of M41Δ178 or M41PΔ178.

FIG.

10

. Binding of DP178 to leucine zipper of gp41 analyzed by ELISA.

FIGS. 11A-B

. Models for a structural transition in the HIV-1 TM protein. Two models are proposed which indicate a structural transition from a native oligomer to a fusogenic state following a trigger event (possibly gp120 binding to CD4). Common features of both models include (1) the native state is held together by noncovalent protein-protein interactions to form the heterodimer of gp120/41 and other interactions, principally though gp41 interactive sites, to form homo-oligomers on the virus surface of the gp120/41 complexes; (2) shielding of the hydrophobic fusogenic peptide at the N-terminus (F) in the native state; and (3) the leucine zipper domain (DP107) exists as a homo-oligomer coiled coil only in the fusogenic state. The major differences in the two models include the structural state (native or fusogenic) in which the DP107 and DP178 domains are complexed to each other. In the first model (A;

FIG. 11A

) this interaction occurs in the native state and in B during the fusogenic state. When triggered, the fusion complex in the model depicted in (A) is generated through formation of coiled-coil interactions in homologous DP107 domains resulting in an extended α-helix. This conformational change positions the fusion peptide for interaction with the cell membrane. In the second model (B; FIG.

11

B), the fusogenic complex is stabilized by the association of the DP178 domain with the DP107 coiled-coil.

FIG.

12

. Motif design using heptad repeat positioning of amino acids of known coiled-coils.

FIG.

13

. Motif design using proposed heptad repeat positioning of amino acids of DP-107 and DP-178.

FIG.

14

. Hybrid motif design crossing GCN4 and DP-107.

FIG.

15

. Hybrid motif design crossing GCN4 and DP-178.

FIG.

16

. Hybrid motif design 107×178×4, crossing DP-107 and DP-178. This motif was found to be the most consistent at identifying relevant DP-107-like and DP-178-like peptide regions.

FIG.

17

. Hybrid motif design ALLMOTI5, crossing GCN4, DP-107, and DP-178.

FIG.

18

. Hybrid motif design crossing GCN4, DP-107, DP-178, c-Fos c-Jun, c-Myc, and Flu Loop 36.

FIG.

19

. Motifs designed to identify N-terminal proline-leucine zipper motifs.

FIG.

20

. Search results (SEQ ID NO:26) for HIV-1 (BRU isolate) envelope protein gp41. Sequence search motif designations: Spades (): 107×178×4; Hearts (♥) ALLMOTI5; Clubs (): PLZIP; Diamonds (♦): transmembrane region (the putative transmembrane domains were identified using a PC/Gene program designed to search for such peptide regions). Asterisk (*): Lupas method. The amino acid sequences identified by each motif are bracketed by the respective characters. Representative sequences chosen based on all searches are underlined and in bold. DP-107 and DP-178 sequences are marked, and additionally double-underlined and italicized.

FIG.

21

. Search results (SEQ ID NO:27) for human respiratory syncytial virus (RSV) strain A2 fusion glycoprotein F1. Sequence search motif designations are as in FIG.

20

.

FIG.

22

. Search results (SEQ ID NO:28) for simian immunodeficiency virus (SIV) envelope protein gp41 (AGM3 isolate). Sequence search motif designations are as in FIG.

20

.

FIG.

23

. Search results (SEQ ID NO:29) for canine distemper virus (strain Onderstepoort) fusion glycoprotein 1. Sequence search motif designations are as in FIG.

20

.

FIG.

24

. Search results (SEQ ID NO:30) for newcastle disease virus (strain Australia-Victoria/32) fusion glycoprotein F1. Sequence search motif designations are as in FIG.

20

.

FIG.

25

. Search results (SEQ ID NO:31) for human parainfluenza 3 virus (strain NIH 47885) fusion glycoprotein F1. Sequence search motif designations are as in FIG.

20

.

FIG.

26

. Search results (SEQ ID NO:32) for influenza A virus (strain A/AICHI/2/68) hemagglutinin precursor HA2. Sequence search designations are as in FIG.

20

.

FIG.

27

. Coiled-coil structural similarity and anti-RSV antiviral activity of 35-mer peptides synthesized utilizing the sequence of a 48-amino acid RSV F2 peptide (SEQ ID NO:33) which spans sequences identified utilizing the computer-assisted searches described herein. For the exact location and motifs utilized, see FIG.

21

. “+” symbols are relative indicators of either structural similarity or antiviral activity, with a greater number of “+” symbols indicating a higher relative similarity or antiviral activity.

FIG.

28

. Coiled-coil structural similarity and anti-RSV antiviral activity of 35-mer peptides synthesized utilizing the sequence of a 53-amino acid RSV F1 peptide (SEQ ID NO:34) which spans sequences identified utilizing the computer-assisted searches described herein. See

FIG. 21

for the exact location and motifs used. “+” symbols are as described for FIG.

27

.

FIG.

29

. Coiled-coil structural similarity and anti-human parainfluenza 3 virus (HPF3) antiviral activity of 35-mer peptides synthesized utilizing the sequence of a 56-amino acid HPF3 peptide (SEQ ID NO:35) which spans sequences identified utilizing computer-assisted searches described herein. For the exact location and motifs utilized, see FIG.

25

. “+” symbols are as described in FIG.

27

.

FIG.

30

. Coiled-coil structural similarity and anti-HPF3 antiviral activity of 35-mer peptides synthesized utilizing the sequence of a 70-amino acid HPF3 peptide (SEQ ID NO:36) which spans sequences identified utilizing the computer-assisted searches described herein. For the exact location and motifs utilized, see FIG.

25

. “+” symbols are as described in FIG.

27

.

5. DETAILED DESCRIPTION OF THE INVENTION

Described herein are peptides that exhibit potent antiviral activity. These peptides include DP-178 (SEQ ID:1), a gp41-derived 36 amino acid peptide, fragments and/or analogs of DP-178, and peptides which are homologous to DP-178. In addition, these peptides may include peptides exhibiting anti-viral activity which are analogous to DP-107, a 38 amino acid peptide corresponding to residues 558 to 595 of the HIV-1

LAI

transmembrane (TM) gp41 protein, and which are present in other enveloped viral proteins. Also described here are assays for testing the antiviral activities of such peptides. The present invention is based, in part, of the surprising discovery that the DP-107 and DP-178 domains of the gp41 protein complex with each other via non-covalent protein-protein interactions which are necessary for normal activity of the virus. As such, methods are described for the identification of antiviral compounds that disrupt the interaction between DP-107 and DP-178 peptides, and between DP-107-like and DP-178-like peptides. Finally, the use of the peptides of the invention as inhibitors of non-human and human viral and retroviral, especially HIV, transmission are detailed, as is the use of the peptides as diagnostic indicators of the presence of specific, viruses, especially retroviruses.

While not limited to any theory of operation, the following model is proposed to explain the potent anti-HIV activity of DP178, based, in part, on the experiments described in the working examples, infra. In the viral protein, gp41, DP178 corresponds to a putative α-helix region located in the C-terminal end of the gp41 ectodomain, and appears to associate with a distal site on gp41 whose interactive structure is influenced by the leucine zipper motif, a coiled-coil structure, referred to as DP107. The association of these two domains may reflect a molecular linkage or “molecular clasp” intimately involved in the fusion process. It is of interest that mutations in the C-terminal α-helix motif of gp41 (i.e., the D178 domain) tend to enhance the fusion ability of gp41, whereas mutations in the leucine zipper region (i.e., the DP107 domain) decrease or abolish the fusion ability of the viral protein. It may be that the leucine zipper motif is involved in membrane fusion while the C-terminal α-helix motif serves as a molecular safety to regulate the availability of the leucine zipper during virus-induced membrane fusion.

On the basis of the foregoing, two models are proposed of gp41-mediated membrane fusion which are schematically shown in

FIG. 11A-B

. The reason for proposing two models is that the temporal nature of the interaction between the regions defined by DP 107 and DP178 cannot, as yet, be pinpointed. Each model envisions two conformations for gp41-one in a “native” state as it might be found on a resting virion. The other in a “fusogenic” state to reflect conformational changes triggered following binding of gp120 to CD4 and just prior to fusion with the target cell membrane. The strong binding affinity between gp120 and CD4 may actually represent the trigger for the fusion process obviating the need for a pH change such as occurs for viruses that fuse within intracellular vesicles. The two major features of both models are: (1) the leucine zipper sequences (DP107) in each chain of oligomeric envelope are held apart in the native state and are only allowed access to one another in the fusogenic state so as to form the extremely stable coiled-coils, and (2) association of the DP178 and DP107 sites as they exist in gp41 occur either in the native or fusogenic state.

FIG. 11A

depicts DP178/DP107 interaction in the native state as a molecular class. On the other hand, if one assumes that the most stable form of the envelope occurs in the fusogenic state, the model in

FIG. 11B

can be considered.

When synthesized as peptides, both DP107 and DP178 are potent inhibitors of HIV infection and fusion, probably by virtue of their ability to form complexes with viral gp41 and interfere with its fusogenic process; e.g., during the structural transition of the viral protein from the native structure to the fusogenic state, the DP178 and DP107 peptides may gain access to their respective binding sites on the viral gp41, and exert a disruptive influence. DP107 peptides which demonstrate anti-HIV activity are described in-Applicants' co-pending application Ser. No. 07/927,532, filed Aug. 7, 1992, which is incorporated by reference herein in its entirety.

As shown in the working examples, infra, a truncated recombinant gp41 protein corresponding the ectodomain of gp41 containing both DP107 and DP178 domains (excluding the fusion peptide, transmembrane region and cytoplasmic domain of gp41) did not inhibit HIV-1 induced fusion. However, when a single mutation was introduced to disrupt the coiled-coil structure of the DP107 domain—a mutation which results in a total loss of biological activity of DP107 peptides—the inactive recombinant protein was transformed to an active inhibitor of HIV-1 induced fusion. This transformation may result from liberation of the potent DP178 domain from a molecular clasp with the leucine zipper, DP107 domain.

For clarity of discussion, the invention will be described for DP178 peptide inhibitors of HIV. However, the principles may be analogously applied to other fusogenic enveloped viruses, including but not limited to those viruses containing the peptides listed in Tables V through X, below.

5.1. DP-178 and DP-178-like Peptides

The peptide DP-178 (SEQ ID:1) of the invention corresponds to amino acid residues 638 to 673 of the transmembrane protein gp41 from the HIV-1

LAI

isolate, and has the 36 amino acid sequence (reading from amino to carboxy terminus):

NH

2

-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-COOH (SEQ ID: 1)

In addition to the full-length DP-178 (SEQ ID:1) 36-mer, the peptides of the invention may include truncations of the DP-178 (SEQ ID:1) peptide which exhibit antiviral activity. Such truncated DP-178 (SEQ ID:1) peptides may comprise peptides of between 3 and 36 amino acid residues (i.e., peptides ranging in size from a tripeptide to a 36-mer polypeptide), and may include but are not limited to those listed in Tables I and II, below. Peptide sequences in these tables-are listed from amino (left) to carboxy (right) terminus. “X” may represent an amino group (—NH

2

) and “Z” may represent a carboxyl (—COOH) group. Alternatively, as described below, “X” and/or “Z” may represent a hydrophobic group, an acetyl group, a FMOC group, an amido group, or a covalently attached macromolecule.

TABLE I

DP-178 (SEQ ID:1) CARBOXY TRUNCATIONS

X-YTS-Z

X-YTSL-Z

X-YTSLI-Z

X-YTSLIH-Z

X-YTSLIHS-Z

X-YTSLIHSL-Z

X-YTSLIHSLI-Z

X-YTSLIHSLIE-Z

X-YTSLIHSLIEE-Z

X-YTSLIHSLIEES-Z

X-YTSLIHSLIEESQ-Z

X-YTSLIHSLIEESQN-Z

X-YTSLIHSLIEESQNQ-Z

X-YTSLIHSLIEESQNQQ-Z

X-YTSLIHSLIEESQNQQE-Z

X-YTSLIHSLIEESQNQQEK-Z

X-YTSLIHSLIEESQNQQEKN-Z

X-YTSLIHSLIEESQNQQEKNE-Z

X-YTSLIHSLIEESQNQQEKNEQ-Z

X-YTSLIHSLIEESQNQQEKNEQE-Z

X-YTSLIHSLIEESQNQQEKNEQEL-Z

X-YTSLIHSLIEESQNQQEKNEQELL-Z

X-YTSLIHSLIEESQNQQEKNEQELLE-Z

X-YTSLIHSLIEESQNQQEKNEQELLEL-Z

X-YTSLIHSLIEESQNQQEKNEQELLELD-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDK-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKW-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKWA-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKWAS-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKWASL-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKWASLW-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWN-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNW-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-Z

The one letter amino acid code is used.

Additionally,

“X” may represent an amino group, a hydrophobic group, including but not limited to carbobenzoxyl, dansyl, or T-butyloxycarbonyl; an acetyl group; a 9-fluorenylmethoxy-carbonyl (FMOC) group; a macromolecular carrier group including but not limited to lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates.

“Z” may represent a carboxyl group; an amido group; a T-butyloxycarbonyl group; a macromolecular carrier group including but not limited to lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates.

TABLE II

DP-178 (SEQ ID:1) AMINO TRUNCATIONS

X-NWF-Z

X-WNWF-Z

X-LWNWF-Z

X-SLWNWF-Z

X-ASLWNWF-Z

X-WASLWNWF-Z

X-KWASLWNWF-Z

X-DKWASLWNWF-Z

X-LDKWASLWNWF-Z

X-ELDKWASLWNWF-Z

X-LELDKWASLWNWF-Z

X-LLELDKWASLWNWF-Z

X-ELLELDKWASLWNWF-Z

X-QELLELDKWASLWNWF-Z

X-EQELLELDKWASLWNWF-Z

X-NEQELLELDKWASLWNWF-Z

X-KNEQELLELDKWASLWNWF-Z

X-EKNEQELLELDKWASLWNWF-Z

X-QEKNEQELLELDKWASLWNWF-Z

X-QQEKNEQELLELDKWASLWNWF-Z

X-NQQEKNEQELLELDKWASLWNWF-Z

X-QNQQEKNEQELLELDKWASLWNWF-Z

X-SQNQQEKNEQELLELDKWASLWNWF-Z

X-ESQNQQEKNEQELLELDKWASLWNWF-Z

X-EESQNQQEKNEQELLELDKWASLWNWF-Z

X-IEESQNQQEKNEQELLELDKWASLWNWF-Z

X-LIEESQNQQEKNEQELLELDKWASLWNWF-Z

X-SLIEESQNQQEKNEQELLELDKWASLWNWF-Z

X-HSLIEESQNQQEKNEQELLELDKWASLWNWF-Z

X-IHSLIEESQNQQEKNEQELLELDKWASLWNWF-Z

X-LIHSLIEESQNQQEKNEQELLELDKWASLWNWF-Z

X-SLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-Z

X-TSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-Z

X-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-Z

The one letter amino acid code is used.

Additionally,

“X” may represent an amino group, a hydrophobic group, including but not limited to carbobenzoxyl, dansyl, or T-butyloxycarbonyl; an acetyl group; a 9-fluorenylmethoxy-carbonyl group; a macromolecular carrier group including but not limited to lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates.

“Z” may represent a carboxyl group; an amido group; a T-butyloxycarbonyl group; a macromolecular carrier group including but not limited to lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates.

The antiviral peptides of the invention also include analogs of DP-178 and/or DP-178 truncations which may include, but are not limited to, peptides comprising the DP-178 (SEQ ID:1) sequence, or DP-178 truncated sequence, containing one or more amino acid substitutions, insertions and/or deletions. Analogs of DP-178 homologs, described below, are also within the scope of the invention. The DP-178 analogs of the invention exhibit antiviral activity, and may, further, possess additional advantageous features, such as, for example, increased bioavailability, and/or stability, or reduced host immune recognition.

HIV-1 and HIV-2 envelope proteins are structurally distinct, but there exists a striking amino acid conservation within the DP-178-corresponding regions of HIV-1 and HIV-2. The amino acid conservation is of a periodic nature, suggesting some conservation of structure and/or function. Therefore, one possible class of amino acid substitutions would include those amino acid changes which are predicted to stabilize the structure of the DP-178 peptides of the invention.

Amino acid substitutions may be of a conserved or non-conserved nature. Conserved amino acid substitutions consist of replacing one or more amino acids of the DP-178 (SEQ ID:1) peptide sequence with amino acids of similar charge, size, and/or hydrophobicity characteristics, such as, for example, a glutamic acid (E) to aspartic acid (D) amino acid substitution. When only conserved substitutions are made, the resulting peptide is functionally equivalent to DP-178 (SEQ ID:1) or the DP-178 peptide from which it is derived. Non-conserved substitutions consist of replacing one or more amino acids of the DP-178 (SEQ ID:1) peptide sequence with amino acids possessing dissimilar charge, size, and/or hydrophobicity characteristics, such as, for example, a glutamic acid (E) to valine (V) substitution.

Amino acid insertions may consist of single amino acid residues or stretches of residues ranging from 2 to 15 amino acids in length. One or more insertions may be introduced into DP-178 (SEQ ID:1), DP-178 fragments, analogs and/or DP-178 homologs (described below).

Deletions of DP-178 (SEQ ID:1), DP-178 fragments, analogs, and/or DP-178 homologs (described below) are also within the scope of the invention. Such deletions consist of the removal of one or more amino acids from the DP-178 or DP-178-like peptide sequence, with the lower limit length of the resulting peptide sequence being 4 to 6 amino acids. Such deletions may involve a single contiguous or greater than one discrete portion of the peptide sequences.

The peptides of the invention may further include homologs of DP-178 (SEQ ID:1) and/or DP-178 truncations which exhibit antiviral activity. Such DP-178 homologs are peptides whose amino acid sequences are comprised of the amino acid sequences of peptide regions of other (i.e., other than HIV-1

LAI

) viruses that correspond to the gp41 peptide region from which DP-178 (SEQ ID:1) was derived. Such viruses may include, but are not limited to, other HIV-1 isolates and HIV-2 isolates. DP-178 homologs derived from the corresponding gp41 peptide region of other (i.e., non HIV-1

LAI

) HIV-1 isolates may include, for example, peptide sequences as shown below.

NH

2

-YT

NT

I

YT

L

L

EESQNQQEKNEQELLELDKWASLWNWF-COOH (DP-185; SEQ ID:3);

NH

2

-YT

GI

I

YN

L

L

EESQNQQEKNEQELLELDKWA

N

LWNWF-COOH (SEQ ID:4);

NH

2

-YTSLI

Y

SL

L

E

K

SQIQQEKNEQELLELDKWASLWNWF-COOH (SEQ ID:5).

SEQ ID:3 (DP-185), SEQ ID:4, and SEQ ID:5 are derived from-HIV-1

SF2

, HIV-1

RF

, and HIV-1

MN

isolates, respectively. Underlined amino acid residues refer to those residues that differ from the corresponding position in the DP-178 (SEQ ID:1) peptide. One such DP-178 homolog, DP-185 (SEQ ID:3), is described in the Working Example presented in Section 6, below, where it is demonstrated that DP-185 (SEQ ID:3) exhibits antiviral activity. The DP-178 homologs of the invention may also include truncations, amino acid substitutions, insertions, and/or deletions, as described above.

In addition, striking similarities, as shown in

FIG. 1

, exist within the regions of HIV-1 and HIV-2 isolates which correspond to the DP-178 sequence. A DP-178 homolog derived from the HIV-2

NIHZ

. isolate has the 36 amino acid sequence (reading from amino to carboxy terminus):

NH

2

-LEANISQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-COOH (SEQ ID:7)

Table III and Table IV show some possible truncations of the HIV-2

NIHZ

DP-178 homolog, which may comprise peptides of between 3 and 36 amino acid residues (i.e., peptides ranging in size from a tripeptide to a 36-mer polypeptide). Peptide sequences in these tables are listed from amino (left) to carboxy (right) terminus. “X” may represent an amino group (—NH

2

) and “Z” may represent a carboxyl (—COOH) group. Alternatively, as described below, “X” and/or “Z” may represent a hydrophobic group, an acetyl group, a FMOC group, an amido group, or a covalently attached macromolecule, as described below.

TABLE III

HIV-2

NIHZ

DP-178 homolog carboxy truncations.

X-LEA-Z

X-LEAN-Z

X-LEANI-Z

X-LEANIS-Z

X-LEANISQ-Z

X-LEANISQS-Z

X-LEANISQSL-Z

X-LEANISQSLE-Z

X-LEANISQSLEQ-Z

X-LEANISQSLEQA-Z

X-LEANISQSLEQAQ-Z

X-LEANISQSLEQAQI-Z

X-LEANISQSLEQAQIQ-Z

X-LEANISQSLEQAQIQQ-Z

X-LEANISQSLEQAQIQQE-Z

X-LEANISQSLEQAQIQQEK-Z

X-LEANISQSLEQAQIQQEKN-Z

X-LEANISQSLEQAQIQQEKNM-Z

X-LEANISQSLEQAQIQQEKNMY-Z

X-LEANISQSLEQAQIQQEKNMYE-Z

X-LEANISQSLEQAQIQQEKNMYEL-Z

X-LEANISQSLEQAQIQQEKNMYELQ-Z

X-LEANISQSLEQAQIQQEKNMYELQK-Z

X-LEANISQSLEQAQIQQEKNMYELQKL-Z

X-LEANISQSLEQAQIQQEKNMYELQKLN-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNS-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSW-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSWD-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSWDV-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSWDVF-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSWDVFT-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSWDVFTN-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSWDVFTNW-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

The one letter amino acid code is used.

Additionally,

“X” may represent an amino group, a hydrophobic group, including but not limited to carbobenzoxyl, dansyl, or T-butyloxycarbonyl; an acetyl group; a 9-fluorenylmethoxy-carbonyl (FMOC) group; a macromolecular carrier group including but not limited to lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates.

“Z” may represent a carboxyl group; an amido group; a T-butyloxycarbonyl group; a macromolecular carrier group including but not limited to lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates.

TABLE IV

HIV-2

NIHZ

DP-178 homolog amino truncations.

X-NWL-Z

X-TNWL-Z

X-FTNWL-Z

X-VFTNWL-Z

X-DVFTNWL-Z

X-WDVFTNWL-Z

X-SWDVFTNWL-Z

X-NSWDVFTNWL-Z

X-LNSWDVFTNWL-Z

X-KLNSWDVFTNWL-Z

X-QKLNSWDVFTNWL-Z

X-LQKLNSWDVFTNWL-Z

X-ELQKLNSWDVFTNWL-Z

X-YELQKLNSWDVFTNWL-Z

X-MYELQKLNSWDVFTNWL-Z

X-NMYELQKLNSWDVFTNWL-Z

X-KNMYELQKLNSWDVFTNWL-Z

X-EKNMYELQKLNSWDVFTNWL-Z

X-QEKNMYELQKLNSWDVFTNWL-Z

X-QQEKNMYELQKLNSWDVFTNWL-Z

X-IQQEKNMYELQKLNSWDVFTNWL-Z

X-QIQQEKNMYELQKLNSWDVFTNWL-Z

X-AQIQQEKNMYELQKLNSWDVFTNWL-Z

X-QAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-EQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-LEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-SLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-QSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-SQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-ISQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-NISQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-ANISQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-EANISQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

X-LEANISQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z

The one letter amino acid code is used.

Additionally,

“X” may represent an amino group, a hydrophobic group, including but not limited to carbobenzoxyl, dansyl, or T-butyloxycarbonyl; an acetyl group; a 9-fluorenylmethoxy-carbonyl (FMOC) group; a macromolecular carrier group including but not limited to lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates.

“Z” may represent a carboxyl group; an amido group; a T-butyloxycarbonyl group; a macromolecular carrier group including but not limited to lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates.

5.2. DP-107 and DP-178 Analogous Antiviral Peptides

Peptide sequences functionally corresponding, and thus analogous to, the DP-178 sequences of the invention, described, above, in Section 5.1 may be found in other, non-HIV-1 envelope viruses. Further, peptide sequences functionally corresponding, and thus analogous to, DP-107, an HIV-1-derived antiviral peptide, may also be found in other, non-HIV-1 envelope viruses. DP-107 is a 38 amino acid peptide corresponding to residues 558 to 595 of HIV-1

LAI

transmembrane (TM) gp41 protein, which exhibits potent anti-viral activity. DP-107 is more fully described in Applicant's co-pending U.S. patent application Ser. No. 07/927,532. These DP-107-like and DP-178-like analogous peptides and present in TM proteins of envelope viruses and preferably exhibit antiviral activity, most preferably antiviral activity which is specific to the virus in which their native sequences are found.

DP-107-like and DP-178-like peptides may be identified, for example, by utilizing a computer-assisted search strategy such as that described and demonstrated, below, in the Examples presented in Sections 9 through 16. The search strategy identifies regions in other viruses that are similar in predicted secondary structure to DP-107 and DP-178.

This search strategy is described fully, below, in the Example presented in Section 9. While this search strategy is based, in part, on a primary amino acid motif deduced from DP-107 and DP-178, it is not based solely on searching for primary amino acid sequence homologies, as such protein sequence homologies exist within, but not between major groups of viruses. For example, primary amino acid sequence homology is high within the TM protein of different strains of HIV-1 or within the TM protein of different isolates of simian immunodeficiency virus (SIV). Primary amino acid sequence homology between HIV-1 and SIV, however, is low enough so as not to be useful. It is not possible, therefore, to find DP-107 or DP-178-like peptides within other viruses, whether structurally, or otherwise, based on primary sequence homology, alone.

Further, while it would be potentially useful to identify primary sequence arrangements of amino acids based on the physical chemical characteristics of different classes of amino acids rather than based on the specific amino acids themselves, for instance, a by concentrating on the coiled-coil nature of the peptide sequence, a computer algorithm designed by Lupas et al. to identify such coiled-coil propensities of regions within proteins (Lupas, A., et al., 1991 Science 252:1162-1164) is inadequate for identifying protein regions analogous to DP-107 or DP-178.

Specifically, analysis of HIV-1 gp160(containing both gp120 and gp41) using the Lupas algorithm does not identify the coiled-coil region within DP-107. It does, however, identify a region within DP-178 beginning eight amino acids N-terminal to the start of DP-178 and ending eight amino acids from the C-terminus. The DP-107 peptide has been shown experimentally to form a stable coiled coil. A search based on the Lupas search algorithm, therefore, would not have identified the DP-107 coiled-coil region. Conversely, the Lupas algorithm identified the DP-178 region as a potential coiled-coil motif. However, the peptide DP-178 derived from this region failed to form a coiled coil in solution. A possible explanation for the inability of the Lupas search algorithm to accurately identify coiled-coil sequences within the HIV-1 TM, is that the Lupas algorithm is based on the structure of coiled coils from proteins that are not structurally or functionally similar to the TM proteins of viruses, antiviral peptides (e.g. DP-107 and DP-178) of which are an object of this invention.

The computer search strategy of the invention, as demonstrated in the Examples presented below, in Sections 9 through 16, successfully identifies regions of viral TM proteins similar to DP-107 or DP-178. This search strategy was designed to be used with a commercially-available sequence database packages, preferably PC/Gene. A series of motifs were designed and engineered to range in stringency from very strict to very broad, as discussed in Section 9.

Among the protein sequence search motifs which may be utilized in such a computer-assisted DP-107-like and DP-178-like antiviral peptide search are the 107×178×4 motif, the ALLMOTI5 motif, and the PLZIP series of motifs, each of which is described in the Example presented in Section 9, below, with 107×178×4 being preferred.

Coiled-coiled sequences are thought to consist of heptad amino acid repeats. For ease of description, the amino acid positions within the heptad repeats are sometimes referred to as A through G, with the first position being A, the second B, etc. The motifs used to identify DP-107-like and DP-178-like sequences herein are designed to specifically search for and identify such heptad repeats. In the descriptions of each of the motifs described, below, amino acids enclosed by brackets, i.e., [ ], designate the only amino acid residues that are acceptable at the given position, while amino acids enclosed by braces, i.e., { }, designate the only amino acids which are unacceptable at the given heptad position. When a set of bracketed or braced amino acids is followed by a number in parentheses i.e., ( ), it refers to the number of subsequent amino acid positions for which the designated set of amino acids hold, e.g., a (2) means “for the next two heptad amino acid positions”.

The ALLMOTI5 is written as follows:

{CDGHP]-{CFP} (2)-{CDGHP}-{CFP} (3)-

{CDGHP]-{CFP} (2)-{CDGHP}-{CFP} (3)-

{CDGHP]-{CFP}(2)-{CDGHP} -{CFP}(3)-

{CDGHP]-{CFP} (2)-{CDGHP}-{CFP} (3)-

{CDGHP]-{CFP} (2)-{CDGHP}-{CFP} (3)-

Translating this motif, it would read: “at the first (A) position of the heptad, any amino acid residue except C, D, G, H, or P is acceptable, at the next two (B,C) amino acid positions, any amino acid residue except C, F, or P is acceptable, at the fourth heptad position (D), any amino acid residue except C, D, G, H, or P is acceptable, at the next three (E, F, G) amino acid positions, any amino acid residue except C, F, or P is acceptable”. This motif is designed to search for five consecutive heptad repeats (thus the repeat of the first line five times), meaning that it searches for 35-mer sized peptides. It may also be designed to search for 28-mers, by only repeating the initial motif four times. With respect to the ALLMOTI5 motif, a 35-mer search is preferred. Those viral sequences identified via such an ALLMOTI5 motif are listed in Table V, below, at the end of this Section. The viral sequences listed in Table V potentially exhibit antiviral activity, may be useful in the identification of antiviral compounds, and are intended to be within the scope of the invention.

The 107×178×4 motif is written as follows:

[EFIKLNQSTVWY]-{CFMP} (2)-[EFIKLNQSTVWY]-{CFMP} (3)-

[EFIKLNQSTVWY]-{CFMP} (2)-[EFIKLNQSTVWY]-{CFMP} (3)-

[EFIKLNQSTVWY]-{CFMP} (2)-[EFIKLNQSTVWY]-{CFMP} (3)-

[EFIKLNQSTVWY]-{CFMP} (2)-[EFIKLNQSTVWY]-{CFMP} (3)-

Translating this mofif, it would read: “at the first (A) position of the heptad, any amino acid residue except E, F, I, K, L, N, Q, S, T, V, W, or Y is acceptable, at the next two (B,C) amino acid positions, any amino acid residue except C, F, M or P is accepatble, at the fourth position (D), any amino acid residue except E, F, I, K, L, N, Q, S, T, V, W, or Y is acceptable, at the next three (E, F, G) amino acid positions, any amino acid residue except C, F, M or P is acceptable”. This motif is designed to search for four consecutive heptad repeats (thus the repeat of the first line four times), meaning that it searches for 28-mer sized peptides. It may also be designed to search for 35-mers, by repeating the initial motif five times. With respect to the 107×178×4 motif, a 28-mer search is preferred. Those viral sequences identified via such a 107×178×4 motif are listed in Table V, below, at the end of this is Section. The viral sequences listed in Table V potentially exhibit antiviral activity, may be useful in the the identification of antiviral compounds, and are intended to be within the scope of the invention.

The PLZIP series of motifs are as listed in FIG.

19

. These motifs are designed to identify leucine zipper coiled-coil like heptads wherein at least one proline residue is present at some predefined distance N-terminal to the repeat. These PLZIP motifs find regions of proteins with similarities to HIV-1 DP-178 generally located just N-terminal to the transmembrane anchor. These motifs may be translated according to the same convention described above. Each line depicted in

FIG. 19

represents a single, complete search motif. “X” in these motifs refers to any amino acid residue. In instances wherein a motif contains two numbers within parentheses, this refers to a variable number of amino acid residues. For example, X (1,12)is translated to “the next one to twelve amino acid residues, inclusive, may be any amino acid”.

Tables VI through X, below, at the end of this Section, list hits from such PLZIP motifs. The viral sequences listed in Table VI through X potentially exhibit antiviral activity, may be useful in the the identification of antiviral compounds, and are intended to be within the scope of the invention.

The Examples presented in Sections 17 and 18, below, demonstrate that respiratory syncytial virus and parainfluenza virus sequences identified via such a computer search exhibit antiviral and/or structural characteristics similar to those of DP-107 or DP-178.

The DP-107-like and DP-178-like analogous peptides may, further, contain any of the additional groups described for DP-178, above, in Section 5.1. For example, these peptides may include any of the additional amino-terminal groups which “X”of Tables I through IV may represent, and may also include any of the carboxy-terminal groups which “Z” of Tables I through IV may represent.

Additionally, such DP-107-like and DP-178-like peptides may further include DP-107-like or DP-178-like peptides, such as those listed in Tables V through X, above, containing one or more amino acid substitutions, insertions, and/or deletions. Also, analogs of such DP-107-like and DP-178-like peptides are intended to be within the scope of the invention. Such analogs of the invention may exhibit increased antiviral activity, and may, further, posses increased bioavailability, and/or stability, or reduced immune recognition.

The DP-107-like and DP-178-like amino acid substitutions, insertions and deletions, are as described for DP-178, above, in Section 5.1. Analog modifications are as described, below, in Section 5.3.

TABLE V

Search Results Summary for 107 × 178 × 4 and

ALLMOTI5 Motifs

107 × 178 × 4

ALLMOTI5

LIBRARY FILE

LIBRARY FILE

PENV_AVIRE

420-468

PENV1_FRSFV

341-375

PENV_AVISN

426-474

FENV2_FRSPV

341-378

PENV_BAEVM

395-452

PENV_AVIRE

420-472

PENV_BIV06

544-603

631-695

PENV_AVISN

426-478

PENV_BIV27

573-632

660-724

PENV_BAEVM

390-456

PENV_BLVAF

304-377

PENV_BIV06

530-610

635-695

PENV_BLVAU

304-377

PENV_BIV27

559-639

664-724

PENV_BLVAV

304-377

PENV_BLVAF

304-379

PENV_BLVB2

311-377

PENV_BLVAU

304-379

PENV_BLVB5

304-377

PENV_BLVAV

304-379

PENV_BLVJ

304-377

PENV_BLVB2

304-379

PENV_CAEVG

165-192

PENV_BLVB5

304-379

PENV_EIAV1

688-712

PENV_BLVJ

304-379

PENV_EIAV2

668-695

PENV_CAEVC

157-196

615-720

751-785

847-895

PENV_EIAV3

668-712

PENV_CAEVG

154-193

613-718

749-783

845-893

PENV_EIAV5

669-696

PENV_EIAV1

436-525

559-593

668-716

PENV_EIAV9

668-712

PENV_EIAV2

436-525

559-593

658-692

PENV_EIAVC

668-712

PENV_EIAV3

436-525

559-593

658-716

PENV_EIAVW

668-712

PENV_EIAV5

437-526

560-594

659-693

PENV_EIAVY

668-712

PENV_EIAV9

436-525

559-593

658-716

PENV_FENV1

517-544

PENV_EIAVC

436-525

559-593

658-716

PENV_FIVPE

650-680

722-749.

PENV_EIAVW

436-525

559-593

658-716

PENV_FIVSD

639-668

720-747

PENV_EIAVY

436-525

559-593

658-716

PENV_FIVT2

640-679

721-748

PENV_FENV1

503-555

567-604

PENV_FLVC6

509-538

PENV_FIVPE

610-690

715-756

PENV_FLVGL

490-519

PENV_FIV8D

601-688

713-754

PENV_FLVLB

510-539

PENV_FIVT2

609-689

714-755

PENV_FLVSA

487-516

PENV_FLVC6

497-549

661-595

PENV_FOAMV

318-355

866-893

PENV_FLVGL

478-530

542-576

PENV_FSVGA

510-539

PENV_FLVLB

498-550

562-598

PENV_FSVGB

490-519

PENV_FLVSA

475-527

539-573

PENV_FSVSM

493-522

PENV_FOAMV

321-355

563-693

866-903

PENV_GALV

523-564

PENV_FRSFB

318-354

PENV_HTL1A

342-376

PENV_FSVGA

498-550

562-596

PENV_HTL1C

342-376

PENV_FSVGB

476-530

542-576

PENV_HTL1M

342-376

PENV_FSVSM

481-524

545-579

PENV_HTLV2

336-370

PENV_FSVST

498-532

PENV_HV1A2

544-592

630-682

790-825

PENV_GALV

523-575

587-621

PENV_HV1B1

545-594

631-683

791-818

PENV_HTL1A

321-383

PENV_HV1B8

540-589

626-678

786-813

PENV_HTL1C

316-383

PENV_HV1BN

582-590

628-679

787-815

PENV_HTL1M

321-383

PENV_HV1BR

550-599

636-688

798-823

PENV_HTLV2

317-377

PENV_HV1C4

557-608

643-695

803-835

PENV_HV1A2

497-593

612-711

766-845

PENV_HV1EL

543-591

628-680

PENV_HV1B1

509-594

610-712

767-843

PENV_HV1H2

545-594

631-683

791-818

PENV_HV1B8

500-589

605-707

762-838

PENV_HV1H3

545-594

631-683

791-818

PENV_HV1BN

501-590

609-708

783-831

PENV_HV1J3

556-605

642-694

802-829

PENV_HV1BR

510-599

615-717

772-841

PENV_HV1JR

622-675

783-811

PENV_HV1C4

510-806

626-724

779-855

PENV_HV1KB

555-596

637-677

776-824

PENV_HV1EL

502-591

607-709

768-829

PENV_HV1MA

547-595

633-707

794-826

PENV_HV1H2

505-594

610-712

767-836

PENV_HV1MF

543-592

629-681

789-816

PENV_HV1H3

505-594

610-712

767-843

PENV_HV1MN

567-595

632-684

791-819

PENV_HV1J3

517-605

622-723

778-843

PENV_HV1ND

536-583

621-673

783-813

PENV_HV1JR

497-586

603-704

759-835

PENV_HV1OY

544-593

630-704

789-820

PENV_HV1KB

511-545

585-599

618-718

772-848

PENV_HV1PV

545-594

631-683

791-818

PENV_HVIMA

507-596

617-714

770-825

PENV_HV1RH

554-602

640-692

800-832

PENV_HV1MF

503-592

622-710

765-841

PENV_HV181

536-585

622-674

782-809

PENV_HV1MN

506-595

617-713

774-841

PENV_HV183

541-589

627-679

787-815

PENV_HV1ND

495-584

801-702

757-825

PENV_HV18C

545-593

631-683

PENV_HV1OY

497-593

610-711

766-842

PENV_HV1W1

545-593

631-683

791-818

PENV_HV1PV

605-594

610-712

767-843

PENV_HV1W2

538-584

622-674

782-809

PENV_HV1RH

507-603

619-721

776-852

PENV_HV1Z2

542-591

628-680

790-820

PENV_HV1S1

496-585

602-703

758-830

PENV_HV1Z6

545-593

630-682

792-622

PENV_HV1S3

494-590

607-708

763-837

PENV_HV1Z8

573-601

634-678

797-828

PENV_HV1SC

498-594

611-712

767-834

PENV_HV1ZH

545-594

627-666

791-823

PENV_HV1W1

498-594

611-712

767-836

PENV_HV2BE

532-591

621-648

653-697

PENV_HV1W2

489-584

602-703

758-827

PENV_HV2CA

534-593

623-650

655-699

PENV_HV1Z2

502-591

607-709

764-831

PENV_HV2D1

523-550

555-582

644-688

PENV_HV1Z6

504-593

609-711

766-840

PENV_HV2G1

524-551

555-583

613-640

645-693

PENV_HV1Z8

512-601

617-675

682-719

774-831

PENV_HV2NZ

524-551

556-583

613-640

662-889

PENV_HV1ZH

522-594

612-712

777-839

PENV_HV2RO

533-592

622-698

PENV_HV2BE

510-595

617-680

PENV_HV2S2

527-554

559-586

648-682

PENV_HV2CA

512-597

619-709

PENV_HV2SB

557-584

614-673

PENV_HV2D1

501-586

608-698

PENV_HV2ST

527-554

559-586

648-692

PENV_HV2G1

502-587

609-699

PENV_MCFF

473-612

PENV_HV2NZ

488-587

609-699

PENV_MCFF3

488-515

PENV

—

HV2RO

511-596

616-708

PENV_MLVAV

517-544

PENV_HV2S2

505-590

612-702

PENV_MLVCB

510-539

PENV_HV2SB

526-588

614-700

PENV_MLVF5

523-553

PENV_HV2ST

505-590

612-702

PENV_MLVFF

523-553

PENV_IPMAE

367-422

465-527

PENV_MLVFP

523-553

PENV_JSRV

403-455

571-605

PENV_MLVHO

510-540

PENV_MCFF

473-525

537-571

PENV_MLVKI

40-81

PENV_MCFF3

474-526

538-572

PENV_MLVMO

502-543

PENV_MLVAV

503-555

567-601

PENV_MLVRD

497-538

PENV_MLVCB

498-550

562-596

PENV_MLVRK

497-538

PENV_MLVF5

520-564

576-610

PENV_MMTVB

458-485

562-589

PENV_MLVFF

520-564

576-610

PENV_MMTVG

458-465

562-589

PENV_MLVFP

520-564

576-610

PENV_MPMV

422-470

PENV_MLVHO

504-551

563-597

PENV_MSVFB

57-84

PENV_MLVKI

40-92

104-138

PENV_OMVVS

42-69

196-223

780-807

PENV_MLVMO

502-554

566-600

PENV_RMCFV

487-517

PENV_MLVRD

497-549

551-595

PENV_SFV1

14-41

866-901

PENV_MLVRK

497-549

561-598

PENV_SFV3L

18-45

319-357

673-700

863-898

PENV_MMTVB

477-539

556-612

PENV_SIVA1

661-588

592-619

652-679

697-724

PENV_MMTVG

477-539

556-612

PENV_SIVAG

566-593

597-624

658-685

703-730

PENV_MPMV

408-474

PENV_SIVAI

548-603

634-708

PENV_MSVFB

43-95

107-141

PENV_SIVAT

590-617

651-678

PENV_OMVVS

22-64

185-223

664-746

780-816

PENV_SIVCZ

526-584

627-654

PENV_RMCFV

484-528

540-574

PENV_SIVGB

589-650

784-816

PENV_RSFFV

342-376

PENV_SIVM1

550-609

671-715

PENV_SFV1

1-41

101-140

154-205

321-355

563-651

658-693

866-904

PENV_SIVM2

156-215

277-289

PENV_SFV3L

5-46

158-209

319-357

560-706

863-901

PENV_SIVMK

553-608

PENV_SIVA1

269-310

551-823

643-693

PENV_SIVML

549-608

PENV_SIVAG

558-628

651-899

808-852

PENV_SIVS4

553-612

642-669

691-718

PENV_SIVAI

257-291

336-370

535-607

627-684

792-840

PENV_SIVSP

554-595

646-722

PENV_SIVAT

264-298

549-621

644-692

796-833

PENV_SMRVH

400-462

PENV_SIVCZ

283-291

330-365

512-584

669-703

803-837

PENV_SRV1

409-471

PENV_SIVGB

586-654

677-725

PENV_VILV

773-800

PENV_SIVM1

114-151

465-506

528-613

635-725

809-864

PENV_VILV1

780-807

PENV_SIVM2

71-116

134-219

245-331

PENV_VILV2

782-809

PENV_SIVMK

464-505

540-812

638-724

PHEMA_CVBLY

208-242

PENV_SIVML

464-505

540-612

638-724

PHEMA_CVBM

208-242

PENV_SIVS4

466-509

517-616

638-728

812-853

PHEMA_CVBQ

208-242

PENV_SIVSP

470-513

521-620

642-732

811-848

PHEMA_CVHOC

208-242

PENV_SMRVH

400-466

PHEMA_IAAIC

387-453

PENV_SRV1

409-475

PHEMA_IABAN

371-437

PENV_VILV

21-62

184-222

637-740

773-809

PHEMA_IABUD

381-451

PENV_VILV1

21-62

184-222

643-746

780-816

PHEMA_IACKA

381-451

PENV_VILV2

21-62

184-222

645-748

782-818

PHEMA_IACKG

382-441

494-528

PHEMA_CVBLY

208-242

PHEMA_IACKP

396-426

PHEMA_CVBM

208-242

PHEMA_IACKG

396-426

PHEMA_CVBQ

208-242

PHEMA_IACKV

384-443

PHEMA_CVHOC

208-242

PHEMA_IADA1

381-451

PHEMA_IAAIC

380-458

PHEMA_IADA2

423-453

499-543

PHEMA_IABAN

364-440

PHEMA_IADA3

387-453

PHEMA_IABUD

378-454

PHEMA_IADA4

418-478

PHEMA_IACKA

378-454

PHEMA_IADCZ

381-451

PHEMA_IACKG

108-142

375-475

494-528

PHEMA_IADE1

402-453

506-533

PHEMA_IACKP

360-452

487-532

PHEMA_IADH1

371-437

PHEMA_IACKQ

360-452

487-532

PHEMA_IADH2

371-437

PHEMA_IACKS

377-469

504-549

PHEMA_IADH3

371-437

PHEMA_IACKV

112-146

377-469

PHEMA_IADH4

371-437

PHEMA_IADA1

377-454

PHEMA_IADH5

371-437

PHEMA_IADA2

377-476

495-547

PHEMA_IADH6

371-437

PHEMA_IADA3

380-453

PHEMA_IADH7

371-437

PHEMA_IADA4

379-478

506-548

PHEMA_IADIR

415-446

PHEMA_IADCZ

378-454

PHEMA_IADM2

387-453

PHEMA_IADE1

21-55

377-472

PHEMA_IADNZ

381-451

PHEMA_IADH1

364-440

PHEMA_IADU3

387-453

PHEMA_IADH2

364-440

PHEMA_IAEN7

387-453

PHEMA_IADH3

364-440

PHEMA_IAFPR

384-442

PHEMA_IADH4

364-440

PHEMA_IAGRE

381-451

PHEMA_IADH5

364-440

PHEMA_IAGU2

505-532

PHEMA_IADH6

364-440

PHEMA_IAGUA

504-531

PHEMA_IADH7

364-440

PHEMA_IAHAL

386-452

PHEMA_IADIR

379-471

506-551

PHEMA_IAHC6

388-457

PHEMA_IADM1

21-55

PHEMA_IAHC7

388-457

PHEMA_IADM2

380-456

PHEMA_IAHCD

388-457

PHEMA_IADNY

21-55

PHEMA_IAHDE

388-457

PHEMA_IADNZ

378-454

PHEMA_IAHFO

386-452

PHEMA_IADU1

21-55

PHEMA_IAHK6

386-452

PHEMA_IADU3

380-456

PHEMA_IAHK7

386-452

PHEMA_IAEN7

380-456

PHEMA_IAHLE

388-457

PHEMA_IAFPR

377-477

PHEMA_IAHLO

388-457

PHEMA_IAGRE

378-454

PHEMA_IAHMI

386-452

PHEMA_IAGU2

378-473

PHEMA_IAHNM

386-452

PHEMA_IAGUA

377-476

PHEMA_IAHNN

388-457

PHEMA_IAHAL

379-455

PHEMA_IAHPR

388-457

PHEMA_IAHC6

112-146

360-484

503-537

PHEMA_IAHRO

386-452

PHEMA_IAHC7

112-146

360-484

503-537

PHEMA_IAHSA

386-452

PHEMA_IAHCD

360-484

503-537

PHEMA_IAHSP

388-457

PHEMA_IAHDE

360-484

503-537

PHEMA_IAHSW

388-457

PHEMA_IAHFO

379-455

PHEMA_IAHTE

386-452

PHEMA_IAHK6

379-455

PHEMA_IAHTO

386-455

PHEMA_IAHK7

379-455

PHEMA_IAHUR

386-452

PHEMA_IAHLE

112-146

360-484

503-537

PHEMA_IAKIE

425-478

PHEMA_IAHLO

112-146

360-484

503-537

PHEMA_IALEN

425-478

PHEMA_IAHMI

379-455

PHEMA_IAMAA

380-450

PHEMA_IAHNM

379-455

PHEMA_IAMAB

385-455

PHEMA_IAHNN

112-146

360-484

503-537

PHEMA_IAMAO

387-453

PHEMA_IAHPR

112-146

360-484

503-537

PHEMA_IAME1

387-453

PHEMA_IAHRO

379-455

PHEMA_IAME2

387-453

PHEMA_IAHSA

379-455

PHEMA_IAME6

371-437

PHEMA_IAHSP

112-146

360-484

503-537

PHEMA_IAMIN

382-441

PHEMA_IAHSW

112-146

360-484

503-537

PHEMA_IANT6

387-453

PHEMA_IAHTE

379-455

PHEMA_IAPIL

505-534

PHEMA_IAHTO

379-455

PHEMA_IAPUE

425-478

PHEMA_IAHUR

379-455

PHEMA_IARUD

351-451

PHEMA_IAJAP

375-467

502-547

PHEMA_IASE2

381-451

PHEMA_IAKIE

376-478

506-541

PHEMA_IASH2

506-547

PHEMA_IALEN

376-478

506-548

PHEMA_IASTA

384-443

PHEMA_IAMAA

377-453

PHEMA_IATKI

415-445

PHEMA_IAMAB

382-458

PHEMA_IATKM

381-451

PHEMA_IAMAO

380-456

PHEMA_IATKO

507-534

PHEMA_IAME1

380-456

PHEMA_IATKP

424-454

493-539

PHEMA_IAME2

380-456

PHEMA_IATKR

381-422

PHEMA_IAME6

384-440

PHEMA_IATKW

419-449

600-538

PHEMA_IAMIN

108-142

375-475

PHEMA_IAUDO

387-453

PHEMA_IANT6

380-456

PHEMA_IAUSS

425-478

PHEMA_IAPIL

378-477

496-534

PHEMA_IAVI7

388-454

PHEMA_IAPUE

376-478

506-548

PHEMA_IAWIL

424-477

PHEMA_IARUD

378-454

PHEMA_IAZCO

387-453

PHEMA_IASE2

378-454

PHEMA_IAZH2

371-437

PHEMA_IASH2

379-474

506-552

PHEMA_IAZH3

371-437

PHEMA_IASTA

112-148

377-469

PHEMA_IAZIN

418-478

506-547

PHEMA_IATKI

379-471

508-551

PHEMA_IAZNJ

418-478

506-547

PHEMA_IATKM

378-454

PHEMA_IAZUK

387-453

PHEMA_IATKO

392-470

504-548

PHEMA_INBBE

400-431

439-463

PHEMA_IATKP

378-454

493-540

PHEMA_INBBO

390-421

429-473

PHEMA_IATKR

30-84

374-474

PHEMA_INBEN

398-429

437-481

PHEMA_IATKW

373-472

487-539

PHEMA_INBHK

391-418

429-473

PHEMA_IATRA

21-55

PHEMA_INBLE

399-430

438-482

PHEMA_IAUDO

387-458

PHEMA_INBMD

389-420

428-472

PHEMA_IAUSS

376-478

608-548

PHEMA_INBME

393-424

432-476

PHEMA_IAVI7

381-457

PHEMA_INBOR

398-429

437-481

PHEMA_IAWIL

375-477

605-547

PHEMA_INBSI

399-429

437-481

PHEMA_IAZCO

380-456

PHEMA_INBUS

391-422

430-474

PHEMA_IAZH2

364-440

PHEMA_INBVI

393-424

432-476

PHEMA_IAZH3

364-440

PHEMA_INBVK

400-431

439-483

PHEMA_IAZIN

379-478

506-548

PHEMA_INCCA

495-571

PHEMA_IAZNJ

379-478

506-548

PHEMA_INCEN

483-559

PHEMA_IAZUK

380-456

PHEMA_INCGL

483-559

PHEMA_INBBE

388-473

PHEMA_INCHY

482-558

PHEMA_INBBO

378-463

PHEMA_INCJH

496-572

PHEMA_INBEN

386-471

PHEMA_INCKV

482-558

PHEMA_INBHK

381-463

PHEMA_INCMI

482-558

PHEMA_INBLE

387-472

PHEMA_INCNA

482-559

PHEMA_INBMD

377-462

PHEMA_INCP1

483-559

PHEMA_INBME

381-468

PHEMA_INCP2

483-559

PHEMA_INBOR

386-471

PHEMA_INCP3

483-559

PHEMA_INBSI

386-471

PHEMA_INCTA

483-559

PHEMA_INBUS

379-464

PHEMA_INCYA

483-559

PHEMA_INBVI

381-466

PHEMA_NDVA

64-91

PHEMA_INBVK

388-473

PHEMA_NDVB

64-91

PHEMA_INCCA

483-571

PHEMA_NDVD

64-91

PHEMA_INCEN

471-559

PHEMA_NDVH

64-91

PHEMA_INCGL

471-559

PHEMA_NDV1

64-91

PHEMA_INCHY

470-558

PHEMA_NDVM

64-91

PHEMA_INCJH

484-572

PHEMA_NDVQ

64-91

PHEMA_INCKY

470-558

PHEMA_NDVTG

64-91

PHEMA_INCMI

470-558

PHEMA_NDVU

64-91

PHEMA_INCNA

470-558

PHEMA_PHODV

39-66

46-73

PHEMA_INCP1

471-559

PHEMA_PI1HW

79-110

366-393

PHEMA_INCP2

471-559

PHEMA_PI3B

66-93

PHEMA_INCP3

471-559

PHEMA_PI3H4

27-61

PHEMA_INCTA

471-559

PHEMA_PI3HA

27-61

PHEMA_INCYA

471-559

PHEMA_PI3HT

27-76

PHEMA_MEASE

46-90

PHEMA_PI3HU

23-70

PHEMA_MEASH

46-90

PHEMA_PI3HV

27-61

PHEMA_MEASI

46-87

PHEMA_PI3HW

27-61

PHEMA_MEASY

46-87

PHEMA_PI3HX

27-61

PHEMA_MUMPM

34-99

PHEMA_RACVI

166-214

256-283

PHEMA_MUMPR

34-99

PHEMA_SEND5

79-106

PHEMA_MUMPS

34-99

PHEMA_SENDF

79-106

PHEMA_NDVA

8-52

477-529

PHEMA_SENDH

79-106

PHEMA_NDVB

1-49

PHEMA_SENDJ

79-106

PHEMA_NDVD

1-49

PHEMA_SENDZ

79-106

PHEMA_NDVM

1-49

PHEMA_SV41

22-52

394-421

PHEMA_NDVQ

1-49

PHEMA_VACCC

119-146

175-202

216-243

PHEMA_NDVTG

1-49

PHEMA_VACCI

109-146

175-202

216-243

PHEMA_NDVU

1-49

PHEMA_VACCT

119-146

175-202

216-243

PHEMA_PHODV

39-73

PHEMA_VACCV

109-146

175-202

215-242

PHEMA_PI1HW

66-110

PVENV_DHVI1

318-366

PHEMA_PI2H

247-281

PVENV_EAV

120-147

PHEMA_PI2HT

247-281

PVENV_THOGV

313-347

PHEMA_PI3B

38-93

PVF03_VACCC

71-110

185-212

PHEMA_PI3H4

13-110

394-428

PVF03_VACCV

71-110

185-212

PHEMA_PI3HA

20-110

394-428

PVF05_VACCP

33-60

PHEMA_PI3HT

13-110

394-428

PVF05_VACCV

33-60

PHEMA_PI3HU

13-110

394-428

PVF11_VACCC

274-321

PHEMA_PI3HV

13-110

394-428

PVF11_VACCP

270-317

PHEMA_PI3HW

13-110

394-428

PVF12_VACCC

10-37

113-140

554-581

PHEMA_PI3HX

13-110

394-428

PVF12_VACCP

10-37

113-140

554-481

PHEMA_PI4HA

54-88

PVF16_VACCC

35-62

152-179

PHEMA_RACVI

166-214

256-290

PVF16_VACCP

35-62

152-179

PHEMA_RINDK

46-87

PVFP4_FOWPV

146-173

PHEMA_RINDL

46-87

191-225

PVFU8_ORFNZ

59-86

PHEMA_SEND5

57-110

PVFU8_VACCC

37-64

PHEMA_SENDF

57-110

PVFU8_VACCV

37-64

PHEMA_SENDH

57-110

PVG01_VACCC

225-252

301-335

PHEMA_SENDJ

57-110

PVG01_VACCV

164-191

240-274

PHEMA_SENDZ

57-110

PVG01_VARV

225-252

301-335

PHEMA_SV41

18-52

387-421

PVG02_VACCV

96-123

PHEMA_SV5

27-82

PVG02_VARV

96-123

PHEMA_SV5LN

27-82

PVG03_HSVEB

146-176

PVENV_BEV

195-229

PVG03_HSVEK

146-176

PVENV_DHVI1

318-366

PVG05_VACCC

48-75

131-161

225-289

355-389

PVENV_MCV1

252-286

PVG05_VARV

48-75

124-161

255-289

355-389

PVENV_MCV2

252-286

PVG07_HSVI1

71-98

PVENV_THOGV

313-354

PVG09_VACCC

308-338

PVENV_VACCC

257-295

PVG09_VACCV

271-301

PVENV_VACCI

257-295

PVG09_VARV

308-338

PVENV_VACCP

257-295

PVG12_SFV1R

11-45

PVENV_VACCV

257-295

PVG17_HSVI1

177-204

PVF01_VACCC

46-80

124-158

PVG18_HSVI1

174-208

PVF01_VACCV

46-80

124-158

PVG1_SPV1R

260-287

PVF03_VACCC

71-110

PVG1_SPV4

287-314

383-410

PVF03_VACCV

71-110

PVG22_HSVI1

373-400

581-622

668-705

766-824

PVF05_VACCC

81-129

282-320

PVG24_HSVI1

31-58

PVF05_VACCP

81-129

282-320

PVG28_HSVI1

253-290

497-528

PVF05_VACCV

81-129

293-321

PVG2R_AMEPV

33-64

91-118

PVF11_VACCC

217-258

269-315

PVG2_SPV1R

285-326

PVF11_VACCP

213-254

265-311

PVG2_SPV4

146-173

175-205

262-310

PVF12_VACCC

1-67

102-143

199-236

350-388

544-581

PVG34_HSVI1

95-122

PVF12_VACCP

1-67

102-143

199-236

350-388

544-581

PVG37_HSVI1

442-469

PVF16_VACCC

155-194

PVG39_HSVI1

651-678

1088-1115

PVF16_VACCP

155-194

PVG3L_AMEPV

2-29

PVFP3_FOWPV

1-43

PVG3_SPV1R

15-49

PVFP4_FOWPV

139-173

239-273

PVG3_SPV4

18-52

87-148

PVFP7_FOWPV

23-57

PVG45_HSVSA

138-165

PVFPL_FOWP1

77-111

PVG46_HSVI1

142-169

346-373

897-924

973-1007

PVFUS_VACCC

30-64

PVG48_HSVSA

360-394

PVFUS_VACCV

30-64

PVG4R_AMEPV

4-31

PVG01_BPP22

94-135

400-468

475-513

608-659

PVG4_SPV1R

116-146

PVG01_HSVI1

271-306

512-563

591-647

730-764

PVG51_HSVI1

34-61

87-114

PVG01_VACCC

301-339

PVG52_HSVSA

47-74

PVG01_VACCV

240-276

PVG56_HSVI1

582-609

PVG01_VARV

301-339

PVG5_SPV1R

65-92

PVG03_HSVEB

143-177

PVG5_SPV4

56-83

PVG03_HSVEK

143-177

PVG63_HSVI1

550-584

PVG03_VARV

64-98

PVG64_HSVI1

477-504

PVG05_VACCC

117-168

255-289

355-389

PVG65_HSVI1

1213-1254

PVG05_VARV

117-158

255-289

355-389

PVG66_HSVI1

362-406

PVG06_HSVI1

61-109

PVG67_HSVI1

1342-1369

PVG07_HSVI1

69-103

PVG68_HSVI1

261-288

PVG07_VACCC

114-175

324-358

PVG72_HSVI1

447-481

PVG07_VARV

114-175

324-358

PVG75_HSVI1

388-422

PVG09_VACCC

304-338

PVG76_HSVI1

200-227

PVG09_VACCV

267-301

PVG7_SPV4

14-44

PVG09_VARV

304-338

PVGF1_IBVB

1230-1260

2408-2435

PVG10_HSVI1

63-97

PVGL2_CVBF

399-426

642-676

1022-1084

1278-1305

PVG12_SPV1R

11-45

PVGL2_CVBL9

399-426

1022-1084

1278-1305

PVG16_HSVSA

58-95

PVGL2_CVBLY

399-426

642-676

1022-1084

1278-1305

PVG17_HSVI1

92-129

177-211

PVGL2_CVBM

399-426

642-676

1022-1084

1278-1305

PVG18_HSVI1

174-208

215-256

PVGL2_CVBQ

399-426

642-676

1022-1084

1278-1305

PVG1L_AMEPV

407-441

PVGL2_CVBV

399-426

642-676

1022-1084

1278-1305

PVG1_SPV1R

136-170

256-297

320-357

PVGL2_CVH22

770-797

809-875

1056-1112

PVG1_SPV4

287-321

PVGL2_CVM4

643-684

1030-1092

PVG22_HSVI1

117-158

437-629

660-892

899-1056

PVGL2_CVMA6

36-63

591-632

978-1040

PVG24_HSVI1

7-72

74-108

PVGL2_CVMJH

502-543

889-951

PVG27_HSVI1

164-219

PVGL2_CVPFS

69-110

692-733

1072-1145

1353-1389

PVG28_HSVI1

253-290

PVGL2_CVPPU

69-107

690-731

1067-1143

1351-1387

PVG2R_AMEPV

29-63

184-218

PVGL2_CVPR8

468-509

845-921

1129-1165

PVG2_SPV1R

222-256

285-328

PVGL2_CVPRM

468-509

845-921

1129-1165

PVG2_SPV4

255-310

PVGL2_EBV

68-102

PVG33_HSVI1

149-183

PVGL2_FIPV

189-233

454-481

709-736

1072-1148

1356-1392

PVG34_HSVI1

345-379

PVGL2_IBV6

809-836

876-903

1057-1091

PVG35_HSVI1

17-90

PVGL2_IBVB

808-836

875-902

1056-1090

PVG37_HSVI1

435-472

PVGL2_IBVD2

809-836

876-903

1057-1091

PVG38_HSVI1

84-118

PVGL2_IBVK

808-836

875-902

1056-1090

PVG39_HSVI1

124-158

266-300

PVGL2_IBVM

808-835

875-902

1056-1090

PVG3_SPV1R

8-49

162-196

203-244

PVGLB_EBV

95-122

631-658

PVG3_SPV4

6-54

87-121

PVGLB_HCMVA

25-88

397-424

440-467

851-878

PVG43_HSVI1

116-150

282-296

394-361

643-677

PVGLB_HCMVT

50-88

397-424

435-462

852-879

PVG45_HSVSA

121-162

PVGLB_HSVB1

427-454

PVG46_HSVI1

45-88

939-1078

1251-1321

PVGLB_HSVB2

447-474

PVG48_HSVI1

169-207

PVGLB_HSVBC

426-453

PVG48_HSVSA

360-417

611-866

733-787

PVGLB_HSVE1

443-470

934-961

PVG49_HSVSA

68-102

PVGLB_HSVE4

486-513

616-643

PVG4R_AMEPV

4-38

PVGLB_HSVEA

443-470

934-961

PVG4_SPV4

89-130

PVGLB_HSVEB

443-470

934-961

PVG51_HSVI1

34-73

89-123

PVGLB_HSVEL

443-470

933-960

PVG51_HSVSA

29-70

123-157

162-196

PVGLB_HSVMD

93-120

352-379

PVG53_HSVI1

67-127

PVGLB_MCMVS

381-408

441-475

PVG54_HSVI1

355-396

PVGLC_HSV11

469-510

PVG55_HSVI1

101-135

PVGLC_HSV1K

469-510

PVG56_HSVSA

126-178

PVGLC_HSVEB

124-151

PVG58_HSVI1

151-192

578-612

644-678

750-784

846-880

1111-1145

PVGLC_HSVMB

63-97

PVG59_HSVI1

10-72

89-123

PVGLC_HSVMG

62-96

PVG59_HSVSA

169-209

PVGLC_HSVMM

63-97

PVG5_SPV1R

65-103

PVGLC_VZVD

295-322

PVG61_HSVI1

265-299

PVGLC_VZVS

295-322

PVG63_HSVI1

546-584

PVGLE_HSV2

111-148

PVG85_HSVI1

805-839

1213-1254

PVGLF_BRSVA

38-65

154-202

216-243

442-469

486-531

PVG66_HSVI1

154-188

328-410

PVGLF_BRSVC

38-65

154-202

216-243

444-471

488-533

PVG67_HSVI1

379-413

501-546

1321-1369

1476-1541

PVGLF_BRSVR

38-65

154-202

216-243

444-471

488-533

PVG68_HSVI1

245-288

PVGLF_CDVO

262-293

340-387

PVG72_HSVI1

447-484

723-767

912-949

PVGLF_HRSV1

38-65

154-203

442-471

488-515

PVG75_HSVI1

271-305

388-422

PVGLF_HRSVA

38-65

154-202

213-243

488-518

PVG8_SPV1R

5-51

PVGLF_HRSVL

38-65

154-202

216-243

444-471

488-515

PVGF1_IBVB

142-179

1233-1267

2119-2156

3388-3424

3475-3513

3517-3556

3761-3795

PVGLF_HRSVR

38-65

154-202

213-243

442-471

488-518

PVGH3_HCMVA

10-44

PVGLF_MEASE

228-262

PVGL2_CVBF

642-676

850-885

993-1088

1263-1305

PVGLF_MEASI

231-265

PVGL2_CVBL9

850-885

993-1109

1263-1305

PVGLF_MEASY

228-262

PVGL2_CVBLY

642-676

850-885

993-1109

1263-1305

PVGLF_MUMPM

20-54

447-488

PVGL2_CVBM

642-676

858-885

993-1109

1263-1305

PVGLF_MUMPR

20-54

447-488

PVGL2_CVBQ

642-676

850-885

993-1109

1263-1305

PVGLF_MUNP8

151-178

426-511

PVGL2_CVBV

642-676

850-885

993-1109

1263-1305

PVGLF_NDVA

151-178

426-512

PVGL2_CVH22

770-916

1055-1112

PVGLF_NDVB

151-178

426-512

PVGL2_CVM4

643-684

1001-1117

1270-1315

PVGLF_NDVI

151-178

426-512

PVGL2_CVMA5

591-632

949-1079

1217-1283

PVGLF_NDVM

151-178

426-512

PVGL2_CVMJH

502-543

860-976

1129-1174

PVGLF_NDVT

151-178

428-512

PVGL2_CVPFS

69-110

448-482

692-733

889-923

1040-1166

1352-1380

PVGLF_NDVTG

151-178

426-512

PVGL2_CVPPU

69-110

446-480

690-731

667-921

1038-1184

1351-1387

PVGLF_NDVU

151-178

428-512

PVGL2_CVPR8

224-258

468-509

665-899

816-892

1120-1185

PVGLF_PHODV

36-83

221-262

309-336

PVGL2_CVPRM

224-258

468-509

665-899

818-962

1128-1165

PVGLF_PI1HC

147-174

210-266

PVGL2_EBV

68-102

PVGLF_PI2H

90-117

141-175

238-266

463-528

PVGL2_FIPV

169-245

451-486

695-736

892-926

1043-1189

1355-1392

PVGLF_PI2HG

90-117

141-175

238-266

483-528

PVGL2_IBV6

791-905

1057-1091

PVGLF_PI2HT

90-117

141-176

238-266

483-528

PVGL2_IBVB

437-478

772-904

1056-1090

PVGLF_PI3B

115-182

207-241

459-497

PVGL2_IBVD2

773-905

1057-1091

PVGLF_PI3H4

115-182

207-241

457-497

PVGL2_IBVK

437-478

772-904

1056-1090

PVGLF_RINDK

224-265

458-485

PVGL2_IBVM

437-478

772-904

1056-1090

PVGLF_RINDL

224-265

458-506

PVGLB_HCMVA

43-88

128-162

436-484

844-878

PVGLF_SEND6

122-149

211-245

480-507

PVGLB_HCMVT

22-88

128-162

437-485

845-879

PVGLF_SENDF

122-149

211-245

480-507

PVGLB_HSVI1

828-890

PVGLF_SENDH

122-149

211-245

480-507

PVGLB_HSV1F

827-889

PVGLF_SENDJ

122-149

211-245

480-507

PVGLB_HSV1K

827-889

PVGLF_SENDZ

122-149

211-245

480-507

PVGLB_HSV1P

828-890

PVGLF_SV41

144-185

241-269

459-496

PVGLB_HSV23

828-890

PVGLF_SV5

137-171

417-444

PVGLB_HSV2H

828-890

PVGLF_TRTV

124-161

193-200

457-484

PVGLB_HSV2S

817-871

PVGLG_BEFV

523-557

PVGLB_HSV6U

37-71

165-223

PVGLG_BRSVC

92-123

PVGLB_HSVB1

859-913

PVGLG_HRSV1

63-93

PVGLB_HSVB2

440-474

848-902

PVGLG_HRSV4

66-107

PVGLB_HSVBC

863-900

PVGLG_HRSV5

243-273

PVGLB_HSVE1

642-678

911-961

PVGLG_HRSV8

66-93

PVGLB_HSVE4

474-515

847-900

PVGLG_HSVE4

271-298

PVGLB_HSVEA

542-676

911-961

PVGLG_HSVEB

383-410

PVGLB_HSVEB

542-676

911-961

PVGLG_RABVT

489-519

PVGLB_HSVEL

642-678

910-960

PVGLG_VSVIG

472-499

PVGLB_HSVMD

390-435

649-683

787-845

PVGLH_EBV

649-676

619-648

PVGLB_HSVSA

240-288

406-447

PVGLH_HCMVA

107-136

270-297

PVGLB_MCMV6

208-260

427-476

693-778

860-894

PVGLH_HCMVT

106-135

PVGLB_PRVIF

847-881

PVGLH_HSV6G

82-89

360-403

PVGLB_VZVD

92-133

596-630

809-867

PVGLH_HSVSA

388-416

PVGLC_HSV11

469-510

PVGLI_HCMVA

47-111

PVGLC_HSV1K

469-510

PVGLM_BUNGE

512-546

914-941

1128-1255

PVGLC_HSV2

442-476

PVGLM_BUNL7

913-950

PVGLC_HSV23

443-477

PVGLM_BUNYW

340-374

504-535

662-709

PVGLC_HSVBC

235-269

PVGLM_DUGBV

945-972

PVGLC_HSVEB

182-218

PVGLM_HANTB

73-100

693-720

PVGLC_HSVMB

63-97

PVGLM_HANTH

75-102

PVGLC_HSVMG

62-96

PVGLM_HANTL

75-102

PVGLC_HSVMM

63-97

PVGLM_HANTV

75-102

PVGLC_PRVIF

183-235

PVGLM_PHV

69-96

PVGLC_VZVD

280-321

PVGLM_PUUMH

72-110

PVGLC_VZVS

280-321

PVGLM_PUUMS

72-110

PVGLD_HSVEA

89-123

PVGLM_SEOUR

73-100

513-540

694-721

PVGLD_HSVEB

139-173

PVGLM_SEOUS

73-100

513-540

894-721

PVGLD_HSVEK

139-173

PVGLN_BEFV

523-584

PVGLE_HSV11

111-145

PVGLP_BEV

48-82

1145-1179

1184-1211

1505-1532

PVGLE_HSV2

111-159

PVGLX_HSVEB

17-44

413-444

PVGLF_BRSVA

146-202

804-545

PVGLX_PRVRI

427-481

PVGLF_BRSVC

146-202

267-302

506-547

PVGLY_JUNIN

14-41

PVGLF_BRSVR

146-202

267-302

505-554

PVGLY_LASSG

86-113

PVGLF_CDVO

228-297

340-381

568-602

PVGLY_MOPEI

86-113

316-346

PVGLF_HRSV1

118-203

267-302

506-549

PVGLY_PIARV

334-375

PVGLF_HRSVA

116-202

267-302

506-549

PVGLV_TACV

109-138

315-350

PVGLF_HRSVL

116-202

267-302

506-547

PVGLY_TACV5

303-338

PVGLF_HRSVR

116-202

267-302

506-549

PVGLY_TACV7

302-337

PVGLF_MEASE

116-184

228-269

452-500

PVGLY_TACVT

303-338

PVGLF_MEASI

119-187

231-272

455-503

PVGLZ_HSVEK

17-44

PVGLF_MEASY

116-184

228-269

452-500

PVGNM_BPMV

403-430

PVOLF_MUMPM

20-54

103-179

235-272

447-502

PVGNM_CPSMV

192-221

PVGLF_MUMPR

20-54

103-179

235-272

447-502

PVGP8_EBV

104-149

PVGLF_MUMPS

20-54

103-179

235-272

447-502

PVM1_REOVL

290-317

PVGLF_NDVA

117-182

231-272

426-512

PVM21_REOVD

625-662

PVGLF_NDVS

122-182

231-272

426-517

PVM22_REOVD

624-661

PVGLF_NDVI

133-182

236-272

426-517

PVM2_REOVJ

624-881

PVGLF_NDVM

117-182

231-272

426-512

PVM3_REOVD

169-186

343-370

450-483

631-690

PVGLF_NDVT

117-182

231-272

426-517

PVMA2_BRSVA

124-152

PVGLF_NDVTG

122-182

231-272

425-517

PVMA2_HRSVA

124-151

PVGLF_NDVU

122-182

231-272

426-512

PVMAT_BRSVA

219-248

PVGLF_PHODV

29-63

197-266

309-350

533-581

PVMAT_HRSVA

219-248

PVGLF_PI1HC

123-174

207-267

459-503

PVMAT_INCJJ

151-185

PVGLF_PI2H

93-183

477-528

PVMAT_NDVA

247-274

PVGLF_PI2HG

93-183

477-528

PVMAT_PI2HT

96-123

PVGLF_PI2HT

93-185

477-528

PVMAT_PI3B

201-231

PVGLF_PI3B

117-182

207-241

456-518

PVMAT_PI3H4

201-231

PVGLF_PI3H4

117-182

207-241

462-532

PVMAT_SV41

323-353

PVGLF_RINDK

112-180

224-265

448-493

PVME1_CVBM

175-209

PVGLF_RINDL

112-180

224-265

448-508

PVME1_CVTKE

175-209

PVGLF_SEND5

127-188

211-271

463-533

PVME1_IBV6

21-48

184-218

PVGLF_SENDF

127-188

211-271

463-533

PVME1_IBVB

21-48

184-218

PVGLF_SENDH

127-188

218-271

463-533

PVME1_IBVB2

21-48

184-218

PVGLF_SENDJ

127-188

211-271

463-533

PVME1_IBVK

184-218

PVGLF_SENDZ

127-188

211-271

463-533

PVMP_CAMVC

220-254

273-324

PVGLF_SV41

96-188

454-508

PVMP_CAMVD

29-56

220-254

273-324

PVGLF_SV5

103-171

241-275

451-487

PVMP_CAMVE

227-254

273-324

PVGLF_TRTV

105-161

190-224

457-498

PVMP_CAMVN

220-254

273-324

PVGLG_BEFV

506-812

PVMP_CAMVS

220-254

273-324

PVGLG_BRSVC

30-70

104-138

PVMP_CAMVW

220-254

273-324

PVGLG_HRSV1

30-81

PVMP_CERV

26-53

100-127

PVGLG_HRSV2

30-85

PVMP_SOCMV

4-31

78-118

PVGLG_HRSV3

30-85

PVMSA_HPBHE

294-328

PVGLG_HRSV4

30-107

PVMT1_DHVI1

38-65

237-284

PVGLG_HRSV5

30-85

PVMT8_MYXVL

163-190

PVGLG_HRSV6

30-85

PVMT9_MYXVL

465-492

PVGLG_HRSV7

30-85

PVGLG_HRSV8

30-81

PVGLG_HRSVA

30-67

PVGLG_HRSVL

25-85

PVGLG_HSVE4

271-306

PVGLG_SIGMA

344-381

484-498

PVGLG_SYNV

488-523

PVGLG_VHSVO

363-397

PVGLG_VSVIG

476-510

PVGLH_EBV

53-87

160-201

336-380

653-694

PVGLH_HCMVA

103-137

270-311

893-741

PVGLH_HCMVT

102-136

692-740

PVGLH_HSV11

447-481

PVGLH_HSV1E

447-481

PVGLH_HSVBG

357-406

PVGLH_HSVBC

364-416

PVGLH_HSVE4

334-379

414-455

PVGLH_HSVEB

327-372

407-448

PVGLH_HSVSA

32-88

374-453

664-712

PVGLH_MCMVS

440-474

PVGLH_PRVKA

226-260

PVGLH_PRVN3

226-260

PVGLH_PRVRI

226-260

PVGLH_VZVD

455-506

PVGLI_HCMVA

47-111

323-359

PVGLM_BUNGE

512-567

685-737

1228-1262

PVGLM_BUNL7

643-677

916-950

PVGLM_BUNSH

643-677

PVGLM_BUNYW

340-374

504-563

905-939

PVGLM_DUGBV

937-989

1239-1300

PVGLM_HANTB

693-727

PVGLM_HANTH

72-106

PVGLM_HANTL

72-106

PVGLM_HANTV

72-108

PVGLM_PHV

73-111

PVGLM_PTPV

149-251

PVGLM_SEOUR

694-728

PVGLM_SEOUS

693-730

PVGLN_BEFV

377-414

513-569

PVGLP_BEV

43-82

90-124

622-856

1128-1236

PVGLX_HSVEB

177-262

PVGLX_PRVRI

420-461

PVGLY_JUNIN

301-349

PVGLY_LASSG

317-360

388-422

PVGLY_LASSJ

316-361

389-423

PVGLY_LYCVA

333-367

395-432

PVGLY_LYCVW

124-158

333-367

395-432

PVGLY_MOPEI

316-359

PVGLY_PIARV

334-375

PVGLY_TACV

315-363

PVGLY_TACV5

303-351

382-416

PVGLY_TACV7

302-350

381-415

PVGLY_TACVT

303-351

382-416

PVGNB_CPMV

835-869

PVGNM_BPMV

143-177

403-437

PVGNM_CPMV

160-201

PVGNM_CPSMV

192-226

758-792

674-915

PVGNM_RCMV

837-871

912-946

PVGP8_EBV

94-149

PVM01_VACCC

5-56

PVM1_REOVL

287-321

PVM21_REOVD

416-450

619-663

PVM22_REOVD

416-450

618-662

PVM2_REOVJ

416-450

618-662

PVM2_REOVL

416-450

618-662

PVM3_REOVD

135-190

337-371

623-558

618-690

PVMA2_BRSVA

42-90

PVMA2_HRSVA

42-90

PVMAT_CDVO

193-234

PVMAT_INCJJ

73-114

151-208

PVMAT_NDVA

310-359

PVMAT_NDVB

324-358

PVMAT_PI3B

99-133

204-252

PVMAT_PI3H4

99-133

204-252

PVMAT_RABVA

69-103

PVMAT_RABVC

69-103

PVMAT_RABVE

69-103

PVMAT_RABVN

69-103

PVMAT_RABVP

69-103

PVMAT_RASVS

69-103

PVMAT_SYNV

246-280

PVMAT_VSVIG

198-232

PVME1_CVBM

175-209

PVME1_CVPFS

98-140

212-267

PVME1_CVPPU

212-257

PVME1_CVPRM

212-257

PVME1_CVTKE

28-62

175-209

PVME1_FIPV

212-267

PVME1_IBV6

21-55

177-218

PVMEI_IBVB

21-55

177-218

PVME1_IBVB2

21-55

177-218

PVME1_IBVK

36-94

PVMP_CAMVC

187-254

270-324

PVMP_CAMVD

187-254

270-324

PVMP_CAMVE

187-254

270-324

PVMP_CAMVN

187-254

270-324

PVMP_CAMVS

187-254

270-324

PVMP_CAMVW

187-254

270-324

PVMP_CERV

212-246

PVMP_FMVD

217-251

PVMP_SOCMV

76-118

PVMSA_HPBDB

272-313

324-361

PVMSA_HPBOC

271-312

323-360

PVMSA_HPBDU

234-275

289-323

PVMSA_HPBOW

272-313

324-361

PVMSA_HPBGS

210-244

PVMSA_HPBHE

294-328

PVMSA_WHV1

208-242

PVMSA_WHV59

213-247

PVMSA_WHV7

213-247

PVMSA_WHVBI

213-247

PVMT1_DHVI1

201-235

PVMT1_IAANN

92-126

174-222

PVMT1_IABAN

92-126

174-222

PVMT1_IACAO

31-79

PVMT1_IAFOW

92-126

174-222

PVMT1_IAFPR

92-126

174-222

PVMT1_IAFPW

92-126

174-222

PVMT1_IALE1

92-126

174-222

PVMT1_IALE2

92-126

174-222

PVMT1_IAMAN

92-126

174-222

PVMT1_IAPOC

92-126

174-222

PVMT1_IAPUE

92-126

174-222

PVMT1_IAUDO

92-126

174-222

PVMT1_IAWIL

92-126

174-222

PVMT1_IAZI1

92-126

174-222

PVMT1_INBAC

175-209

PVMT1_INBAD

175-209

PVMT1_INBLE

175-209

PVMT1_INBSI

175-209

PVMT2_INBAC

132-184

PVMT2_INBAD

132-184

PVMT2_INBLE

132-184

PVMT2_INBSI

132-184

PVMT8_MTXVL

46-80

145-197

TABLE VI

Search Results Summary for PCTLZIP, P1CTLZIP, and P2CTLZIP Motifs

PCTLZIP

P1CTLZIP

P2CTLZIP

LIBRARY FILE

LIBRARY FILE

LIBRARY FILE

PENV_FOAMV

481-496

PENV_BIVO6

434-450

PENV_BIVO6

526-542

PENV_HV1MA

438-453

PENV_BIV27

463-479

PENV_BIV27

554-571

PENV_HV1MP

163-188

PENV_FOAMV

481-496

864-880

PENV_FENV1

30-47

630-647

PENV_HVIRH

445-480

PENV_HV1KB

762-788

PENV_FIVPE

781-798

PEMV_HV18C

188-201

PENV_HV1MA

437-453

PENV_FIVSD

779-798

PENV_HVIZ2

123-138

PENV_HV1MP

183-199

PENV_FIVT2

780-797

PENV_HVIZH

438-453

PENV_HV1RH

444-460

PENV_FRVC6

38-55

824-841

PENV_HV28E

750-785

PENV_HV1S1

738-754

PENV_FLVGL

806-822

PENV_HV2D1

741-758

PENV_HVISC

168-201

PENV_FLVLB

825-842

PENV_HV231

741-758

PENV_HV1Z2

123-138

PENV_FLVSA

802-619

PENV_HV2NZ

742-757

PENV_HV1Z3

117-133

PENV_FOAMV

710-727

967-974

PENV_HV2RO

751-766

PENV_HVIZH

437-453

PENV_FSVGA

825-642

PENV_HV2S8

743-758

PENV_HV2BE

750-765

PENV_FSVGB

806-822

PENV_HV2ST

745-780

PENV_HV2D1

741-758

PENV_FBVSM

608-625

PENV_JSRV

104-119

PENV_HV2G1

741-758

PENV_HV1OY

123-140

PENV_MMTVB

618-633

PENV_HV2NZ

742-767

PENV_HV1Z2

410-427

PENV_MMTVG

618-633

PENV_HV2RO

751-788

PENV_HV1Z3

154-171

PENV_SIVMK

139-154

PENV_HV2S8

743-758

PENV_HV2CA

750-787

PENV_SIVML

139-154

PENV_HV2ST

745-760

PENV_MCFF

600-617

PHEMA_CVBLY

391-408

PENV_JSRV

104-119

541-567

PENV_MCFF3

601-618

PHEMA_CVBM

391-408

PENV_MCFF

397-413

PENV_MLVAV

630-647

PHEMA_CVSQ

391-408

PENV_MCFF3

397-413

PENV_MLVCB

626-642

PHEMA_CVHOC

391-408

PENV_MLVAV

427-443

PENV_MLVF5

639-656

PHEMA_CVMA5

402-417

PENV_MLVCB

423-438

PENV_MLVFF

639-656

PHEMA_CVMS

403-418

PENV_MLVHO

424-440

PENV_MLVFP

639-656

PHEMA_INBAA

295-310

PENV_MLVMO

426-442

PENV_MLVNO

626-643

PHEMA_INBBE

303-318

PENV_MLVRD

424-440

PENV_MLVKI

167-164

PHEMA_INBBO

293-309

PENV_MLVRK

424-440

PENV_MLVMO

629-646

PHEMA_INBEN

301-318

PENV_MMTVB

816-833

PENV_MLVRD

624-641

PHEMA_INBFU

288-301

PENV_MMTVG

618-633

PENV_MLVRK

624-641

PHEMA_INBGL

286-311

PENV_SFV1

884-880

PENV_MSVFB

170-187

PHEMA_INBHK

293-308

PENV_SFV3L

881-577

PENV_RMCFV

603-620

PHEMA_INBIB

266-303

PENV_SIVGB

93-109

PENV_SPV1

710-727

957-974

PHEMA_INBID

299-314

PENV_SIVMK

139-154

802-818

PENV_SFV3L

707-724

954-971

PHEMA_INBLE

302-317

PENV_SIVML

139-154

801-817

PENV_SIVM1

766-783

PHEMA_INBMD

292-307

PENV_SIVS4

808-822

PENV_SIVMK

765-782

PHEMA_INBME

298-311

PENV_SIVBP

810-826

PENV_SWML

764-781

PHEMA_INBNA

288-303

PHEMA_CDVO

38-62

PENV_SIVS4

769-786

PHEMA_INBOR

301-318

PHEMA_CVBLY

391-408

PENV_SIVSP

773-790

PHEMA_INBSI

301-318

PHEMA_CVBM

391-408

PENV_SMRVH

638-553

PHEMA_INSBJ

299-313

PHEMA_CVBQ

391-408

PENV_SMSAV

42-69

PHEMA_INBUS

294-309

PHEMA_CVHOC

391-408

PHEMA_CDVO

38-53

200-217

PHEMA_INBVI

296-311

PHEMA_CVMA6

402-417

PHEMA_CVBLV

391-408

PHEMA_INBVK

303-318

PHEMA_CVMS

403-418

PHEMA_CVSM

391-408

PHEMA_INBYB

286-301

PHEMA_IAAIC

237-253

PHEMA_CVBQ

391-408

PHEMA_MUMPM

133-148

PHEMA_IABAN

221-237

PHEMA_CVHOC

391-408

PHEMA_MUMPR

133-148

PHEMA_IABUD

234-250

PHEMA_IAAIC

322-339

PHEMA_MUMPS

133-148

PHEMA_IACKA

234-250

PHEMA_IABAN

320-323

PHEMA_PIHW

345-380

PHEMA_IACKG

231-247

PHEMA_IABUD

320-337

PHEMA_PI2N

65-80

PHEMA_IACKV

230-248

PHEMA_IACKA

320-337

PHEMA_PI2HT

65-80

PHEMA_IADA1

234-250

PHEMA_IACKG

316-333

PHEMA_RINDK

366-383

PHEMA_IADA3

237-253

PHEMA_IACKP

302-319

PHEMA_SV5

7-94

PHEMA_IADCZ

234-250

PHEMA_IACKQ

302-319

PHEMA_SV5CM

7-94

PHEMA_IADH1

221-237

PHEMA_IACKS

319-336

PHEMA_SV5CP

7-94

PHEMA_IADH2

221-237

PHEMA_IACKV

315-332

PHEMA_SV5LN

7-94

PHEMA_IADH3

221-237

PHEMA_IADA1

320-337

PVENV_DHVI1

42-57

PHEMA_IADH4

221-237

PHEMA_IADA3

322-339

PVFP7_CAPVK

89-104

PHEMA_IADH5

221-237

PHEMA_IADCZ

320-337

PVFUS_VACC6

72-87

PHEMA_IADH6

221-237

PHEMA_IADH1

306-323

PVGOI_BPP22

242-257

PHEMA_IADH7

221-237

PHEMA_IADH2

306-323

PVGO1_HSVEB

169-184

PHEMA_IADM2

237-253

PHEMA_IAOH3

306-323

PVGQ1_HSVI1

210-226

317-332

PHEMA_IADNZ

234-250

PHEMA_IADN4

306-323

PV006_BPT4

184-199

PHEMA_IAEN6

221-237

PHEMA_IADH6

306-323

PVOD7_BPT4

885-900

PHEMA_IAEN7

237-253

PHEMA_IADN7

306-323

PVGOS_HSVI1

134-149

PHEMA_IAFPR

230-248

PHEMA_IADM2

322-339

PVGIO_BPPH2

183-196

PHEMA_IAHAL

236-252

PHEMA_IADMZ

320-337

PVG1O_BPPZA

183-196

PHEMA_IANAR

235-251

PHEMA_IADU3

322-339

PVGIO_HSVSA

109-124

PHEMA_IAHC8

230-246

PHEMA_IAEN6

306-323

PVG16_BPP1

81-96

PHEMA_IAHC7

230-246

PHEMA_IAEN7

322-339

PVG18_BPT4

463-483

PHEMA_IAHCD

230-246

PHEMA_IAFPR

315-332

PVG2S_BPT4

97-112

PHEMA_IAHDE

230-246

PHBMA_IAGRE

320-337

PVG29_HSVI1

20-35

PHEMA_IAHFO

236-252

PHEMA_IAGU2

320-337

PVG3O_BPPH6

11-94

PHEMA_IAHK6

236-252

PHEMA_IAGUA

319-336

PVG3O_BPOX2

22-37

PHEMA_IAHK7

236-252

PHEMA_IAHAL

321-338

PVG36_NBVSA

108-123

PHEMA_IAHLE

230-246

PHEMA_IAHC6

315-332

PVG37_BPT2

1253-1268

PHEMA_IAHLO

230-246

PHEMA_IAHC7

315-332

PVG37_HBVI1

284-299

PHEMA_IAHMI

236-252

PHEMA_IAHCD

315-332

PVG55_HSVI1

22-37

143-158

PHEMA_IAHNM

236-252

PHEMA_IAHDE

315-332

PVGS6_HSVI1

268-283

PHEMA_IANRO

236-252

PHEMA_IAHFO

321-338

PVGS8_HSVI1

102-117

PHEMA_IAHSA

236-252

PHEMA_IAHK6

321-338

PVG59_HSVI1

267-292

PHEMA_IAHSP

230-246

PHEMA_IAHK7

321-339

PVG65_HSVI1

518-533

PHEMA_IAHSW

230-246

PHEMA_IAHLE

315-332

PVG9_BPPH2

234-279

PHEMA_IAHTE

236-252

PHEMA_IAHLO

316-332

PVG9_BPPZA

234-279

PHEMA_IAHTO

236-252

PHEMA_IAHMI

321-338

PVG9_SPV1R

57-72

PHEMA_IAHUR

236-252

PHEMA_IAHNM

321-338

PVGF_BPPHX

234-249

PHEMA_IAKIE

235-251

PHEMA_IAHNN

315-332

PVGL2_CVBF

264-279

PHEMA_IALEN

235-251

PHEMA_IANPR

315-332

PVGL2_CVBL9

264-279

PHEMA_IAMAA

233-249

PHEMA_IAHRO

321-338

PVGL2_CVBLY

264-279

PHEMA_IAMAB

236-254

PHEMA_IANSA

321-338

PVGL2_CVBM

264-279

PHEMA_IAMAO

237-253

PNEMA_IANSP

315-332

PVGL2_CVBQ

264-279

PHEMA_IAME1

237-253

PHEMA_IANSW

315-332

PVGL2_CVBV

264-279

PHEMA_IAME2

237-253

PHEMA_IANTE

321-339

PVGL2_CVPFS

442-467

PHEMA_IAMEG

221-237

PHEMA_IAHTO

321-339

PVGL2_CVPPU

440-465

504-519

PHEMA_IAMIN

85-101

231-247

PHEMA_IAHUR

321-339

PVGL2_CVPRB

218-233

PHEMA_IANT8

237-263

PHEMA_IAJAP

317-334

PVGL2_CVPRM

218-233

PHEMA_IAOU7

221-237

PHEMA_IAMAA

319-338

PVGL2_IBV8

1056-1071

PHEMA_IARUD

234-250

PHEMA_IAMAB

324-341

PVGL2_IBVB

1055-1070

PHEMA_IASE2

234-250

PHEMA_IAMAO

322-339

PVGL2_IBVD2

1058-1071

PHEMA_IASH2

234-250

PHEMA_IAME1

322-339

PVGL2_IBVK

1055-1070

PHEMA_IASTA

230-246

PHEMA_IAME2

322-339

PVGL2_IBVM

1055-1070

PHEMA_IATAI

235-251

PHEMA_IAME8

308-323

PVGLB_HSVSA

701-718

PHEMA_IATKM

234-250

PHEMA_IAMIN

306-333

PVGLB_PRVIF

203-216

PHEMA_IATKO

233-249

PHEMA_IANT8

322-339

PVGLC_MSVBC

475-490

PHEMA_IATKR

230-246

PMEMA_IAPIL

320-337

PVGLC_HSVE4

444-469

PHEMA_IATKW

229-245

PHEMA_IAQU7

338-323

PVGLC_HSVEB

427-442

PHEMA_IAUDO

237-253

PHEMA_IARUD

320-337

PVGLC_PRVIF

448-461

PHEMA_IAUSS

236-251

PHEMA_IASE2

320-337

PVGLD_HSV11

79-94

PHEMA_IAVI7

238-264

PHEMA_IASH2

321-338

PVGLF_HSV2

79-94

PHEMA_IAXIA

235-251

PHEMA_IASTA

315-332

PVGLF_BRSVA

265-280

PHEMA_IAZCO

237-263

PHEMA_IATKM

320-337

PVGLF_BRSVC

265-280

PHEMA_IAZH2

221-237

PHEMA_IAUDO

322-339

380-397

PVGLF_BRSVR

265-280

PHEMA_IAZH3

221-237

PHEMA_IAVI7

323-340

PVGLF_HRSV1

265-280

PHEMA_IAZUK

237-253

PHEMA_IAZCO

322-339

PVGLF_HRSVA

265-280

PHEMA_INBAA

115-131

295-310

PHEMA_IAZH2

306-323

PVGLF_HRSVL

265-280

PHEMA_INBBE

123-139

303-316

PHEMA_IAZH3

306-323

PVGLF_HRSVR

265-280

PHEMA_INBBO

118-132

293-308

PHEMA_IAZUK

322-339

PVGLF_MUMPS

5-94

PHEMA_INBEN

123-139

301-318

PHEMA_MUMPM

101-118

PVGLF_VZVD

279-293

PHEMA_INBFU

109-124

286-301

PHEMA_MUMPR

101-118

PVGLM_HANTB

900-915

PHEMA_INBGL

119-135

268-311

PHEMA_MUMPS

101-118

PVGLM_PTPV

743-758

PHEMA_INBHK

118-132

293-306

PHEMA_NDVA

93-110

PVGLM_SEOUR

901-918

PHEMA_INBIB

108-124

289-303

PHEMA_NDVB

93-110

PVGLM_SEOUS

900-916

PHEMA_INBID

120-138

299-314

PHEMA_NDVD

93-110

PVGLY_LASGG

428-441

PHEMA_INBLE

123-139

302-317

PHEMA_NDVH

93-110

PVGLY_LASSJ

427-442

PHEMA_INBMD

113-129

292-307

PHEMA_NDVI

93-110

PVGLY_MOPEI

425-440

PHEMA_INBME

116-132

296-311

PHEMA_NDVM

93-110

PVM3_REOVD

521-538

PHEMA_INBNA

108-124

288-303

PHEMA_NDVQ

93-110

PVMSA_HPSG8

380-396

PHEMA_INBOR

123-139

301-316

PHEMA_NDVTG

93-110

PVMSA_HPBV9

187-202

PHEMA_INBSI

123-139

301-316

PHEMA_NDVU

93-110

PVMSA_WHV1

378-393

PHEMA_INBSJ

119-135

298-313

PHEMA_PHODV

38-53

PVMSA_WHV59

383-398

PHEMA_INBUS

116-132

294-309

PHEMA_PI1HW

486-503

PVMSA_WHV7

383-398

PHEMA_INBVI

116-132

298-311

PHEMA_PI3B

111-128

PVMSA_WHV8

383-398

PHEMA_INBVK

123-139

303-318

PHEMA_PI3H4

111-128

PVMSA_WHV8I

383-398

PHEMA_INBYB

108-124

280-301

PHEMA_PI3HA

111-128

PVMSA_WHVW8

234-249

PHEMA_MUMPM

133-148

PHEMA_PI3HT

111-128

PVMT2_IAANN

25-40

PHEMA_MUMPR

133-148

PHEMA_PI3HU

111-128

PVMT2_IABAN

25-40

PHEMA_MUMPS

133-148

PHEMA_PI3HV

111-128

PVMT2_IAFOW

25-40

PHEMA_PI1HW

345-380

PHEMA_PI3HW

111-128

PVMT2_IAFPR

25-40

PHEMA_PI2H

65-81

PHEMA_PI3HX

111-128

PVMT2_IAFPW

25-40

PHEMA_PI2HT

65-81

PHEMA_PI4HA

50-87

PVMT2_IALE1

25-40

PHEMA_PI3B

324-340

PHEMA_SV41

85-102

PVMT2_LALE2

25-40

PHEMA_PI3H4

324-340

PHEMA_SV5

84-101

PVMT2_IAMAN

25-40

PHEMA_PI3HA

324-340

PHEMA_SV5CM

84-101

PVMT2_IAPUE

25-40

PHEMA_PI3HT

324-340

PHEMA_SV5CP

84-101

PVMT2_IASIN

25-40

PHEMA_PI3HU

324-340

PHEMA_SV5LN

84-101

PVMT2_IAUDO

25-40

PHEMA_PI3HV

324-340

PVFDS_VACCC

280-297

PVMT2_IAWIL

25-40

PHEMA_PI3HW

324-340

PVVDB_VACCP

280-297

PVMT2_MYXVL

228-241

PHEMA_PI3HX

324-340

PVFOS_VACCV

281-298

PHEMA_RINDK

380-383

PVFO9_VACCC

176-193

PHEMA_BV5

7-94

PVFD9_VACCV

176-193

PHEMA_SV5CM

7-94

PVG27_HSVSA

209-226

PHEMA_SV5CP

7-94

PVG2S_H8VI1

173-190

PHEMA_SV5LH

7-94

PVG39_HSVI1

648-686

PVENV_DHVI1

42-57

PVG43_H8VI1

109-128

521-536

PVENV_EAV

25-41

PVG87_HSVI1

171-188

PVFP2_FOWPV

88-104

PVG72_HSVI1

1252-1289

PVFP7_CAPVK

89-104

PVGF1_HBVB

3073-3090

PVFUS_VACC6

72-87

PVGLB_IBV6

1094-1111

PVGO1_HSVEB

169-184

PVGLB_HSVE1

738-753

PVGO1_HSVI1

209-225

317-332

PVGLB_HSVE4

675-892

PVGO8_HSVI1

134-149

PVGLB_HSVEA

738-753

PVG1O_HSVSA

109-124

PVGLB_HSVEB

738-753

PVG1I_HSVI1

103-119

PVGLB_HSVEL

738-753

PVG12_HSVI1

270-288

PVGLB_ILTV6

597-814

PVGI_SPV1R

76-92

PVGLB_ILTVS

807-824

PVG29_HSVI1

20-35

PVGLB_ILTVT

807-824

PVG3B_BPOX2

22-37

PVGLC_PRVIF

180-197

PVG3S_HSVSA

108-123

PVGLE_VZVD

489-498

PVG37_HSVI1

284-299

PVGL_SV5

401-418

PVG41_HSVI1

244-260

PVGLH_HCMVA

355-392

PVVG46_HSVI1

1244-1260

PVGLH_HCMVT

364-381

PVG55_HBVI1

22-37

143-158

PVGLH_HSV11

245-282

603-820

PVG56_HSVI1

268-283

PVGLH_HSV1E

245-282

603-820

PVG58_HSVI1

101-117

PVGLI_HSV11

43-80

PVG58_HSVSA

130-148

330-348

PVGLM_BUNL7

81-98

PVG59_HSVI1

267-282

PVGLM_BUNSH

81-98

PVG65_HSVI1

362-378

518-533

PVGLM_PUUMH

712-729

PVG71_HSVSA

89-105

PVGLM_PUUMS

712-729

PVG9_BPPN2

234-249

PVGLM_RVFV

344-381

PVG9_BPPZA

234-249

PVGLM_RVFVZ

344-381

PVG9_SPV1R

57-72

PVGLV_LASSG

12-94

PVGF1_IBVB

2210-2226

PVGLY_LASSJ

12-94

PVGL2_CVBF

123-139

174-190

264-279

PVGLV_LYCVA

12-94

PVGL2_CVBL9

123-139

174-190

264-279

PVGLY_LYCVW

12-94

PVGL2_CVBLY

123-139

174-190

264-279

PVGLY_MOPEI

12-94

PVGL2_CVBM

123-139

174-190

264-279

PVM1_REOVD

280-297

PVGL2_CVBQ

31-47

123-139

174-190

264-279

PVM1_REOVL

280-297

PVGL2_CVBV

123-139

174-190

264-279

PVMAT_COVO

148-185

PVGL2_CVM4

95-111

1267-1283

PVMAT_MEASI

187-104

PVGL2_CVMA5

95-111

1215-1231

PVMP_CAMVC

147-164

PVGL2_CVMJH

95-111

1126-1142

PVMP_CAMVD

147-164

PVGL2_CVPFS

442-457

800-816

1274-1290

PVMP_CAMVE

147-164

PVGL2_CVPPU

440-456

504-519

798-814

1272-1288

PVMP_CAMVN

147-164

PVGL2_CVPR8

218-233

576-592

1050-1066

PVMP_CAMVS

147-164

PVGL2_CVPRM

218-233

576-592

1050-1066

PVMP_CAMVW

147-164

PVGL2_FIPV

803-819

1277-1293

PVMSA_HPBVO

111 -94

PVGL2_IBV6

1056-1071

PVMSA_HPBV2

185-202

PVGL2_IBV8

1055-1070

PVMSA_HPBV4

185-202

PVGL2_IBVD2

1058-1071

PVMSAHPBVA

174-191

PVGL2_IBVK

1055-1070

PVMSA_HPBVD

11-94

PVGL2_IBVM

1055-1070

PVMSA_PBV1

174-191

PVGLS_HSVSA

701-718

PVMSA_HPBVL

174-197

PVGLS_PRVIF

203-218

PVMSA_HPBVN

11-94

PVGLB_VZVD

522-538

PVMSA_HPBVO

174-191

PVGLC_HSVBC

475-490

PVMSA_HPBVP

185-202

PVGLC_HSVE4

444-459

PVMSA_HPBVR

185-202

PVGLC_HSVEB

427-442

PVMSA_HPBVS

11-94

PVGLC_PRVIF

446-461

PVMSA_HPBVW

174-191

PVGLC_VZVD

150-165

PVMBA_HPBWY

174-191

PVGLC_VZVS

150-168

PVMSA_PSVZ1

174-191

PVGLD_HSV11

79-94

PVMT2_IAANN

25-42

PVGLD_HSV2

79-94

PVMT2_IABAN

25-42

PVGLE_PRVRI

3-94

PVMT2_IAFOW

25-42

PVGLF_BRSVA

205-221

265-280

PVMT2_IAFFR

25-42

PVGLF_BRBVC

205-221

265-280

PVMT2_IAFPW

25-42

PVGLF_BRSVR

205-221

265-280

PVMT2_IALEI

25-42

PVGLF_CDVO

398-414

PVMT2_IALE2

25-42

PVGLF_HRSVI1

205-221

265-280

PVMT2_IAMAM

25-42

PVGLP_HRSVA

205-221

265-280

PVMT2_IAPUE

25-42

PVGLF_HRBVL

205-221

265-280

PVMT2_IASIN

25-42

PVGLF_HRSVR

205-221

265-280

PVMT2_IAUDO

25-42

PVGLF_MEASE

286-302

PVMT2_IAWIL

25-42

PVGLF_MEASI

289-306

PVGLF_MEASY

286-302

PVGLF_MUMPM

276-292

PVGLF_MUMPR

276-292

PVGLF_MUMPS

5-94

278-292

PVGLF_NDVA

273-289

PVGLP_NDVS

273-289

PVGLP_NDVM

273-289

PVGLP_NDVT

273-289

PVGLF_NDVTG

273-289

PVGLF_NDVU

273-289

PVGLP_PHODV

269-285

387-383

PVGLF_RINDK

282-298

PVGLF_RINDL

282-298

PVGLF_TRTV

175-191

PVGLI_VZVD

276-293

PVGLM_HANTB

355-371

900-915

PVGLM_HANTH

499-515

PVGLM_HANTL

499-515

PVGLM_HANTV

499-515

PVGLM_PTPV

743-758

PVGLM_PUUMH

509-525

PVGLM_PUUMS

509-525

PVGLM_SEOUR

355-371

901-916

PVGLM_SEOUS

355-371

900-915

PVGLM_UUK

826-842

PVGLP_BEV

669-886

PVGLY_LASSG

12-94

428-441

PVGLY_LASSJ

12-94

427-442

PVGLY_LYCVA

12-94

PVGLY_LVCVW

12-94

PVGLY_MOPEI

12-94

425-440

PVGLY_PIARV

12-94

PVGNM_CPMV

1021-1037

PVM3_REOVD

521-530

PVMAT_MUMPS

191-207

PVMAT_NDVA

135-151

PVMAT_NDVB

135-151

PVMAT_PI2HT

189-206

PVMAT_SV41

189-206

PVMAT_SV6

98-114

132-148

PVMP_CAMVC

118-134

PVMP_CAMVD

118-134

PVMP_CAMVE

118-134

PVMP_CAMVN

118-134

PVMP_CAMVS

118-134

PVMP_CAMVW

118-134

PVMP_FMVD

115-131

PVMSA_HPBGS

380-396

PVMSA_HPBV9

187-202

PVMSA_WHV1

378-393

PVMSA_WHV59

383-398

PVMSA_WHV7

383-398

PVMSA_WHV8

383-398

PVMSA_WHV8I

383-398

PVMSA_WHVW6

234-249

PVMT2_IAANN

25-40

PVMT2_IABAN

25-40

PVMT2_IAFOW

25-40

PVMT2_IAFPR

25-40

PVMT2_IAFPW

25-40

PVMT2_IALE1

25-40

PVMT2_IALE2

25-40

PVMT2_IAMAN

25-40

PVMT2_IAPUE

25-40

PVMT2_IASIN

25-40

PVMT2_IAUDO

25-40

PVMT2_IAWIL

25-40

PVMT9_MYXVL

226-241

TABLE VII

Search Results Summary for P3CTLZIP, P4CTLZIP,

P5CTLZIP, and P6CTLZIP Motifs

P3CTLZIP

P4CTLZIP

P5CTLZIP

P6CTLZIP

LIBRARY FILE

LIBRARY FILE

LIBRARY FILE

LIBRARY FILE

PENV_BIV27

147-165

PENV1_FRSFV

380-399

PENV1_FRSFV

380-400

PENV_BIV06

47-68

625-546

PENV_CAEVC

810-828

PENV_AVISU

98-117

PENV2_FRSFV

380-400

PENV_BIV27

47-68

147-168

564-575

PENV_CAEVG

808-826

PENV_BIV27

147-166

PENV_BAEVM

170-190

PENV_FENV1

225-246

630-651

PENV_HV2BE

750-768

PENV_HV1ZH

123-142

PENV_FIVPE

781-801

PENV_FLVC6

624-645

PENV_HV2D1

741-759

PENV_HV2D2

9-29

PENV_FIVSD

779-799

PENV_FLVGL

447-468

605-626

PENV_HV2G1

741-759

PENV_HV2SB

778-797

PENV_FIVT2

780-800

PENV_FLVLB

467-488

625-646

PENV_HV2NZ

742-760

PENV_JSRV

541-560

PENV_FLVGL

9-29

PENV_FLVSA

444-465

602-623

PENV_HV2RO

751-769

PENV_RSVP

533-552

PENV_FOAMV

255-275

924-944

PENV_FOAMV

153-174

957-978

PENV_HV2SB

743-761

PHEMA_VACCC

173-192

PENV_FSVGA

9-29

PENV_FSVGA

467-488

625-646

PENV_HV2ST

745-763

PHEMA_VACCI

173-192

PENV_HV1C4

428-448

PENV_FSVGB

447-468

605-626

PENV_JSRV

376-394

PHEMA_VACCT

173-192

PENV_HV2CA

750-770

PENV_FSVSM

450-471

608-629

PHEMA_PI2H

118-136

PHEMA_VACCV

173-192

PENV_MLVF5

400-420

PENV_FSVST

467-488

PHEMA_PI2HT

118-136

PVENV_BEV

62-81

PENV_MMTVB

643-663

PENV_GALV

52-73

519-540

PHEMA_6V41

55-73

PVENV_MCV1

61-80

PENV_MMTVG

643-663

PENV_HV2BE

750-771

PVENV_THOGV

473-491

PVENV_MCV2

61-80

PENV_OMVVS

75-95

PENV_HV2G1

741-782

PVG16_BPP22

83-101

PVFUS_ORFNZ

29-48

PENV_RSVP

42-62

PENV_HV2NZ

742-763

PVG24_BPT4

115-133

PVG01_HSVEB

169-188

PENV_SFV1

924-944

PENV_HV2RO

751-772

PVG36_HSVSA

344-362

PVG01_VACCC

376-395

PENV_SFV3L

921-941

PENV_HV2ST

745-766

PVG40_HSVI1

14-32

PVG01_VACCV

315-334

PENV_SIVM1

766-786

PENV_MCFF

600-621

PVG50_HSVSA

5-94

PVG01_VARV

376-395

PENV_SIVMK

765-785

PENV_MCFF3

601-622

PVG51_BPT4

63-81

PVG06_BPT4

627-646

PENV_SIVML

764-784

PENV_MLVAV

630-651

PVG51_HSVI1

84-102

PVG10_HSVI1

35-54

PENV_SIVS4

769-789

PENV_MLVCB

625-646

PVG65_HSVI1

165-173

PVG11_HSVI1

103-122

150-169

PENV_SIVSP

773-793

PENV_MLVF5

639-660

PVGF1_IBVB

2788-2806

3374-3392

PVG1_BPPH2

31-50

PHEMA_CDVO

493-513

PENV_MLVFF

639-660

PVGL2_CVH22

1053-1071

PVG1_SPV1R

659-678

PHEMA_CVBLY

391-411

PENV_MLVFP

639-660

PVGL2_IBV6

1056-1074

PVG20_BPT4

231-250

PHEMA_CVBM

391-411

PENV_MLVHO

626-647

PVGL2_IBVB

1055-1073

PVG32_VZVD

90-109

PHEMA_CVBQ

391-411

PENV_MLVKI

167-188

PVGL2_IBVD2

1056-1074

PVG36_BPK3

132-151

PHEMA_CVHOC

391-411

PENV_MLVMO

629-650

PVGL2_IBVK

1055-1073

PVG37_BPT2

19-38

629-648

PHEMA_CVMA5

402-422

PENV_MLVRD

624-645

PVGL2_IBVM

1055-1073

PVG37_BPT4

19-38

625-644

PHEMA_IACKG

81-101

PENV_MLVRK

624-645

PVGLB_HSVB1

560-578

689-707

PVG39_HSVI1

1038-1057

PHEMA_IADMA

81-101

PENV_MSVFB

170-191

PVGLB_HSVBC

692-710

PVG41_HSVI1

62-81

PHEMA_MUMPM

397-417

PENV_RMCFV

603-624

PVGLB_HSVSA

584-602

PVG43_BPPF3

380-399

PHEMA_MUMPR

397-417

PENV_SFV1

957-978

PVGLB_ILTV6

740-758

PVG46_BPPF1

337-356

PHEMA_MUMPS

397-417

PENV_SFV3L

157-178

954-975

PVGLB_ILTVS

750-768

PVG59_HSVI1

142-161

PHEMA_PHODV

493-513

PENV_SIVAI

437-458

PVGLB_ILTVT

750-768

PVG61_HSVI1

117-136

PHEMA_PI1HW

322-342

PENV_SIVAG

442-463

PVGLC_VZVD

431-449

PVG67_HSVI1

318-337

1072-1091

PHEMA_PI2H

13-33

PENV_SIVA1

421-442

PVGLC_VZVS

431-449

PVGF1_IBVB

1587-1606

2108-2127

PHEMA_PI2HT

13-33

PENV_SIVAT

435-456

PVGLF_PI3H4

2-94

PVGL2_CVBF

991-1010

PHEMA_RINDL

497-517

PENV_SMSAV

42-63

PVGLH_HSV6G

314-332

PVGL2_CVBL9

991-1010

PHEMA_SEND5

322-342

PHEMA_CVMA5

402-423

PVGLH_HSVE4

814-832

PVGL2_CVBLY

991-1010

PHEMA_SENDF

322-342

PHEMA_IADE1

266-287

PVGLH_HSVEB

807-826

PVGL2_CVBM

991-1010

PHEMA_SENDH

322-342

PHEMA_MUMPM

225-246

PVGLI_HSV11

5-94

PVGL2_CVBQ

991-1010

PHEMA_SENDJ

322-342

PHEMA_MUMPR

225-246

PVGNM_BPMV

678-696

PVGL2_CVBV

991-1010

PHEMA_SENDZ

322-342

PHEMA_MUMPS

225-246

PVM01_VACCC

134-152

177-195

PVGL2_CVH22

768-787

1115-1134

PVENV_LELV

27-47

148-168

PHEMA_PHODV

213-234

PVM01_VACCV

83-101

126-144

PVGL2_CVM4

999-1018

PVENV_THOGV

356-376

PHEMA_PI2H

13-34

PVM1_REOVD

227-245

PVGL2_CVMA5

947-966

PVG01_VACCC

298-318

PHEMA_PI2HT

13-34

PVM1_REOVL

227-245

PVGL2_CVMJH

856-877

PVG01_VACCV

237-257

PHEMA_SV5

7-28

379-400

PVMAT_HRSVA

44-62

PVGL2_CVPFS

64-83

1038-1057

PVG01_VARV

298-318

PHEMA_SV5CM

7-28

379-400

PVMAT_NDVA

190-208

PVGL2_CVPPU

64-83

1036-1055

PVG06_VACCC

31-51

PHEMA_SV5CP

7-28

379-400

PVMAT_NDVB

190-208

PVGL2_CVPR8

814-833

PVG06_VARV

31-51

PHEMA_SV5LN

7-28

379-400

PVMP_CAMVC

183-201

PVGL2_CVPRM

814-833

PVG09_BPPF1

25-45

PVG01_HSVEB

169-190

PVMP_CAMVD

183-201

PVGL2_FIPV

1041-1060

PVG12_HSVI1

151-171

PVG01_HSVI1

589-610

PVMP_CAMVE

183-201

PVGL2_IBV6

588-607

771-790

PVG22_HSVI1

300-320

PVG23_HSVI1

314-335

PVMP_CAMVN

183-201

PVGL2_IBVB

587-606

770-789

PVG39_HSVI1

648-668

970-990

PVG37_BPOX2

65-86

PVMP_CAMVS

183-201

PVGL2_IBVD2

588-607

771-790

PVG51_HSVI1

29-49

PVG43_HSVI1

157-178

PVMP_CAMVW

183-201

PVGL2_IBVK

587-606

770-789

PVG63_HSVI1

336-356

PVG55_HSVI1

288-309

PVMP_FMVD

180-198

PVGL2_IBVM

587-606

770-789

PVG65_HSVI1

117-137

PVG55_HSVSA

85-106

PVGLB_HCMVA

706-725

PVG74_HSVSA

124-144

PVG56_HSVI1

1155-1176

PVGLB_HCMVT

707-726

PVGL2_IBV6

328-348

PVG58_HSVSA

266-287

PVGLB_HSV6U

117-136

PVGL2_IBVB

327-347

PVG60_HSVI1

30-51

PVGLB_ILTV6

256-275

PVGL2_IBVD2

328-346

PVG63_HSVI1

238-259

PVGLB_ILTVS

266-285

PVGL2_IBVD3

328-348

PVGF1_IBVB

1856-1877

PVGLB_ILTVT

266-285

PVGL2_IBVK

327-347

PVGH3_HCMVA

157-178

PVGLC_HSV11

3-94

467-486

PVGL2_IBVM

327-347

378-398

PVGL2_CVBF

1259-1280

PVGLC_HSV1K

3-94

467-486

PVGL2_IBVU2

310-330

PVGL2_CVBL9

1259-1280

PVGLC_HSVBC

475-494

PVGLB_EBV

732-752

PVGL2_CVBLY

1259-1280

PVGLG_CHAV

436-455

PVGLB_HCMVA

750-770

PVGL2_CVBM

1259-1280

PVGLG_RABVH

372-391

PVGLB_HCMVT

751-771

PVGL2_CVBQ

1259-1280

PVGLI_HSVEB

44-63

PVGLB_HSV23

79-99

PVGL2_CVBV

1259-1280

PVGLI_VZVO

278-297

PVGLB_HSV2H

79-99

PVGL2_CVM4

1317-1338

PVGLM_BUNGE

117-136

PVGLB_HSV2S

65-85

PVGL2_CVMA5

1265-1286

PVGLM_PHV

152-171

PVGLB_HBV6U

72-92

PVGL2_CVMJH

1176-1197

PVGLM_PTPV

997-1016

PVGLB_HSVB2

279-299

PVGLB_HSV11

83-104

PVGLM_PUUMH

155-174

PVGLB_HSVSA

63-83

PVGLB_HSV1F

82-103

PVGLM_PUUMS

155-174

PVGLB_MCMVS

738-758

PVGLB_HSV1K

82-103

PVGLM_RVFV

830-849

PVGLF_PI3H4

283-303

PVGLB_HBV1P

83-104

PVGLM_RVFVZ

830-849

PVGLG_RABVE

454-474

PVGLB_MCMVS

135-156

PVGLM_UUK

655-674

PVGLG_RABVH

454-474

PVGLC_PRVIF

446-467

PVGLY_LYCVW

89-108

PVGLG_RABVP

454-474

PVGLF_CDVO

336-357

PVGNB_CPMV

1165-1184

PVGLG_RABVS

454-474

PVGLF_MEASE

224-245

PVM3_REOVD

521-540

PVGLG_RABVT

454-474

PVGLF_MEASI

227-248

PVME1_CVBM

171-190

PVGLH_MCMVS

670-690

PVGLF_MEASY

224-245

PVME1_CVH22

136-155

PVGLM_BUNL7

1325-1345

PVGLF_MUMPM

446-467

PVME1_CVPFS

174-193

PVGLM_BUNSH

1325-1345

PVGLF_MUMPR

446-467

PVME1_CVPPU

174-193

PVGLM_BUNYW

996-1016

PVGLF_MUMPS

446-467

PVME1_CVPRM

174-193

PVGLM_HANTB

999-1019

PVGLF_PHODV

305-326

PVME1_CVTKE

171-190

PVGLM_HANTH

1000-1020

PVGLF_PI1HC

456-477

PVGLM_HANTL

1001-1021

PVGLF_PI2H

450-471

PVGLM_HANTV

1001-1021

PVGLF_PI2HG

450-471

PVGLM_RVFVZ

1156-1176

PVGLF_PI2HT

450-471

PVGLM_SEOUR

1000-1020

PVGLF_PI3B

405-426

453-474

PVGLM_SEOUS

999-1019

PVGLF_PI3H4

453-474

PVGLM_UUK

925-945

PVGLF_RINDK

220-241

PVGLY_LYCVA

12-32

PVGLF_RINDL

220-241

PVGLY_LYCVW

12-32

PVGLF_SEND5

460-481

PVGLY_PIARV

12-32

PVGLF_SENDF

460-481

PVGNB_CPMV

141-161

PVGLF_SENDH

460-481

PVMAT_MUMPS

310-330

PVGLF_SENDJ

460-481

PVMAT_NDVA

309-329

PVGLF_SENDZ

460-481

PVMAT_NDVB

309-329

PVGLF_SV41

453-474

PVMAT_PI2HT

308-328

PVGLF_SV5

446-467

PVMAT_PI4HA

312-332

PVGLH_HCMVA

691-712

PVMAT_PI4HB

312-332

PVGLH_HCMVT

690-711

PVMAT_SV41

308-328

PVGLH_HSVE4

304-325

PVMAT_SV5

308-328

PVGLH_HSVEB

297-318

PVME1_IBV6

74-94

PVGLH_HSVSA

658-679

PVME1_IBVB

74-94

PVGL1_HSV2

2-23

PVME1_IBVB2

74-94

PVGL1_HSV23

2-23

PVME1_IBVK

74-94

PVGLM_BUNGE

197-218

PVMSA_HPBDB

201-221

PVGLM_BUNL7

190-211

PVMSA_HPBGS

209-229

PVGLM_BUNSH

190-211

PVMSA_HPBHE

293-313

PVGLM_BUNYW

193-214

PVMSA_WHV1

207-227

PVGLY_LASSG

237-258

PVMSA_WHV59

212-232

PVGLY_LASSJ

238-259

PVMSA_WHV7

212-232

PVGP8_EBV

67-88

PVMSA_WHV8

212-232

PVM01_VACCC

261-302

PVMSA_WHVBI

212-232

PVM01_VACCV

230-251

PVMSA_WHVW6

63-83

PVMAT_HRSVA

139-160

PVMAT_RINDK

200-221

239-260

PVMAT_TRTV

122-143

PVME1_CVHOC

64-85

PVMSA_HPBDB

201-222

PVMSA_HPBVO

70-91

PVMSA_HPBV2

244-265

PVMSA_HPBV4

244-265

PVMSA_HPBV9

244-265

PVMSA_HPBVA

233-254

PVMSA_HPBVD

70-91

PVMSA_HPBVI

233-254

PVMSA_HPBVJ

233-254

PVMSA_HPBVL

233-254

PVMSA_HPBVN

70-91

PVMSA_HPBVO

233-254

PVMSA_HPBVP

244-265

PVMSA_HPBVR

244-265

PVMSA_HPBVS

70-91

PVMSA_HPBVW

233-254

PVMSA_HPBVY

223-254

PVMSA_HPBVZ

233-254

PVMT2_IAANN

25-46

PVMT2_IABAN

25-46

PVMT2_IAFOW

25-46

PVMT2_IAFPR

25-46

PVMT2_IAFPW

25-46

PVMT2_IALE1

25-46

PVMT2_IALE2

25-46

PVMT2_IAMAN

25-46

PVMT2_IAPUE

25-46

PVMT2_IASIN

25-46

PVMT2_IAUDO

25-46

PVMT2_IAWIL

25-46

TABLE VIII

Search Results Summary for P7CTLZIP,

P8CTLZIP, and P9CTLZIP Motifs

P7CTLZIP

P8CTLZIP

P9CTLZIP

LIBRARY FILE

LIBRARY FILE

LIBRARY FILE

PEN_BAEVM

202-224

PENV1_FRSFV

380-403

PENV_BLVAF

303-327

PENV_HV1B1

498-520

PNEV2_FRSFV

380-403

PENV_BLVAU

303-327

PENV_HV1B8

493-516

PENV_BIV06

178-201

PENV_BLVAV

303-327

PENV_HV1BN

494-516

PENv_BIV27

207-230

PENV_BLVB2

303-327

PENV_HV1BR

503-526

PENV_FOAMV

664-887

PENV_BLVB6

303-327

PENV_HV1EL

495-517

PENV_HV1Z3

175-198

PENV_BLVJ

303-327

PENV_HV1H2

498-520

PENV_HV2BE

3-26

781-804

PENV_FIVPE

781-806

PENV_HV1H3

498-520

PENV_HV2CA

750-773

PENV_FIVSD

779-803

PENV_HV1J3

510-532

PENV_HV2D1

3-26

772-795

PENV_FIVT2

780-804

PENV_HV1JR

490-512

PENV_HV2G1

772-795

PHEMA_CVBLY

391-415

PENV_HV1KB

504-529

PENV_HV2NZ

777-800

PHEMA_CVBM

391-415

PENV_HV1MA

500-522

PENV_JSRV

541-564

PHEMA_CVBQ

391-415

PENV_HV1MF

496-518

PENV_SFV1

884-887

PHEMA_CHVOC

391-415

PENV_HV1ND

488-510

PENV_SFV3L

861-804

PHEMA_INCCA

442-446

PENV_HV1PV

496-520

PENV_SIVM1

803-826

PHEMA_INCEN

430-454

PENV_HV1S1

489-511

PENV_SIVMK

802-825

PHEMA_INCGL

430-454

PENV_HV1Z2

123-145

495-517

PENV_SIVML

801-824

PHEMA_INCHY

429-453

PENV_HV1Z6

497-519

PENV_SIVS4

806-829

PHEMA_INCJH

443-467

PENV_HV1Z8

505-527

PENV_SIVSP

810-833

PHEMA_INCKY

429-453

PENV_HV1ZH

498-520

PHEMA_CDVO

200-223

PHEMA_INCMI

429-453

PENV_JSRV

376-398

PHEMA_PI2H

65-88

PHEMA_INCNA

429-453

PENV_MPMV

213-235

PHEMA_PI2HT

65-88

PHEMA_INCP1

430-454

PENV_SRV1

213-235

PVF11_VACCC

161-184

PHEMA_INCP2

430-454

PHEMA_IAAIC

37-59

PVF15_VACCC

25-48

PHEMA_INCP3

430-454

PHEMA_IABAN

21-43

PVF15_VACCP

3-26

PHEMA_INCTA

430-454

PHEMA_IADA3

37-59

PVG1L_AMEPV

313-336

PHEMA_INCYA

430-454

PHEMA_IADH2

21-43

PVG28_HSVI1

491-514

PHEMA_MUMPM

101-125

PHEMA_IADH3

21-43

PVG43_HSVI1

322-345

PHEMA_MUMPR

101-125

PHEMA_IADH4

21-43

PVG52_HSVI1

229-252

PHEMA_MUMPS

101-125

PHEMA_IADH5

21-43

PVG67_HSVI1

722-745

PHEMA_PI1HW

29-53

PHEMA_IADH6

21-43

PVGL2_CVBF

10-33

PVENV_BEV

62-88

PHEMA_IADH7

21-43

PVGL2_CVBL9

651-674

PVF05_BACCC

280-304

PHEMA_IADM2

37-59

PVGL2_CVBLY

10-33

PVF05_VACCP

380-304

PHEMA_IADMA

28-50

PVGL2_CVM4

1267-1280

PVF05_VACCV

281-305

PHEMA_IADU3

37-59

PVGL2_CVMA5

1215-1238

PVF09_VACCC

176-200

PHEMA_IAEN6

21-43

PVGL2_CVMJH

1126-1149

PVF09_VACCV

176-200

PHEMA_IAEN7

37-59

PVGL2_CVPFS

1274-1297

PVGO1_VZVD

58-82

PHEMA_IAMAO

37-59

PVGL2_CVPPU

1272-1295

PVG10_HSVSA

355-379

PHEMA_IAME1

37-59

PVGL2_CVPR8

1050-1073

PVG12_HSVSA

68-92

PHEMA_IAME2

37-59

PVGL2_CVPRM

1050-1073

PVG19_HSVI1

88-112

PHEMA_IAME6

21-43

PVGL2_FIPV

1277-1300

PVG28_HSVI1

173-197

PHEMA_IANT6

37-59

PVGL2_IBV6

196-219

PVG43_HSVI1

109-133

PHEMA_IAQU7

21-43

PVGL2_IBVB

95-218

PVG87_HSVI1

108-132

1005-1029

PHEMA_IATKM

33-55

PVGL2_IBVD2

196-219

PVG72_HSVI1

720-744

PHEMA_IAUDO

37-59

PVGL2_IBVD3

196-219

PVGF1_IBVB

3601-3826

PHEMA_IAVI7

38-60

PVGL2_IBVK

195-218

PVGL8_HSVMD

589-613

PHEMA_IAX31

37-59

PVGL2_IBVM

195-218

PVGLB_ILTV8

597-621

PHEMA_IAZCO

37-59

PVGL2_IBVU1

178-201

PVGLB_ILTV3

607-631

PHEMA_IAZH2

21-43

PVGL2_IBVU2

178-201

PVGLB_ILTVT

607-631

PHEMA_IAZH3

21-43

PVGL2_IBVU3

178-201

PVGLE_HSVI1

413-437

PHEMA_IAZUK

37-59

PVGLB_HCMVA

525-558

PVGLE_VZVD

489-493

PHEMA_PHODV

36-58

PVGLB_HCMVT

536-559

PVGLF_SVS

401-425

PHEMA_PI2H

65-87

PVGLS_HSVSA

483-506

PVGLH_HCMVA

574-599

PHEMA_PI2HT

65-87

PVGLB_MCMV8

566-589

PVGLH_HCMVT

573-597

PVFP7_CAFVK

89-111

PVGLC_HSVI1

467-490

PVGLH_HSV11

443-467

803-827

PVFUS_VACC6

72-94

PVGLC_HSV1K

467-490

PVGLH_HSV1E

443-467

803-827

PVGO1_HSVI1

317-339

PVGLC_HSV2

435-458

PVGLM_BUNL7

31-55

PVGO3_VACCC

50-72

PVGLC_HSV23

436-459

PVGLM_BUNSH

31-55

PVGO3_VARV

50-72

PVGLM_BUNL7

1387-1410

PVGLM_HANTH

694-718

PVGO4_VACCC

11-33

PVGLM_BUNSH

1387-1410

PVGLM_RVFV

344-368

PVGO4_VARV

11-33

PVGLM_UUK

966-989

PVGLM_RVFVZ

344-368

PVG19_HSVI1

88-110

PVGLY_JUNIN

12-35

PVGLM_UUK

561-585

PVG28_HSVI1

173-195

PVGLY_LASSG

12-35

PVGNM_CPMV

311-335

PVG29_HSVI1

20-42

PVGLY_LASSJ

12-35

PVGP2_EBV

657-681

PVG46_HSVI1

134-156

PVGLY_LYCVA

12-35

PVGP3_EBV

854-878

PVG48_HSVSA

71-93

PVGLY_LYCVW

12-35

PVM1_REOVD

380-304

PVG58_HSVSA

266-288

PVGLY_MOPEI

12-35

PVM1_REOVL

280-304

PVG59_HSVI1

267-289

PVGLY_TACV

12-35

PVM21_REOVD

188-192

PVG5_SPV4

42-64

PVGLY_TACV5

12-35

PVM22_REOVD

168-192

PVG60_HSVI1

53-75

PVGLY_TACV7

12-35

PVM2_REOVJ

168-192

PVG85_HSVI1

1347-1369

PVGLY_TACVT

12-35

PVM2_REOVL

168-192

PVG6_SPV1R

60-82

PVGNM_CPMV

741-764

PVMAT_MEAS1

87-111

PVGL2_IBV6

1055-1078

PVM1_REOVD

324-347

454-477

PVMAT_SSPVB

314-338

PVGL2_IBVB

1055-1077

PVM1_REOVL

454-477

PVME1_CVBM

137-161

PVGL2_IBVD2

1056-1078

PVMAT_MUMPS

227-250

PVME1_CVHOC

137-161

PVGL2_IBVK

1055-1077

PVMSA_HPBDB

269-292

PVME1_CVTKE

137-161

PVGL2_IBVM

1055-1077

PVMSA_HPBDC

268-291

PVME1_IBV6

74-98

PVGLB_HSV6U

117-139

PVMSA_HPBDU

231-254

PVME1_IBVB

74-98

PVGLV_HSVB2

745-767

PVSMA_HPBDW

269-292

PVME1_IBVB2

74-98

PVGLC_HSVMB

399-421

PVMSA_HPBHE

236-259

PVME1_IBVK

74-98

PVGLC_HSVMG

398-420

PVMSA_HPBG8

271-295

PVGLC_HSVMM

399-421

PVMSA_WHV1

269-293

PVGLF_BRSVA

265-287

482-504

PVMSA_WHV59

274-298

PVGLF_BRSVC

484-506

PVMSA_WHV7

274-298

PVGLF_BRSVR

484-506

PVMSA_WHV8

274-298

PVGLF_HRSV1

484-506

PVMSA_WHV8I

274-298

PVGLF_HRSVA

484-506

PVMSA_WHVW6

125-149

PVGLF_HRSVL

484-506

PVGLF_HRSVR

484-506

PVGLF_TRTV

452-474

PVGLG_IHNV

77-99

PVGLG_VHSV0

406-428

PVGLH_H3VE4

814-836

PVGLH_HSVEB

807-829

PVGLI_HCMVA

158P14 180

PVGLM_PTPV

743-765

PVGLP_BEV

430-452

1546-1568

PVGLY_LASSG

428-448

PVGLY_LASSJ

427-449

PVGLY_MOPEI

425-447

PVGP2_EBV

657-679

PVGP3_EBV

854-878

PVM1_REOVD

414-436

PVM1_REOVL

414-438

PVM3_REOVD

304-326

PVMAT_PI1HC

195-217

PVMAT_PI2HT

132-164

PVMAT_SENDF

195-217

PVMAT_SENDH

195-217

PVMAT_SENDZ

195-217

PVMAT_SV41

132-154

PVMEM_EBV

131-153

PVMP_CERV

293-315

TABLE IX

Search Results Summary for P12CTLZIP Motif

P12LZIPC

LIBRARY FILE

PENV1_FRSFV

380-407

PENV2_FRSPV

380-407

PENV_AVISU

98-117

PENV_BAEVM

202-224

PENV_BIVO6

525-546

PENV_BIV27

147-168

207-230

463-479

554-575

PENV_BLVAF

303-327

PENV_BLVAU

303-327

PENV_BLVAV

303-327

PENV_BLVB2

303-327

PENV_BLVB6

303-327

PENV_BLVJ

303-327

PENV_FENV1

30-47

225-246

630-651

PENV_FLVC6

38-55

624-645

PENV_FLVGL

9-29

447-468

606-626

PENV_FLVLB

467-488

613-646

PENV_FLVSA

444-465

602-623

PENV_FOAMV

153-174

255-275

300-325

481-496

710-727

864-887

924-951

957-978

PENV_FSVGA

9-29

467-488

625-646

PENV_FSVGB

447-468

605-626

PENV_FSVSM

450-471

608-629

PENV_FSVST

467-488

PENV_GALV

52-73

519-540

PENV_HV181

498-520

PENV_HV188

493-515

PENV_HV18N

494-516

PENV_HV18R

503-525

FENV_HV1C4

428-448

PENV_HV1EL

495-517

PENV_HV1H2

498-520

PENV_HV1H3

498-520

PENV_HV1J3

510-532

PENV_HV1JR

490-512

PENV_HV1KB

604-626

552-579

752-768

PENV_HV1MA

438-453

500-522

PENV_HV1MF

496-518

PENV_HV1ND

488-510

PENV_HV1OY

123-140

PENV_HV1PV

498-520

PENV_HV1RH

445-460

PENV_HV1S1

489-511

7380-754

PENV_HV1Z2

123-145

410-427

495-517

PENV_HV1Z3

117-133

175-198

PENV_WV1Z6

497-519

PENV_HV1Z8

505-527

PENV_HV1ZH

123-142

438-453

498-520

PENV_HV2BE

3-26

750-775

781-804

PENV_HV2CA

750-777

PENV_HV2D1

3-26

741-766

772-795

PENV_HV2D2

9-28

PENV_HV2G1

741-766

772-795

PENV_HV2NZ

742-767

777-800

PENV_HV2RO

751-776

PENV_HV2SB

743-768

778-804

PENV_HV2ST

745-770

PENV_JSRV

104-119

299-325

376-398

541-564

PENV_MCFF

600-621

PENV_MCFF3

601-622

PENV_MLVAV

630-651

PENV_MLVCB

625-646

PENV_MLVF5

639-660

PENV_MLVFF

639-660

PENV_MLVFP

639-660

PENV_MLVHO

626-647

PENV_MLVKI

187-188

PENV_MLVMO

629-650

PENV_MLVRD

624-645

PENV_MLVRK

624-645

PENV_MMTVB

643-663

PENV_MMTVG

643-663

PENV_MPMV

213-235

PENV_MSVFB

170-191

PENV_OMVVS

75-100

658-683

PENV_RMCFV

603-624

PENV_RSVP

42-69

533-552

PENV_SFV1

300-325

710-727

864-887

924-951

957-978

PENV_SFV3L

157-178

304-329

707-724

861-884

921-948

954-975

PENV_SIVA1

437-458

PENV_SIVAG

442-463

PENV_SIVAI

421-442

PENV_SIVAT

435-456

PENV_SIVGB

93-109

PENV_SIVM1

766-793

803-826

PENV_SIVM2

139-154

765-792

802-825

PENV_SIVMK

139-154

764-791

801-824

PENV_SIVML

769-789

806-829

PENV_SIVS4

773-793

810-833

PENV_SMSAV

42-63

PENV_SRV1

213-235

PHEMA_CDVO

36-53

200-223

PHEMA_CVBLY

391-415

PHEMA_CVBM

391-415

PHEMA_CVBQ

391-415

PHEMA_CYNOC

391-415

PHEMA_CVMA5

402-123

PHEMA_CVMS

403-418

PHEMA_IAAIC

37-59

322-339

PHEMA_IABAN

21-43

306-323

PHEMA_IABUD

320-337

PHEMA_IACKA

320-337

PHEMA_IACKG

81-101

316-333

PHEMA_IACKP

302-319

PHEMA_IACKQ

302-319

PHEMA_IACKS

319-336

PHEMA_IACKV

230-246

315-332

PHEMA_IADA1

320-337

PHEMA_IADA2

319-336

PHEMA_IADA3

37-59

322-339

PHEMA_IADCZ

320-337

PHEMA_IADE1

266-287

PHEMA_IADH1

306-323

PHEMA_IADH2

21-43

306-323

PHEMA_IADH3

21-43

306-323

PHEMA_IADH4

21-43

306-323

PHEMA_IADH5

21-43

PHEMA_IADH6

21-43

306-323

PHEMA_IADH7

21-43

306-323

PHEMA_IADM2

37-59

322-339

PHEMA_IADMA

26-50

81-101

PHEMA_IADNZ

320-337

PHEMA_IADU3

37-59

322-339

PHEMA_IAEN6

21-43

306-323

PHEMA_IAEN7

37-59

322-339

PHEMA_IAFPR

230-246

315-332

PHEMA_IAGRE

320-337

PHEMA_IAGU2

320-337

PHEMA_IAGUA

319-336

PHEMA_IAHAL

321-338

PHEMA_IAHAR

230-246

315-332

PHEMA_IAHC6

230-246

315-332

PHEMA_IAHC7

230-246

315-332

PHEMA_IAHCD

230-246

315-332

PHEMA_IAHDE

230-246

315-332

PHEMA_IAHFO

236-252

321-338

PHEMA_IAHK6

321-338

PHEMA_IAHK7

236-252

321-338

PHEMA_IAHLE

230-246

315-332

PHEMA_IAHLO

230-246

315-332

PHEMA_IAHMI

236-252

321-338

PHEMA_IAHNM

236-252

321-338

PHEMA_IAHNN

315-332

PHEMA_IAHPR

315-332

PHEMA_IAHRO

236-252

321-338

PHEMA_IAHSA

236-252

321-338

PHEMA_IAHSP

230-246

315-332

PHEMA_IAHSW

230-246

315-332

PHEMA_IAHTE

236-252

321-338

PHEMA_IAHTO

236-252

321-338

PHEMA_IAHUR

236-252

321-338

PHEMA_IAJAP

317-334

PHEMA_IAMAA

197-223

319-336

PHEMA_IAMAB

202-228

324-341

PHEMA_IAMAO

37-59

322-339

PHEMA_IAME1

37-59

322-339

PHEMA_IAME2

37-59

322-339

PHEMA_IAME6

21-43

PHEMA_IAMIN

85-101

231-247

316-333

PHEMA_IANT6

37-59

322-339

PHEMA_IAPIL

320-337

PHEMA_IAQU7

21-43

306-323

PHEMA_IARUD

320-337

PHEMA_IASE2

320-337

PHEMA_IASH2

321-338

PHEMA_IASTA

230-246

315-332

PHEMA_IATAI

33-55

320-337

PHEMA_IATKI

233-249

PHEMA_IATKR

230-246

PHEMA_IATKW

229-245

PHEMA_IAUDO

37-59

322-339

380-397

PHEMA_IAVI7

38-60

323-340

PHEMA_IAX31

37-59

PHEMA_IAZCO

37-59

322-339

PHEMA_IAZH2

21-43

306-323

PHEMA_IAZH3

21-43

306-323

PHEMA_IAZUK

37-59

322-339

PHEMA_INBAA

115-131

295-310

PHEMA_INBBE

123-139

303-318

PHEMA_INBBO

116-132

293-308

PHEMA_INBEN

123-139

301-316

PHEMA_INBFU

108-124

266-301

PHEMA_INBGL

119-135

296-311

PHEMA_INBHK

116-132

293-308

PHEMA_INBIB

108-124

288-303

PHEMA_INBID

120-136

299-314

PHEMA_INBLE

123-139

302-317

PHEMA_INBMD

113-129

292-307

PHEMA_INBME

116-132

296-311

PHEMA_INBNA

108-124

288-303

PHEMA_INBOR

123-139

301-316

PHEMA_INBSI

123-139

301-316

PHEMA_INBSJ

119-135

298-313

PHEMA_INBUS

116-132

294-309

PHEMA_INBVI

116-132

296-311

PHEMA_INBVK

123-139

303-318

PHEMA_INBYB

108-124

288-301

PHEMA_INCCA

442-466

PHEMA_INCEN

430-454

PHEMA_INCGL

430-454

PHEMA_INCHY

429-453

PHEMA_INCJH

443-467

PHEMA_INCKY

429-153

PHEMA_INCMI

429-153

PHEMA_INCNA

429-453

PHEMA_INCP1

430-454

PHEMA_INCP2

430-454

PHEMA_INCP3

430-454

PHEMA_INCTA

430-454

PHEMA_INCYA

430-454

PHEMA_MUMPM

133-148

225-246

387-394

397-417

PHEMA_MUMPR

101-125

133-148

225-246

397-417

PHEMA_MUMPS

101-125

133-148

225-246

367-394

397-417

PHEMA_NDVA

93-110

PHEMA_NDVB

93-110

PHEMA_NDVD

93-110

PHEMA_NDVH

93-110

PHEMA_NDVI

93-110

PHEMA_NDVM

93-110

PHEMA_NDVQ

93-110

PHEMA_NDVTG

93-110

PHEMA_NDVU

93-110

PHEMA_PHODV

36-56

213-234

493-513

PHEMA_PI1HW

29-53

322-342

345-360

486-503

PHEMA_PI2H

13-40

65-88

118-136

PHEMA_PI2HT

13-40

65-88

118-136

PHEMA_PI3B

111-128

272-299

324-340

PHEMA_PI3H4

111-128

272-299

324-340

PHEMA_PI3HA

111-128

272-299

324-340

PHEMA_PI3HT

111-128

272-299

324-340

PHEMA_PI3HU

111-128

272-299

324-340

PHEMA_PI3HV

111-128

272-299

324-340

PHEMA_PI3HW

111-128

272-299

324-340

PHEMA_PI3HX

111-128

272-299

324-340

PHEMA_PI4HA

50-67

PHEMA_RINDK

368-383

PHEMA_RINDL

4-30

PHEMA_SEND5

322-342

PHEMA_SENDF

322-342

PHEMA_SENDH

322-342

PHEMA_SENDJ

322-342

PHEMA_SENDZ

322-342

PHEMA_SV41

55-73

85-102

107-132

PHEMA_SV5

7-28

84-101

379-400

PHEMA_SV5CM

7-28

84-101

379-400

PHEMA_SV5CP

7-28

84-101

379-400

PHEMA_SV5LN

7-28

84-101

379-400

PHEMA_VACCC

173-192

PHEMA_VACCI

173-192

PHEMA_VACCT

173-192

PHEMA_VACCV

173-192

PVENV_BEV

62-86

87-114

PVENV_DNVI1

42-57

484-511

PVENV_EAV

25-41

PVENV_LELV

27-47

148-168

PVENV_MCV1

61-80

PVENV_MCV2

61-80

306-333

PVENV_THOGV

196-221

356-383

473-491

PVFO5_VACCC

280-305

PVFO5_VACCP

280-305

PVFO5_VACCV

280-305

PVFO9_VACCC

176-200

PVFO9_VACCV

176-200

PVF11_VACCC

161-184

PVF15_VACCC

25-48

PVF15_VACCP

3-26

PVFP1_FOWPV

297-323

PVFP2_FOWPV

68-104

PVFP7_CAPVK

89-111

PVFP7_FOWPV

65-90

PVFP8_CAPVK

51-76

PVFUS_ORFNZ

29-48

PVFUS_VACC6

72-94

PVGO1_HSVEB

169-195

PVGO1_HSVI1

210-225

317-339

589-616

PVGO1_VACCC

298-318

376-395

PVGO1_VACCV

237-257

315-334

PVGO1_VARV

298-318

376-395

PVGO1_VZVD

58-82

PVGO3_VACCC

50-72

PVGO3_VARV

50-72

PVGO4_VACCC

11-33

PVGO4_VARV

11-33

PVGO6_VACCC

31-51

PVGO6_VARV

31-51

PVGO8_HSVI1

134-149

159-185

PVG10_HSVI1

35-54

PVG10_HSVSA

109-124

355-379

PVG11_HSVI1

103-122

150-176

PVG12_HSVI1

151-178

270-286

PVG12_HSVSA

68-92

PVG15_HSVEB

194-209

PVG19_HSVI1

88-112

PVG1L_AMEPV

313-336

PVG1_SPV1R

76-92

359-676

PVG22_HSVI1

300-327

PVG23_HSVI1

314-335

PVG27_HSVI1

158-184

PVG27_HSVSA

209-226

PVG28_HSVI1

173-197

491-518

PVG28_HSVSA

14-40

PVG29_HSVI1

20-42

PVG30_HSVI1

166-191

PVG32_VZVD

90-109

PVG36_HSVSA

108-123

344-362

PVG37_HSVI1

284-299

PVG39_HSVI1

646-675

970-990

1038-1065

PVG40_HSVI1

14-32

PVG41_HSVI1

11-38

62-81

244-260

PVG43_HSVI1

109-133

157-178

322-345

521-538

PVG46_HSVI1

134-156

580-607

937-963

1244-1270

PVG48_HSVSA

71-93

PVG50_HSVI1

5-30

58-83

PVG50_HSVSA

63-81

95-117

206-233

PVG51_HSVI1

29-49

84-102

PVG52_HSVI1

229-252

PVG55_HSVI1

22-37

143-168

288-309

PVG55_HSVSA

85-106

PVG56_HSVI1

1155-1176

PVG58_HSVSA

130-146

266-288

293-319

330-346

PVG59_HSVI1

142-161

267-289

PVG5_SPV4

42-84

PVG60_HSVI1

30-51

53-75

PVG61_HSVI1

76-102

117-136

PVG63_HSVI1

238-259

336-383

PVG64_HSVI1

420-445

PVG65_HSVI1

117-137

155-173

362-378

518-533

1147-1174

1347-1369

PVG67_HSVI1

108-132

171-188

318-344

722-745

1005-1029

1072-1091

1315-1341

PVG6_SPV1R

60-82

PVG70_HSVI1

184-209

PVG71_HSVSA

69-105

PVG72_HSVI1

445-471

535-561

720-744

1252-1269

PVG74_HSVSA

124-151

PVG9_SPV1R

57-72

PVGF1_IBVB

1587-1606

1856-1877

2108-2127

2210-2226

2788-2806

2973-2999

3073-3090

3374-3390

3601-

3625

PVGH3_HCMVA

157-178

PVGL2_CVBF

10-33

123-139

174-190

264-279

991-1017

1259-1280

PVGL2_CVBL9

123-139

174-190

264-279

651-674

991-1017

1259-1280

PVGL2_CVBLY

10-33

123-139

174-190

264-279

991-1017

1259-1280

PVGL2_CVBM

123-139

174-190

264-279

991-1017

1259-1280

PVGL2_CVBQ

31-47

123-139

174-190

991-1017

1259-1280

PVGL2_CVBV

123-139

174-190

264-279

991-1017

1259-1280

PVGL2_CVH22

768-794

1053-1071

1115-1134

PVGL2_CVM4

95-111

999-1025

1267-1290

1317-1338

PVGL2_CVMA5

95-111

947-973

1215-1238

1265-1286

PVGL2_CVMJH

95-111

858-884

1126-1149

1178-1197

PVGL2_CVPFS

64-83

442-457

800-816

1038-1064

1274-1297

PVGL2_CVPPU

64-83

440-455

504-519

798-814

1036-1082

1272-1295

PVGL2_CVPR8

218-233

576-592

814-840

1050-1073

PVGL2_CVPRM

218-233

576-592

814-840

1050-1073

PVGL2_FIPV

803-819

1041-1067

1277-1300

PVGL2_IBV6

196-219

588-607

771-797

1056-1081

1094-1111

PVGL2_IBVb

195-218

587-606

770-796

1055-1080

PVGL2_IBVD2

196-219

588-607

771-797

1056-1081

PVGL2_IBVD3

196-219

PVGL2_IBVK

195-218

587-606

770-796

1065-1080

PVGL2_IBVM

195-218

378-398

587-606

770-795

1065-1080

PVGL2_IBVU1

178-201

PVGL2_IBVU2

178-201

PVGL2_IBVU3

178-201

PVGLB_EBV

732-752

PVGLB_HCMVA

535-558

706-732

750-777

PVGLB_HCMVT

536-559

707-733

751-778

PVGLB_HSV11

83-104

PVGLB_HSV1F

82-103

PVGLB_HSV1K

82-103

PVGLB_HSV1P

83-104

PVGLB_HSV23

79-99

PVGLB_HSV2H

79-99

PVGLB_HSV28

65-85

PVGLB_HSV6U

72-92

117-144

PVGLB_HSVB1

560-578

689-707

PVGLB_HSVB2

279-299

745-767

PVGLB_JSVBC

692-710

PVGLB_HSVE1

738-753

PVGLB_HSVE4

675-692

PVGLB_HSVEA

736-753

PVGLB_HSVEB

736-753

PVGLB_HSVEL

736-753

PVGLB_HSVMD

589-613

PVGLB_HSVSA

483-506

584-602

701-716

PVGLB_ILTV6

256-275

597-621

740-758

PVGLB_ILTVS

266-285

607-631

750-768

PVGLB_ILTVT

266-285

607-631

750-768

PVGLB_MCMVS

135-156

566-589

738-765

PVGLB_PRVIF

203-218

PVGLB_VXVD

522-538

PVGLC_HSV11

467-493

PVGLC_HSV1K

3-22

467-493

PVGLC_HSV2

435-458

PVGLC_HSV23

436-459

PVGLC_HSVBC

475-494

PVGLC_HSVE4

444-459

PVGLC_HSVEB

427-442

PVGLC_HSVMB

399-421

PVGLC_HSVMG

398-420

PVGLC_HSVMM

399-421

PVGLC_PRVIF

180-197

446-472

PVGLC_VZVD

431-449

PVGLC_VZVS

431-449

PVGLD_HSV11

79-94

PVGLD_HSV2

79-94

PVGLE_HSV11

104-129

413-437

PVGLE_VZVD

469-493

PVGLF_BRSVA

205-221

265-287

482-504

PVGLF_BRSVC

205-221

265-287

484-506

PVGLF_BRSVR

205-221

265-287

484-508

PVGLF_CDVO

336-361

398-414

583-589

PVGLF_HRSV1

205-221

265-287

484-506

PVGLF_HRSVA

205-221

265-287

484-506

PVGLF_HRSVL

205-221

265-287

484-506

PVGLF_HRSVR

205-221

265-287

484-506

PVGLF_MEASE

224-245

286-302

451-477

PVGLF_MEASI

277-248

289-305

454-480

PVGLF_MEASY

224-245

286-302

451-477

PVGLF_MUMPM

276-292

446-467

PVGLF_MUMPR

276-292

446-467

PVGLF_MUMPS

5-20

276-292

446-467

PVGLF_NDVA

273-289

PVGLF_NDVB

273-289

PVGLF_NDVM

273-289

PVGLF_NDVT

273-289

PVGLF_NDVTG

273-289

PVGLF_NDVU

273-289

PVGLF_PHODV

269-285

305-326

367-383

531-558

PVGLF_PI1HC

456-477

PVGLF_PI2H

450-471

PVGLF_PI2HG

450-471

PVGLF_PI2HT

450-471

PVGLF_PI3B

283-310

405-426

453-474

PVGLF_PI3H4

2-20

283-310

453-474

PVGLF_RINDK

220-241

282-298

447-473

PVGLF_RINDL

220-241

282-298

447-473

PVGLF_SEND5

460-481

PVGLF_SENDF

460-481

PVGLF_SENDH

460-481

PVGLF_SENDJ

460-481

PVGLF_SENDZ

460-481

PVGLF_SV41

453-474

PVGLF_SV5

401-425

446-467

PVGLF_TRTV

175-191

452-474

PVGLG_IHNV

77-99

PVGLG_RABVE

454-474

PVGLG_RABVH

372-391

454-474

PVGLG_RABVP

454-474

PVGLG_RABVS

454-474

PVGLG_RABVT

454-474

PVGLG_VHSV0

406-428

PVGLH_HCMVA

211-237

365-382

574-598

691-712

PVGLH_HCMVT

210-236

364-381

573-597

690-711

PVGLH_HSV11

245-262

443-467

803-827

PVGLH_HSV1E

245-262

443-467

803-827

PVGLH_HSV6G

314-332

PVGLH_HSVE4

304-325

814-836

PVGLH_HSVEB

297-318

807-832

PVGLH_HSVSA

454-479

656-679

PVGLH_MCMVS

670-890

PVGLI_HCMVA

168-160

PVGLI_HSV11

43-60

PVGLI_HSVEB

44-63

PVGLI_VZVD

278-297

PVGLM_BUNGE

117-136

197-222

PVGLM_BUNL7

31-55

81-98

190-211

1325-1345

1387-1410

PVGLM_BUNSH

31-55

81-98

190-211

1325-1345

1387-1410

PVGLM_BUNYW

193-216

1379-1404

PVGLM_HANTB

355-371

692-717

900-915

999-1019

PVGLM_HANTH

499-515

694-718

1000-1020

PVGLM_HANTL

499-515

694-718

1001-1021

PVGLM_HANTV

499-515

694-718

1001-1021

PVGLM_PHV

152-171

PVGLM_PTPV

743-765

997-1016

1275-1302

PVGLM_PUUMH

155-174

509-525

712-729

PVGLM_PUUMS

155-174

509-525

712-729

1092-1117

PVGLM_RVFV

53-80

344-368

830-858

PVGLM_RVFVZ

53-80

344-366

830-858

1156-1176

PVGLM_SEOUR

355-371

693-718

901-916

1000-1020

PVGLM_SEOUS

355-371

692-717

900-915

999-1019

PVGLM_UUK

581-585

855-874

826-842

925-952

966-989

PVGLP_BEV

430-452

889-885

1099-1124

1546-1588

PVGLX_PRVRI

149-176

PVGLY_JUNIN

12-38

PVGLY_LASSG

12-38

237-258

426-448

PVGLY_LASSJ

12-38

238-259

427-449

PVGLY_LYCVA

12-38

PVGLY_LYCVW

12-38

69-108

PVGLY_MOPEI

12-38

425-447

PVGLY_PIARV

12-38

441-466

PVGLY_TACV

12-38

PVGLY_TACV5

12-38

PVGLY_TACV7

12-38

PVGLY_TACVT

12-38

PVGNB_CPMV

141-161

568-594

757-783

1110-1135

1165-1184

PVGNM_BPMV

678-696

PVGNM_CPMV

311-335

741-764

1021-1037

PVGP2_EBV

657-681

PVGP3_EBV

854-878

PVGP8_EBV

67-88

PVMO1_VACCC

134-159

177-195

281-302

PVMO1_VACCV

83-108

126-144

230-251

PVM1_REOVD

141-168

227-245

280-304

324-347

414-436

454-477

PVM1_REOVL

141-168

227-245

280-304

414-436

454-477

PVM21_REOVD

168-192

PVM22_REOVD

168-192

PVM2_REOVJ

168-192

PVM2_REOVL

168-192

PVM3_REOVD

304-326

521-540

PVMAT_BRSVA

37-62

PVMAT_CDVO

148-165

283-309

PVMAT_HRSVA

44-62

139-180

PVMAT_LPMV

311-338

PVMAT_MEASE

283-309

PVMAT_MEASH

283-309

PVMAT_MEASI

87-111

PVMAT_MEASU

283-309

PVMAT_MUMPS

191-207

227-250

310-330

PVMAT_NDVA

135-151

190-208

309-329

PVMAT_NDVB

135-151

190-208

309-329

PVMAT_PI1HC

195-217

PVMAT_PI2HT

132-154

189-205

308-328

PVMAT_PI4HA

312-332

PVMAT_PI4HB

312-332

PVMAT_RINDK

200-221

239-260

283-309

PVMAT_SENDF

195-217

PVMAT_SENDH

195-217

PVMAT_SENDZ

195-217

PVMAT_SSPVB

283-309

314-336

PVMAT_SV41

132-154

189-205

308-328

PVMAT_SV5

98-114

132-148

308-335

PVMAT_SVCV

141-167

PVMAT_TRTV

122-143

PVME1_CVBM

9-36

137-161

171-190

PVME1_CVH22

136-155

PVME1_CVHOC

9-36

64-85

137-161

PVME1_CVMA5

10-37

PVME1_CVMJH

10-37

PVME1_CVPFS

174-193

PVME1_CVPPU

174-193

PVME1_CVPRM

174-193

PVME1_CVTKE

9-36

137-161

171-190

PVME1_IBV6

74-98

PVME1_IBVB

74-101

PVME1_IBVB2

74-101

PVME1_IBVK

74-98

PVMEM_EBV

131-157

178-203

PVMP_CAMVC

118-134

147-164

183-201

PVMP_CAMVD

118-134

147-164

183-201

PVMP_CAMVE

118-134

147-164

183-201

PVMP_CAMVN

118-134

147-164

183-201

PVMP_CAMVS

118-134

147-164

183-201

PVMP_CAMVW

118-134

147-164

183-201

PVMP_CERV

293-318

PVMP_FMVD

115-131

180-198

PVMP_SOCMV

122-147

273-299

PVMSA_HPBDB

201-228

269-295

PVMSA_HPBDC

194-221

268-294

PVMSA_HPBDU

157-184

231-257

PVMSA_HPBDW

194-221

269-295

PVMSA_HPBGS

209-236

271-295

380-395

PVMSA_HPSHE

236-262

293-320

PVMSA_HPBV0

70-96

PVMSA_HPBV2

185-202

244-270

PVMSA_HPBV4

185-202

244-270

PVMSA_HPBV9

244-270

PVMSA_HPBVA

174-191

233-259

PVMSA_HPBVD

11-28

70-96

PVMSA_HPBVI

233-259

PVMSA_HPBVJ

174-191

233-259

PVMSA_HPBVL

174-191

233-259

PVMSA_HPBVN

11-28

70-96

PVMSA_HPBVO

174-191

233-259

PVMSA_HPBVP

185-202

244-270

PVMSA_HPBVR

185-202

244-270

PVMSA_HPBVS

11-28

70-96

PVMSA_HPBVW

174-191

233-259

PVMSA_HPBVY

174-191

233-259

PVMSA_HPBVZ

174-191

233-259

PVMSA_WHV1

207-234

269-293

378-393

PVMSA_WHV59

212-239

274-298

383-398

PVMSA_WHV7

212-239

274-298

383-398

PVMSA_WHV8

212-239

274-298

383-398

PVMSA_WHV8I

212-239

274-298

383-398

PVMSA_WHVW6

125-149

234-249

PVMT2_IAANN

25-46

PVMT2_IABAN

25-46

PVMT2_IAFOW

25-46

PVMT2_IAFPR

25-46

PVMT2_IAFPW

25-46

PVMT2_IALE1

25-46

PVMT2_IALE2

25-46

PVMT2_IAMAN

25-46

PVMT2_IAPUE

25-46

PVMT2_IASIN

25-46

PVMT2_IAUDO

25-46

PVMT2_IAWIL

25-46

PVMT9_MYXVL

226-241

TABLE X

Search Results Summary for P23CTLZIP Motif

P23LZIPC

LIBRARY FILE

PENV_AVISU

98-136

PENV_BAEVM

202-240

526-564

PENV_BIV06

434-472

526-553

628-659

PENV_BIV27

554-582

657-688

PENV_CAEVG

44-78

PENV_EIAV1

795-828

PENV_EIAV2

795-828

PENV_EIAV3

795-828

PENV_EIAV6

796-829

PENV_EIAV9

795-828

PENV_EIAVC

795-828

PENV_EIAVW

795-828

PENV_EIAVY

798-828

PENV_FIVPE

128-166

PENV_FIVT2

46-74

PENV_FLVGL

447-475

PENV_FLVLB

487-495

PENV_FLVBA

444-472

PENV_FOAMV

44-78

481-519

552-584

PENV_FRSFB

315-350

PENV_FSVGA

467-495

PENV_FSVGB

447-475

PENV_FSVSM

450-478

PENV_FSVST

467-495

PENV_GALV

519-554

PENV_HV1A2

729-762

PENV_HV1B1

730-763

PENV_HV1B8

725-758

PENV_HV1BN

743-781

PENV_HV1BR

735-768

PENV_HV1C4

742-776

PENV_HV1EL

254-286

727-780

PENV_HV1H2

730-763

PENV_HV1H3

730-763

PENV_HV1J3

741-774

PENV_HV1JR

722-755

PENV_HV1KB

552-586

762-790

PENV_HV1MA

268-289

733-766

PENV_HV1MF

728-761

PENV_HV1MN

392-430

731-764

PENV_HV1ND

248-279

PENV_HV10Y

729-762

PENV_HV1PV

730-763

PENV_HV1RH

739-772

PENV_HV1SC

730-763

PENV_HV1W1

730-763

PENV_HV1W2

721-754

PENV_HV1Z2

264-286

727-780

PENV_HV1Z3

260-281

PENV_HV1Z6

255-286

729-762

PENV_HV2BE

781-811

PENV_HV2D1

772-802

PENV_HV2G1

772-802

PENV_HV2NZ

777-814

PENV_HV2SB

743-775

PENV_JSRV

299-332

484-515

PENV_MMTVB

435-472

PENV_MMTVG

435-472

PENV_RSVP

533-570

PENV_SFV1

44-78

492-530

PENV_SFV3L

48-82

550-588

PENV_SIVCZ

745-776

PENV_SIVGB

247-277

353-386

PENV_SIVM1

788-800

PENV_SIVMK

765-799

PENV_SIVML

511-545

764-798

PENV_SIVS4

468-486

PENV_SIVSP

462-490

810-840

PHEMA_CDVO

200-234

PHEMA_IABUD

23-55

PHEMA_IACKA

23-56

PHEMA_IACKV

517-547

PHEMA_IADA1

23-56

PHEMA_IADCZ

23-55

PHEMA_IADH6

293-323

PHEMA_IADNZ

23-55

PHEMA_IAFPR

15-51

PHEMA_IAGRE

23-55

PHEMA_IAMAA

22-54

PHEMA_IAMAB

27-59

PHEMA_IARUD

23-55

PHEMA_IASE2

23-55

PHEMA_IASTA

517-547

PHEMA_MUMPM

19-52

101-132

PHEMA_MUMPR

19-52

101-132

PHEMA_MUMPS

19-52

101-132

PHEMA_NDVA

60-88

PHEMA_NDVB

60-88

PHEMA_NDVD

60-88

PHEMA_NDVH

60-88

PHEMA_NDVI

60-88

PHEMA_NDVM

60-88

PHEMA_NDVQ

60-88

PHEMA_NDVTG

60-88

PHEMA_NDVU

60-88

PHEMA_PI1HW

29-60

196-233

PHEMA_PI2H

13-46

334-369

PHEMA_PI2HT

13-46

334-369

PHEMA_PI3B

194-231

PHEMA_PI3H4

194-231

PHEMA_PI3HA

194-231

PHEMA_PI3HT

194-231

PHEMA_PI3HU

194-231

PHEMA_PI3HV

194-231

PHEMA_PI3HW

194-231

PHEMA_PI3HX

194-231

PHEMA_PI4HA

245-280

338-376

PHEMA_RACVI

255-293

PHEMA_RINDL

282-313

PHEMA_SEND5

16-54

196-233

PHEMA_SENDF

16-54

196-233

PHEMA_SENDH

16-54

196-233

PHEMA_SENDJ

16-54

196-233

PHEMA_SENDZ

23-54

196-233

PHEMA_SV41

55-84

330-365

PHEMA_SV5

7-36

PHEMA_SV5CM

7-41

PHEMA_SV5CP

7-41

PHEMA_SV5LN

7-35

PHEMA_VACCC

258-294

PHEMA_VACCI

259-294

PHEMA_VACCT

258-294

PHEMA_VACCV

258-294

PVENV_BEV

16-51

87-117

PVENV_DHVI1

297-335

PVENV_MCV1

203-236

PVENV_MCV2

203-236

PVENV_VACCC

208-241

PVENV_VACCI

208-241

PVENV_VACCP

208-241

PVENV_VACCV

208-241

PVF03_VACCC

2-40

61-93

PVF03_VACCV

2-40

61-93

PVFP1_FOWPV

297-330

PVFP4_FOWPV

237-267

PVFP7_CAPVK

89-118

PVFU8_VACCC

28-61

PVFU8_VACCV

28-61

PVG01_HSVI1

317-346

PVG02_HSVEB

163-196

PVG02_VACCV

92-120

PVG02_VARV

92-120

PVG03_HSVI1

108-136

PVG06_HSVI1

54-83

PVG06_VACCC

99-136

PVG06_VARV

99-136

PVG07_VACCC

113-145

PVG07_VARV

113-145

PVG09_VACCC

303-338

PVG09_VACCV

266-301

PVG09_VARV

303-338

PVG11_HSVI1

150-183

PVG12_HSV11

206-243

PVG12_HSVSA

68-106

PVG1_SPV1R

254-292

303-337

414-452

PVG22_HSVI1

300-337

647-678

PVG23_HSVI1

70-108

PVG26_HSVI1

94-125

PVG27_HSVSA

36-74

PVG28_HSVI1

491-521

PVG28_HSVSA

7-40

PVG2R_AMEPV

180-217

PVG2_SPV4

209-244

PVG35_HSVI1

15-46

190-226

PVG36_HSVSA

151-185

PVG39_HSVI1

543-577

648-682

PVG40_HSVSA

187-216

PVG41_HSVI1

11-45

202-233

PVG42_HSVI1

91-125

PVG43_HSVI1

109-140

157-185

PVG46_HSVI1

888-925

PVG48_HSVSA

329-357

PVG50_HSVSA

113-141

PVG51_HSVI1

29-64

84-120

PVG52_HSVI1

96-134

PVG55_HSVI1

100-129

PVG56_HSVI1

631-667

1091-1126

PVG58_HSVI1

342-375

480-508

PVG58_HSVSA

25-60

195-233

PVG59_HSVI1

82-118

PVG61_HSVI1

76-109

PVG64_HSVI1

55-89

363-401

420-452

PVG65_HSVI1

801-836

1190-1326

PVG67_HSVI1

150-188

1150-1185

PVG6_SPV1R

60-89

PVG71_HSVSA

128-158

PVG72_HSVI1

445-478

720-751

1158-1189

1252-1285

PVG75_HSVI1

263-291

387-422

PVG78_H8VI1

187-221

PVG7_SPV1R

18-46

PVGF1_IBVB

1719-1747

1856-1891

2108-2146

3601-3633

PVGH3_HCMVA

80-115

157-185

PVGL2_CVBF

1259-1294

PVGL2_CVBL9

651-681

1259-1294

PVGL2_CVBLY

1259-1294

PVGL2_CVBM

1259-1294

PVGL2_CVBQ

1259-1294

PVGL2_CVBV

1259-1294

PVGL2_CVH22

1053-1088

PVGL2_CVM4

1287-1304

PVGL2_CVMA5

1215-1252

PVGL2_CVMJH

1128-1163

PVGL2_CVPFS

632-665

736-764

1328-1383

PVGL2_CVPPU

630-663

734-762

1326-1381

PVGL2_CVPR8

512-540

1104-1139

PVGL2_CVPRM

408-441

1104-1139

PVGL2_FIPV

635-668

739-767

1331-1366

PVGL2_IBVB

153-188

PVGLB_HCMVA

116-147

708-743

PVGLB_HCMVT

116-147

707-744

PVGLB_HSVGU

72-110

PVGLB_HSVB1

254-288

PVGLB_HSVB2

264-299

745-774

PVGLB_HSVBC

253-287

PVGLB_ILTV6

442-472

PVGLB_ILTV8

452-482

PVGLB_IVTVT

452-482

PVGLB_MCMV8

135-163

738-776

PVGLC_HSV11

487-500

PVGLC_HSV1K

487-500

PVGLC_HSV2

435-465

PVGLC_HSV23

436-466

PVGLC_HSVBC

475-507

PVGLC_VZVD

351-388

513-548

PVGLC_VZVS

351-388

513-548

PVGLD_HSVEA

340-370

PVGLD_HSVEB

41-70

390-420

PVGLD_HSVEK

41-70

390-420

PVGLE_HSVE4

95-125

PVGLE_HSVEB

63-100

390-420

PVGLE_HSVEL

63-100

392-422

PVGLE_PRVRI

332-369

PVGLF_BRSVA

265-301

482-511

PVGLF_BRSVC

484-513

PVGLF_BRSVR

484-513

PVGLF_CDVO

562-596

PVGLF_HRSV1

484-513

PVGLF_HRSVA

484-513

PVGLF_HRSVL

484-513

PVGLF_HRSVR

484-513

PVGLF_MEASE

224-256

451-484

PVGLF_MEASI

227-259

454-487

PVGLF_MEASY

224-256

451-484

PVGLF_MUMPM

446-475

PVGLF_MUMPR

446-474

PVGLF_MUMPS

5-38

446-474

PVGLF_NDVI

132-165

PVGLF_PHODV

531-565

PVGLF_PI1HC

456-484

PVGLF_PI3B

453-481

PVGLF_PI3H4

453-481

PVGLF_RINDK

220-252

447-480

PVGLF_RINDL

220-252

447-480

PVGLF_SEND5

460-488

PVGLF_SENDF

460-488

PVGLF_SENDH

460-488

PVGLF_SENDJ

460-488

PVGLF_SENDZ

460-488

PVGLF_SV5

446-474

PVGLF_TRTV

452-481

PVGLG_HSVEB

327-364

PVGLG_SYNV

524-553

PVGLG_VSVIG

450-488

PVGLG_VSVJO

457-492

PVGLG_VSVO

450-488

PVGLG_VSVSJ

450-488

PVGLH_HCMVA

691-719

PVGLH_HCMVT

690-718

PVGLH_HCV6G

640-677

PVGLH_HSVE4

814-850

PVGLH_HSVEB

807-843

PVGLI_HCMVA

158-194

PVGLM_BUNGE

197-227

438-468

982-1020

1049-1084

PVGLM_BUNL7

190-220

PVGLM_BUNSH

190-220

344-381

PVGLM_BUNYW

193-228

434-472

823-854

PVGLM_DUGBV

244-273

637-672

888-915

935-965

1403-1441

PVGLM_HANTB

610-641

1081-1119

PVGLM_HANTH

188-222

612-643

1082-1120

PVGLM_HANTL

188-222

612-643

1083-1121

PVGLM_HANTV

188-222

612-643

1083-1121

PVGLM_PHV

616-649

1088-1121

PVGLM_PTPV

949-982

1275-1309

PVGLM_PUUMH

620-653

1092-1125

PVGLM_PUUMS

620-653

1092-1125

PVGLM_RVFV

620-653

830-883

PVGLM_RVFVZ

620-653

830-863

1156-1185

PVGLM_SEOUR

605-641

1082-1120

PVGLM_SEOUS

610-641

1081-1119

PVGLM_UUK

431-468

966-995

PVGLF_BEV

1491-1526

PVGLY_JUNIN

12-45

PVGLY_LASSG

237-265

PVGLY_LASSJ

238-288

PVGLY_PIARV

12-50

PVGLY_TACV

12-50

PVGLY_TACV5

12-50

89-124

PVGLY_TACV7

12-50

89-124

PVGLY_TACVT

12-50

89-124

PVGNB_CPMV

1527-1555

PVGNM_BPMV

137-167

280-327

837-888

PVGNM_CPMV

209-242

741-771

PVGNM_CPSMV

60-88

479-515

PVGNM_RCMV

766-799

PVGP2_EBV

78-111

PVGP3_EBV

78-111

PVM1_REOVD

280-318

324-361

PVM1_REOVL

280-318

PVM21_REOVD

168-199

PVM22_REOVD

168-199

PVM2_REOVJ

168-199

PVM2_REOVL

168-199

PVM3_REOVD

333-364

PVMAT_SV5

308-342

PVMTA_TRTV

122-150

PVME1_CVBM

64-102

PVME1

CVHOC

64-102

PVME1_CVMA5

65-103

PVME1_CVMJH

65-103

PVME1_CVTKE

64-102

PVMEM_EBV

178-213

PVMP_CERV

93-126

PVMP_SOCMV

66-98

273-303

PVMSA_HPBDB

201-238

269-302

PVMSA_HPBDC

194-227

268-301

PVMSA_HPBDU

157-190

231-264

PVMSA_HPBDW

194-227

269-302

PVMSA_HPBGS

209-243

271-307

PVMSA_HPBHE

159-195

236-269

PVMSA_HPBV0

70-98

PVMSA_HPVB2

244-272

PVMSA_HPVB4

244-272

PVMSA_HPBV9

244-272

PVMSA_HPBVA

233-261

PVMSA_HPBVD

70-98

PVMSA_HPBVI

233-261

PVMSA_HPBVJ

233-261

PVMSA_HPBVL

233-261

PVMSA_HPBVN

70-98

PVMSA_HPBVO

233-261

PVMSA_HPBVP

244-272

PVMSA_HPBVR

244-272

PVMSA_HPBVS

70-98

PVMSA_HPBVW

233-261

PVMSA_HPBVY

233-261

PVMSA_HPBVZ

233-261

PVMSA_WHV1

207-241

269-305

PVMSA_WHV59

212-246

274-310

PVMSA_WHV7

212-246

274-310

PVMSA_WHV8

212-246

274-310

PVMSA_WHV81

212-246

274-310

PVMSA_WHVW6

125-161

PVMT2

—L IAZI1

10-44

PVMT8_MYXVL

5-34

141-170

PVMT9_MYXVL

246-282

5.3. Synthesis of Peptides

The peptides of the invention may be synthesized or prepared by techniques well known in the art. See, for example, Creighton, 1983, Proteins: Structures and Molecular Principles, W.H. Freeman and Co., NY, which is incorporated herein by reference in its entirety. Short peptides, for example, can be synthesized on a solid support or in solution. Longer peptides amy be made using recombinant DNA techniques. Here, the nucleotide sequences encoding the peptides of the invention may be synthesized, and/or cloned, and expressed according to techniques well known to those of ordinary skill in the art. See, for example, Sambrook, et al., 1989, Molecular Cloning, A Laboratory Manual, Vols. 1-3, Cold Spring Harbor Press, N.Y.

The peptides of the invention may alternatively be synthesized such that one or more of the bonds which link the amino acid residues of the peptides are non-peptide bonds. These alternative non-peptide bonds may be formed by utilizing reactions well known to those in the art, and may include, but are not limited to imino, ester, hydrazide, semicarbazide, and azo bonds, to name but a few. In yet another embodiment of the invention, peptides comprising the sequences described above may be synthesized with additional chemical groups present at their amino and/or carboxy termini, such that, for example, the stability, bioavailability, and/or inhibitory activity of the peptides is enhanced. For example, hydrophobic groups such as carbobenzoxyl, dansyl, or t-butyloxycarbonyl groups, may be added to the peptides' amino termini. Likewise, an acetyl group or a 9-fluorenylmethoxy-carbonyl group may be placed at the peptides' amino termini. (See “X” in Tables I to IV, above.) Additionally, the hydrophobic group, t-butyloxycarbonyl, or an amido group may be added to the peptides' carboxy termini. (See “Z” in Tables I to IV, above.) Further, the peptides of the invention may be synthesized such that their steric configuration is altered. For example, the D-isomer of one or more of the amino acid residues of the peptide may be used, rather than the usual L-isomer. Still further, at least one of the amino acid residues of the peptides of the invention may be substituted by one of the well known non-naturally occurring amino acid residues. Alterations such as these may serve to increase the stability, bioavailability and/or inhibitory action of the peptides of the invention.

Any of the peptides described above may, additionally, have a non-peptide macromolecular carrier group covalently attached to their amino and/or carboxy termini. Such macromolecular carrier groups may include, for example, lipid-fatty acid conjugates, polyethylene glycol, or carbohydrates. “X”, in Tables I to IV, above, may therefore additionally represent any of the above macromolecular carrier groups covalently attached to the amino terminus of a peptide. Likewise, “Z”, in Tables I to IV, may additionally represent any of the macromolecular carrier groups described above.

5.4. Assays for Antiviral Activity

The antiviral activity exhibited by the peptides of the invention may be measured, for example, by easily performed in vitro assays, such as those described below, which can test the peptides' ability to inhibit syncytia formation, or their ability to inhibit infection by cell-free virus. Using these assays, such parameters as the relative antiviral activity of the peptides, exhibit against a given strain of virus and/or the strain specific inhibitory activity of the peptide can be determined. A cell fusion assay may be utilized to test the peptides' ability to inhibit HIV-induced syncytia formation in vitro. Such an assay may comprise culturing uninfected CD-4

+

cells (such as Molt or CEM cells, for example) in the presence of chronically HIV-infected cells and a peptide to be assayed. For each peptide, a range of peptide concentrations may be tested. This range should include a control culture wherein no peptide has been added. Standard conditions for culturing, well known to those of ordinary skill in the art, are used. After incubation for an appropriate period (24 hours at 37° C., for example) the culture is examined microscopically for the presence of multinucleated giant cells, which are indicative of cell fusion and syncytia formation.

A reverse transcriptase (RT) assay may be utilized to test the peptides' ability to inhibit infection of CD-4

+

cells by cell-free HIV. Such an assay may comprise culturing an appropriate concentration (i.e., TCID

50

) of virus and CD-4

+

cells in the presence of the peptide to be tested. Culture conditions well known to those in the art are used. As above, a range of peptide concentrations may be used, in addition to a control culture wherein no peptide has been added. After incubation for an appropriate period (e.g., 7 days) of culturing, a cell-free supernatant is prepared, using standard procedures, and tested for the present of RT activity as a measure of successful infection. The RT activity may be tested using standard techniques such as those described by, for example, Goff et al. (Goff, S. et al., 1981, J. Virol. 38:239-248) and/or Willey et al. (Willey, R. et al., 1988, J. Virol. 62:139-147). These references are incorporated herein by reference in their entirety.

Standard methods which are well-known to those of skill in the art may be utilized for assaying non-retroviral activity. See, for example, Pringle et al. (Pringle, C. R. et al., 1985, J. Medical Virology 17:377-386) for a discussion of respiratory syncytial virus and parainfluenza virus activity assay techniques. Further, see, for example, “Zinsser Microbiology”, 1988, Joklik, W. K. et al., eds., Appleton & Lange, Norwalk, Conn., 19th ed., for a general review of such techniques. These references are incorporated by reference herein in its entirety.

5.5. Uses of the Peptides of the Invention

The DP-178 (SEQ ID:1) peptides of the invention, and DP-178 fragments, analogs, and homologs, exhibit potent antiviral activity. The DP-107-like and DP-178-like peptides of the invention preferably exhibit antiviral activity. As such, the peptides may be used as inhibitors of human and non-human viral and retroviral, especially HIV, transmission to uninfected cells.

The human retroviruses whose transmission may be inhibited by the peptides of the invention include, but are not limited to all strains of HIV-1 and HIV-2 and the human T-lymphocyte viruses (HTLV-I and II). The non-human retroviruses whose transmission may be inhibited by the peptides of the invention include, but are not limited to bovine leukosis virus, feline sarcoma and leukemia viruses, simian immunodeficiency, sarcoma and leukemia viruses, and sheep progress pneumonia viruses.

Non retroviral viruses whose transmission may be inhibited by the peptides of the invention include, but are not limited to human respiratory syncytial virus, canine distemper virus, newcastle disease virus, human parainfluenza virus, and influenza viruses. Further, any virus or retrovirus containing peptides listed in Tables V through X above, may be inhibited by the peptides of the invention.

As discussed more fully, below, in Section 5.5.1 and in the Example presented, below, in Section 8, DP-107 and DP-178, and DP-107-like and DP-178-like peptides form non-covalent protein-protein interactions which are required for normal activity of the virus. Thus, the peptides of the invention may also be utilized as components in assays for the identification of compounds that interfere with such protein-protein interactions and may, therefore, act as antiviral agents. These assays are discussed, below, in Section 5.5.1.

5.5.1. Antiviral Compound Screening Assays for Compounds that Interact with the PKD1 Gene Product

As demonstrated in the Example presented in Section 8, below, DP-107 and DP-178 portions of the TM protein gp41 form non-covalent protein-protein intereactions. As also demonstrated, the maintenance of such interactions is necessary for normal viral infectivity. Thus, compounds which bind DP-107, bind DP-178, and/or act to disrupt normal DP-107/DP-178 protein-protein interactions may act as patent antiviral agents. Described below are assays for the identification of such compounds. Note that, while, for case and clarity of discussion, DP-107 and DP-178 peptides will be used as components of the assays described, but it is to be understood that any of the DP-107-like or DP-178-like peptides described, above, in Sections 5.1 and 5.2 may also be utilized as part of these screens for antiviral compounds.

Compounds which may be tested for an ability to bind DP-107, DP-178, and/or disrupt DP-107/DP-178 interactions, and which therefore, potentially represent antiviral compounds, include, but are not limited to, peptides made of D- and/or L-configuration amino acids (in, for example, the form of random peptide libraries; see Lam, K. S. et al., 1991, Nature 354:82-84), phosphopeptides (in, for example, the form of random or partially degenerate, directed phosphopeptide libraries; see, for example, Songyang, Z. et al., 1993, Cell 72:767-778), antibodies, and small organic or inorganic molecules. Synthetic compounds, natural products, and other sources of potentially effective materials may be screened in a variety of ways, as described in this Section. The compounds, antibodies, or other molecules identified may be tested for an ability to inhibit viral activity, utilizing, for example, viral assays such as those described, above, in Section 5.4.

Among the peptides which may be tested are soluble peptides comprising DP-107 and/or DP-178 domains, and peptides comprising DP-107 and/or DP-178 domains having one or more mutations within one or both of the domains, such as the M41-P peptide described, below, in the Example presented in Section 8, which contains a isoleucine to proline mutation within the DP-178 sequence.

In one embodiment of such screening methods is a method for identifying a compound to be tested for antiviral ability comprising:

(a) exposing at least one compound to a peptide comprising a DP-107 peptide for a time sufficient to allow binding of the compound to the DP-107 peptide;

(b) removing non-bound compounds; and

(c) determining the presence of the compound bound to the DP-107 peptide, thereby identifying an agent to be tested for antiviral ability.

In a second embodiment of such screening methods is a method for identifying a compound to be tested for antiviral ability comprising:

(a) exposing at least one compound to a peptide comprising a DP-178 peptide for a time sufficient to allow binding of the compound to the DP-178 peptide;

(b) removing non-bound compounds; and

(c) determining the presence of the compound bound to the DP-178 peptide, thereby identifying an agent to be tested for antiviral ability.

One method utilizing these types of approaches that may be pursued in the isolation of such DP-107-binding or DP-178-binding compounds is an assay which would include the attachment of either the DP-107 or the DP-178 peptide to a solid matrix, such as, for example, agarose or plastic beads, microtiter plate wells, petri dishes, or membranes composed of, for example, nylon or nitrocellulose. In such an assay system, either the DP-107 or DP-178 protein may be anchored onto a solid surface, and the compound, or test substance, which is not anchored, is labeled, either directly or indirectly. In practice, microtiter plates are conveniently utilized. The anchored component may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished simply by coating the solid surface with a solution of the protein and drying. Alternatively, an immobilized antibody, preferably a monoclonal antibody, specific for the protein may be used to anchor the protein to the solid surface. The surfaces may be prepared in advance and stored.

In order to conduct the assay, the labeled compound is added to the coated surface containing the anchored DP-107 or DP-178 peptide. After the reaction is complete, unreacted components are removed (e.g., by washing) under conditions such that any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the compound is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the labeled component is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the compound (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody).

Alternatively, such an assay can be conducted in a liquid phase, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for DP-107 or DP-178, whichever is appropriate for the given assay, or ab antibody specific for the compound, i.e., the test substance, in order to anchor any complexes formed in solution, and a labeled antibody specific for the other member of the complex to detect anchored complexes.

By utilizing procedures such as this, large numbers of types of molecules may be simultaneously screened for DP-107 or DP-178-binding capability, and thus potential antiviral activity.

Further, compounds may be screened for an ability to inhibit the formation of or, alternatively, disrupt DP-107/DP-178 complexes. Such compounds may then be tested for antiviral capability. For ease of description, DP-107 and DP-178 will be referred to as “binding partners.” Compounds that disrupt such interactions may exhibit antiviral activity. Such compounds may include, but are not limited to molecules such as antibodies, peptides, and the like described above.

The basic principle of the assay systems used to identify compounds that interfere with the interaction between the DP-107 and DP-178 peptides involves preparing a reaction mixture containing peptides under conditions and for a time sufficient to allow the two peptides to interact and bind, thus forming a complex. In order to test a compound for disruptive activity, the reaction is conducted in the presence and absence of the test compound, i.e., the test compound may be initially included in the reaction mixture, or added at a time subsequent to the addition of one of the binding partners; controls are incubated without the test compound or with a placebo. The formation of any complexes between the binding partners is then detected. The formation of a complex in the control reaction, but not in the reaction mixture containing the test compound indicates that the compound interferes with the interaction of the DP-107 and DP-178 peptides.

The assay for compounds that interfere with the interaction of the binding partners can be conducted in a heterogeneous or homogeneous format. Heterogeneous assays involve anchoring one of the binding partners onto a solid phase and detecting complexes anchored on the solid phase at the end of the reaction. In homogeneous assays, the entire reaction is carried out in a liquid phase. In either approach, the order of addition of reactants can be varied to obtain different information about the compounds being tested. For example, test compounds that interfere with the interaction between the binding partners, e.g., by competition, can be identified by conducting the reaction in the presence of the test substance; i.e., by adding the test substance to the reaction mixture prior to or simultaneously with the binding partners. On the other hand, test compounds that disrupt preformed complexes, e.g. compounds with higher binding constants that displace one of the binding partners from the complex, can be tested by adding the test compound to the reaction mixture after complexes have been formed. The various formats are described briefly below.

In a heterogeneous assay system, one binding partner, e.g., either the DP-107 or DP-178 peptide, is anchored onto a solid surface, and its binding partner, which is not anchored, is labeled, either directly or indirectly. In practice, microtiter plates are conveniently utilized. The anchored species may be immobilized by non-covalent or covalent attachments. Non-covalent attachment may be accomplished simply by coating the solid surface with a solution of the protein and drying. Alternatively, an immobilized antibody specific for the protein may be used to anchor the protein to the solid surface. The surfaces may be prepared in advance and stored.

In order to conduct the assay, the binding partner of the immobilized species is added to the coated surface with or without the test compound. After the reaction is complete, unreacted components are removed (e.g., by washing) and any complexes formed will remain immobilized on the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of ways. Where the binding partner was pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the binding partner is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface; e.g., using a labeled antibody specific for the binding partner (the antibody, in turn, may be directly labeled or indirectly labeled with a labeled anti-Ig antibody). Depending upon the order of addition of reaction components, test compounds which inhibit complex formation or which disrupt preformed complexes can be detected.

Alternatively, the reaction can be conducted in a liquid phase in the presence or absence of the test compound, the reaction products separated from unreacted components, and complexes detected; e.g., using an immobilized antibody specific for one binding partner to anchor any complexes formed in solution, and a labeled antibody specific for the other binding partner to detect anchored complexes. Again, depending upon the order of addition of reactants to the liquid phase, test compounds which inhibit complex or which disrupt preformed complexes can be identified.

In an alternate embodiment of the invention, a homogeneous assay can be used. In this approach, a preformed complex of the DP-107 and DP-178 peptides is prepared in which one of the binding partners is labeled, but the signal generated by the label is quenched due to complex formation (see, e.g., U.S. Pat. No. 4,109,496 by Rubenstein which utilizes this approach for immunoassays). The addition of a test substance that competes with and displaces one of the binding partners from the preformed complex will result in the generation of a signal above background. In this way, test substances which disrupt DP-107/DP-178 protein-protein interaction can be identified.

5.6 Pharmaceutical Formulations, Dosages and Modes of Administration

With respect to HIV, the peptides of the invention may be used as a therapeutic in the treatment of AIDS. The peptides of the invention may be administered using techniques well known to those in the art. Preferably, agents are formulated and administered systemically. Techniques for formulation and administration may be found in “Remington's Pharmaceutical Sciences”, 18th ed., 1990, Mack Publishing Co., Easton, Pa. Suitable routes may include oral, rectal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections, just to name a few. Most preferably, administration is intravenous. For injection, the agents of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks' solution, Ringer's solution, or physiological saline buffer. For such transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

In addition, the peptides may be used as a prophylactic measure in previously uninfected individuals after acute exposure to an HIV virus. Examples of such prophylactic use of the peptides may include, but are not limited to, prevention of virus transmission from mother to infant and other settings where the likelihood of HIV transmission exists, such as, for example, accidents in health care settings wherein workers are exposed to HIV-containing blood products. The peptides of the invention in such cases may serve the role of a prophylactic vaccine, wherein the host raises antibodies against the peptides of the invention, which then serve to neutralize HIV viruses by, for example, inhibiting further HIV infection. Administration of the peptides of the invention as a prophylactic vaccine, therefore, would comprise administering to a host a concentration of peptides effective in raising an immune response which is sufficient to neutralize HIV, by, for example, inhibiting HIV ability to infect cells. The exact concentration will depend upon the specific peptide to be administered, but may be determined by using standard techniques for assaying the development of an immune response which are well known to those of ordinary skill in the art. The peptides to be used as vaccines are usually administered intramuscularly.

The peptides may be formulated with a suitable adjuvant in order to enhance the immunological response. Such adjuvants may include, but are not limited to mineral gels such as aluminum hydroxide; surface active substances such as lysolecithin, pluronic polyols, polyanions; other peptides; oil emulsions; and potentially useful human adjuvants such as BCG and Corynebacterium parvum. Many methods may be used to introduce the vaccine formulations described here. These methods include but are not limited to oral, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, and intranasal routes.

Alternatively, an effective concentration of polyclonal or monoclonal antibodies raised against the peptides of the invention may be administered to a host so that no uninfected cells become infected by HIV. The exact concentration of such antibodies will vary according to each specific antibody preparation, but may be determined using standard techniques well known to those of ordinary skill in the art. Administration of the antibodies may be accomplished using a variety of techniques, including, but not limited to those described in this section.

Effective dosages of the peptides of the invention to be administered may be determined through procedures well known to those in the art which address such parameters as biological half-life, bioavailability, and toxicity. Given the data presented below in Section 6, DP-178, for example, may prove efficacious in vivo at doses required achieve circulating levels of long per ml of peptide.

A therapeutically effective dose refers to that amount of the compound sufficient to result in amelioration of symptoms or a prolongation of survival in a patient. Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. Compounds which exhibit large therapeutic indices are preferred. The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal disruption of the PTK/adaptor protein complex, or a half-maximal inhibition of the cellular level and/or activity of a complex component) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography (HPLC).

The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. (See e.g. Fingl et al., 1975, in “The Pharmacological Basis of Therapeutics”, Ch. 1 p1).

It should be noted that the attending physician would know how to and when to terminate, interrupt, or adjust administration due to toxicity, or to organ dysfunctions. Conversely, the attending physician would also know to adjust treatment to higher levels if the clinical response were not adequate (precluding toxicity). The magnitude of an administrated dose in the management of the oncogenic disorder of interest will vary with the severity of the condition to be treated and to the route of administration. The dose and perhaps dose frequency, will also vary according to the age, body weight, and response of the individual patient. A program comparable to that discussed above may be used in veterinary medicine.

As demonstrated in the Example presented below in Section 6, the antiviral activity of the peptides of the invention may show a pronounced type and subtype specificity, i.e., specific peptides may be effective in inhibiting the activity of only specific viruses. This feature of the invention presents many advantages. One such advantage, for example, lies in the field of diagnostics, wherein one can use the antiviral specificity of the peptide of the invention to ascertain the identity of a viral isolate. With respect to HIV, one may easily determine whether a viral isolate consists of an HIV-1 or HIV-2 strain. For example, uninfected CD-4

+

cells may be co-infected with an isolate which has been identified as containing HIV the DP-178 (SEQ ID:1) peptide, after which the retroviral activity of cell supernatents may be assayed, using, for example, the techniques described above in Section 5.2. Those isolates whose retroviral activity is completely or nearly completely inhibited contain HIV-1. Those isolates whose viral activity is unchanged or only reduced by a small amount, may be considered to not contain HIV-1. Such an isolate may then be treated with one or more of the other DP-178 peptides of the invention, and subsequently be tested for its viral activity in order to determine the identify of the viral isolate.

Use of pharmaceutically acceptable carriers to formulate the compounds herein disclosed for the practice of the invention into dosages suitable for systemic administration is within the scope of the invention. With proper choice of carrier and suitable manufacturing practice, the compositions of the present invention, in particular, those formulated as solutions, may be administered parenterally, such as by intravenous injection. The compounds can be formulated readily using pharmaceutically acceptable carriers well known in the art into dosages suitable for oral administration. Such carriers enable the compounds of the invention to be formulated as tablets, pills, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated.

Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredients are contained in an effective amount to achieve its intended purpose. Determination of the effective amounts is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.

In addition to the active ingredients, these pharmaceutical compositions may contain suitable pharmaceutically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. The preparations formulated for oral administration may be in the form of tablets, dragees, capsules, or solutions.

The pharmaceutical compositions of the present invention may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.

Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.

Pharmaceutical preparations for oral use can be obtained by combining the active compounds with solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.

Pharmaceutical preparations which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added.

6. EXAMPLE

DP-178 (SEQ ID:1) is a Potent Inhibitor of HIV-1 Infection

In this example, DP-178 (SEQ ID:1) is shown to be a potent inhibitor of HIV-1 mediated CD-4

+

cell-cell fusion and infection by cell free virus. In the fusion assay, this peptide completely blocks virus induced syncytia formation at concentrations of from 1-10 ng/ml. In the infectivity assay the inhibitory concentration is somewhat higher, blocking infection at 90 ng/ml. It is further shown that DP-178 (SEQ ID:1) shows that the antiviral activity of DP-178 (SEQ ID:1) is highly specific for HIV-1. Additionally, a synthetic peptide, DP-185 (SEQ ID:3), representing a HIV-1-derived DP-178 homolog is also found to block HIV-1-mediated syncytia formation.

6.1. Materials and Methods

6.1.1. Peptide Synthesis

Peptides were synthesized using Fast Moc chemistry on an Applied Biosystems Model 431A peptide synthesizer. Amidated peptides were prepared using Rink resin (Advanced Chemtech) while peptides containing free carboxy termini were synthesized on Wang (p-alkoxy-benzyl-alcohol) resin (Bachem). First residues were double coupled to the appropriate resin and subsequent residues were single coupled. Each coupling step was followed by acetic anhydride capping. Peptides were cleaved from the resin by treatment with trifluoracetic acid (TFA) (10 ml), H

2

O (0.5 ml), thioanisole (0.5 ml), ethanedithiol (0.25 ml), and crystalline phenol (0.75 g). Purification was carried out by reverse phase HPLC. Approximately 50 mg samples of crude peptide were chromatographed on a Waters Delta Pak C18 column (19mm×30 cm, 15μ spherical) with a linear gradient; H

2

O/acetonitrile 0.1% TFA. Lyophilized peptides were stored desiccated and peptide solutions were made in water at about 1 mg/ml. Electrospray mass spectrometry yielded the following results: DP-178 (SEQ ID:1):4491.87 (calculated 4491.94); DP-180 (SEQ ID:2):4491.45 (calculated 4491.94); DP-185 (SEQ ID:3):not done (calculated 4546.97).

6.1.2. Virus

The HIV-1

LAI

virus was obtained from R. Gallo (Popovic, M. et al., 1984, Science 224:497-508) and propagated in CEM cells cultured in RPMI 1640 containing 10% fetal calf serum. Supernatant from the infected CEM cells was passed through a 0.2 μm filter and the infectious titer estimated in a microinfectivity assay using the AA5 cell line to support virus replication. For this purpose, 25 μl of serial diluted virus was added to 75 μl AA5 cells at a concentration of 2×10

5

/ml in a 96-well microtitre plate. Each virus dilution was tested in triplicate. Cells were cultured for eight days by addition of fresh medium every other day. On day 8 post infection, supernatant samples were tested for virus replication as evidenced by reverse transcriptase activity released to the supernatant. The TCID

50

was calculated according to the Reed and Muench formula (Reed, L. J. et al., 1938, Am. J. Hyg. 27:493-497). The titer of the HIV-1

LAI

and HIV-1

MN

stocks used for these studies, as measured on the AA5 cell line, was approximately 1.4×106 and 3.8×10

4

TCID

50

/ml, respectively.

6.1.3. Cell Fusion Assay

Approximately 7×10

4

Molt cells were incubated with 1×10

4

CEM cells chronically infected with the HIV-1

LAI

virus in 96-well plates (one-half area cluster plates; Costar, Cambridge, Mass.) in a final volume of 100 μl culture medium as previously described (Matthews, T. J. et al., 1987, Proc. Natl. Acad. Sci. USA 84: 5424-5428). Peptide inhibitors were added in a volume of 10 μl and the cell mixtures were incubated for 24 hr. at 37° C. At that time, multinucleated giant cells were estimated by microscopic examination at a 40× magnification which allowed visualization of the entire well in a single field.

6.1.4. Cell Free Virus Infection Assay

Synthetic peptides were incubated at 37° C. with either 247 TCID

50

(for experiment depicted in FIG.

2

), or 62 TCID

50

(for experiment depicted in

FIG. 3

) units of HIV-1

LAI

virus or 25 TCID

50

units of HIV-2

NIH2

and CEM CD4

+

cells at peptide concentrations of 0, 0.04, 0.4, 4.0, and 40 μg/ml for 7 days. The resulting reverse transcriptase (RT) activity in counts per minute was determined using the assay described, below, in Section 6.1.5. See, Reed, L. J. et al., 1938, Am. J. Hyg. 27: 493-497 for an explanation of TCID

50

calculations.

6.1.5. Reverse Transcriptase Assay

The micro-reverse transcriptase (RT) assay was adapted from Goff et al. (Goff, S. et al., 1981, J. Virol. 38:239-248) and Willey et al. (Willey, R. et al., 1988, J. Virol. 62:139-147). Supertanants from virus/cell cultures are adjusted to 1% Triton-X100. A 10 μl sample of supernatant was added to 50 μl of RT cocktail in a 96-well U-bottom microtitre plate and the samples incubated at 37° C. for 90 min. The RT cocktail contained 75 mM KCl, 2 mM dithiothreitol, 5 mM MgCl

2

, 5 μg/ml poly A (Pharmacia, cat. No. 27-4110-01), 0.25 units/ml oligo dT (Pharmacia, cat. No. 27-7858-01), 0.05% NP40, 50 mM Tris-HCl, pH 7.8, 0.5 μM non-radioactive dTTP, and 10 μCi/ml

32

P-dTTP (Amersham, cat. No. PB.10167).

After the incubation period, 40 μl of reaction mixture was applied to a Schleicher and Schuell (S+S) NA45 membrane (or DE81 paper) saturated in 2×SSC buffer (0.3M NaCl and 0.003M sodium citrate) held in a S+S Minifold over one sheet of GB003 (S+S) filter paper, with partial vacuum applied. Each well of the minifold was washed four times with 200 μl 2×SSC, under full vacuum. The membrane was removed from the minifold and washed 2 more times in a pyrex dish with an excess of 2×SSC. Finally, the membrane was drained on absorbent paper, placed on Whatman #3 paper, covered with Saran wrap, and exposed to film overnight at −70° C.

6.2. Results

6.2.1. Peptide Inhibition of Infected Cell-induced Syncytia Formation

The initial screen for antiviral activity assayed peptides' ability to block syncytium formation induced by overnight co-cultivation of uninfected Molt4 cells with chronically HIV-1 infected CEM cells. The results of several such experiments are presented herein. In the first of these experiments, serial DP-178 (SEQ ID:1) peptide concentrations between 10 μg/ml and 12.5 ng/ml were tested for blockade of the cell fusion process. For these experiments, CEM cells chronically infected with either HIV-1

LAI

, HIV-1

MN

, HIV-1

RF

, or HIV-1

SF2

virus were cocultivated overnight with uninfected Molt 4 cells. The results (

FIG. 4

) show that DP-178 (SEQ ID:1) afforded complete protection against each of the HIV-1 isolates down to the lowest concentration of DP-178 (SEQ ID:1) used. For HIV

LAI

inhibition, the lowest concentration tested was 12.5 ng/ml; for all other HIV-1 viruses, the lowest concentration of DP-178 (SEQ ID:1) used in this study was 100 ng/ml. A second peptide, DP-180 (SEQ ID:2), containing the same amino acid residues as DP-178 (SEQ ID:1) but arranged in a random order exhibited no evidence of anti-fusogenic activity even at the high concentration of 40 μg/ml (FIG.

4

). These observations indicate that the inhibitory effect of DP-178 (SEQ ID:1) is primary sequence-specific and not related to non-specific peptide/protein interactions. The actual endpoint (i.e., the lowest effective inhibitory concentration) of DP-178 inhibitory action is within the range of 1-10 ng/ml.

The next series of experiments involved the preparation and testing of a DP-178 (SEQ ID:1) homolog for its ability to inhibit HIV-1-induced syncytia formation. As shown in

FIG. 1

, the sequence of DP-185 (SEQ ID:3) is slightly different from DP-178 (SEQ ID:1) in that its primary sequence is taken from the HIV-1

SF2

isolate and contains several amino acid differences relative to DP-178 (SEQ ID:1) near the N terminus. As shown in

FIG. 4

, DP-185 (SEQ ID:3), exhibits inhibitory activity even at 312.5 ng/ml, the lowest concentration tested.

The next series of experiments involved a comparison of DP-178 (SEQ ID:1) HIV-1 and HIV-2 inhibitory activity. As shown in

FIG. 5

, DP-178 (SEQ ID:1) blocked HIV-1-mediated syncytia formation at peptide concentrations below 1 ng/ml. DP-178 (SEQ ID:1) failed, however, to block HIV-2 mediated syncytia formation at concentrations as high as 10 μg/ml. This striking 4 log selectivity of DP-178 (SEQ ID:1) as an inhibitor of HIV-1-mediated cell fusion demonstrates an unexpected HIV-1 specificity in the action of DP-178 (SEQ ID:1). DP-178 (SEQ ID:1) inhibition of HIV-1-mediated cell fusion, but the peptide's inability to inhibit HIV-2 medicated cell fusion in the same cell type at the concentrations tested provides further evidence for the high degree of selectivity associated with the antiviral action of DP-178 (SEQ ID:1).

6.2.2. Peptide Inhigition of Infection by Cell-free Virus

DP-178 (SEQ ID:1) was next tested for its ability to block CD-4

+

CEM cell infection by cell free HIV-1 virus. The results, shown in

FIG. 2

, are from an experiment in which DP-178 (SEQ ID:1) was assayed for its ability to block infection of CEM cells by an HIV-1

LAI

isolate. Included in the experiment were three control peptides, DP-116 (SEQ ID:9), DP-125 (SEQ ID:8), and DP-118 (SEQ ID:10). DP-116 (SEQ ID:9) represents a peptide previously shown to be inactive using this assay, and DP-125 (SEQ ID:8; Wild, C. et al., 1992, Proc. Natl. Acad, Sci. USA 89:10,537) and DP-118 (SEQ ID:10) are peptides which have previously been shown to be active in this assay. Each concentration (0, 0.04, 0.4, 4, and 40 μg/ml) of peptide was incubated with 247 TCID

50

units of HIV-1

LAI

virus and CEM cells. After 7 days of culture, cell-free supernatant was tested for the presence of RT activity as a measure of successful infection. The results, shown in

FIG. 2

, demonstrate that DP-178 (SEQ ID:1) inhibited the de novo infection process mediated by the HIV-1 viral isolate at concentrations as low as 90 ng/ml (IC50=90 ng/ml). In contrast, the two positive control peptides, DP-125 (SEQ: ID:8) and DP-118 (SEQ ID:10), had over 60-fold higher IC50 concentrations of approximately 5 μg/ml.

In a separate experiment, the HIV-1 and HIV-2 inhibitory action of DP-178 (SEQ ID:1) was tested with CEM cells and either HIV-1

LAI

or HIV-2

NIHZ

. 62 TCID

50

HIV-1

LAI

or 25 GCID

50

HIV-2

NIHZ

were used in these experiments, and were incubated for 7 days. As may be seen in

FIG. 3

, DP-178 (SEQ ID:1) inhibited HIV-1 infection with an IC50 of about 31 ng/ml. In contrast, DP-178 (SEQ ID:1) exhibited a much higher IC50 for HIV-2

NIHZ

, thus making DP-178 (SEQ ID:1) two logs more potent as a HIV-1 inhibitor than a HIV-2 inhibitor. This finding is consistent with the results of the fusion inhibition assays described, above, in Section 6.2.1, and further supports a significant level of selectivity (i.e., for HIV-1 over HIV-2).

7. EXAMPLE

The HIV-1 Inhibitor, DP-178 SEQ ID NO:1, is Non-cytotoxic

In this Example, the 36 amino acid synthetic peptide inhibitor DP-178 (SEQ ID:1) is shown to be non-cytotoxic to cells in culture, even at the highest peptide concentrations (40 μg/ml) tested.

7.1. Materials and Methods

Cell proliferation and toxicity assay: Approximately 3.8×10

5

CEM cells for each peptide concentration were incubated for 3 days at 37° C. in T25 flasks. Peptides tested were DP-178 (SEQ ID:1) and DP-116 (SEQ ID:9), as described in FIG.

1

. The concentrations of each peptide used were 0, 2.5, 10, and 40 μg/ml. Cell counts were taken at incubation times of 0, 24, 48, and 72 hours.

7.2. Results

Whether the potent HIV-1 inhibitor DP-178 (SEQ ID:1) exhibited any cytotoxic effects was assessed by assaying the peptide's effects on the proliferation and viability of cells in culture. CEM cells were incubated in the presence of varying concentrations of DP-178 (SEQ ID:1), and DP-116 (SEQ ID:9), a peptide previously shown to be ineffective as a HIV inhibitor (Wild, C. et al., 1992, Proc. Natl. Acad. Sci. USA 89:10,537-10,541). Additionally, cells were incubated in the absence of either peptide.

The results of the cytotoxicity study demonstrate that DP-178 (SEQ ID: 1) exhibits no cytotoxic effects on cells in culture. As can be seen, below, in Table XI, even the proliferation and viability characteristics of cells cultured for 3 days in the presence of the highest concentration of DP-178 (SEQ ID:1) tested (40 μg/ml) do not significantly differ from the DP-116 (SEQ ID:9) or the no-peptide controls. The cell proliferation data is also represented in graphic form in FIG.

6

. As was demonstrated in the Working Example presented above in Section 6, DP-178 (SEQ ID:1) completely inhibits HIV-1 mediated syncytia formation at peptide concentrations between 1 and 10 ng/ml, and completely inhibits cell-free viral infection at concentrations of at least 90 ng/ml. Thus, this study demonstrates that even at peptide concentrations greater than 3 log higher than the HIV inhibitory dose, DP-178 (SEQ ID:1) exhibits no cytotoxic effects.

TABLE XI

% Viability

Peptide

at time (hours)

Peptide

Concentration μg/ml

0

24

48

72

DP178

40

98

97

95

97

(SEQ

10

98

97

98

98

ID:1)

2.5

98

93

96

96

DP116

40

98

95

98

97

(SEQ

10

98

95

93

98

ID:9)

2.5

98

96

98

99

No

0

98

97

99

98

Peptide

8. EXAMPLE

The Interaction of DP178 and DP107

Soluble recombinant forms of gp41 used in the example described below provide evidence that the DP178 peptide associates with a distal site on gp41 whose interactive structure is influenced by the DP107 leucine zipper motif. A single mutation disrupting the coiled-coil structure of the leucine zipper domain transformed the soluble recombinant gp41 protein from an inactive to an active inhibitor of HIV-1 fusion. This transformation may result from liberation of the potent DP178 domain from a molecular clasp with the leucine zipper, DP107, determinant. The results also indicate that the anti-HIV activity of various gp41 derivatives (peptides and recombinant proteins) may be due to their ability to form complexes with viral gp41 and interfere with its fusogenic process.

8.1. Materials and Methods

8.1.1. Construction of Fusion Proteins and GP41 Mutants

Construction of fusion proteins and mutants shown in

FIG. 7

was accomplished as follows: the DNA sequence corresponding to the extracellular domain of gp41 (540-686) was cloned into the Xmn I site of the expression vector pMal-p2 (New England Biolab) to give M41. The gp41 sequence was amplified from pgtat (Malim et al., 1988, Nature 355: 181-183) by using polymerase chain reaction (PCR) with upstream primer 5′-ATGACGCTGACGGTACAGGCC-3′ (primer A)(SEQ ID:11) and downstream primer 5′-TGACTAAGCTTAATACCACAGCCAATTTGTTAT-3′ (primer B)(SEQ ID:12). M41-P was constructed by using the T7-Gen in vitro mutagenesis kit from United States Biochemicals (USB) following the supplier's instructions. The mutagenic primer (5′-GGAGCTGCTTGGGGCCCCAGAC-3′) introduces (SEQ ID:13) an Ile to Pro mutation in M41 at position 578. M41Δ107 was made using a deletion mutagenic primer 5′-CCAAATCCCCAGGAGCTGCTCGAGCTGCACTATACCAGAC-3′ (primer C)(SEQ ID:14) following the USB T7-Gen mutagenesis protocol. M41Δ178 was made by cloning the DNA fragment corresponding to gp41 amino acids 540-642 into the Xmn I site of pMal-p2. Primer A and 5′-ATAGCTTCTAGATTAATTGTTAATTTCTCTGTCCC-3′ (primer D)(SEQ ID:15) were used in the PCR with the template pgtat to generate the inserted DNA fragments. M41-P was used as the template with primer A and D in PCR to generate M41-PΔ178. All inserted sequences and mutated residues were checked by restriction enzyme analysis and confirmed by DNA sequencing.

8.1.2. Purification and Chatacterization of Fusion Proteins

The fusion proteins were purified according to the protocol described in the manufacturer's brochure of protein fusion and purification systems from New England Biolabs (NEB). Fusion proteins (10 ng) were analyzed by electrophoresis on 8% SDS polyacrylamide gels. Western blotting analysis was performed as described by Sambrook et al, 1989, Molecular Cloning: A Laboratory Manual, 2d Ed, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., Ch. 18, pp. 64-75. An HIV-1 positive serum diluted 1000-fold, or a human Fab derived from repertoire cloning was used to react with the fusion proteins. The second antibody was HRP-conjugated goat antihuman Fab. An ECL Western blotting detection system (Amersham) was used to detect the bound antibody. A detailed protocol for this detection system was provided by the manufacturer. Rainbow molecular weight marker (Amersham) were used to estimate the size of fusion proteins.

8.1.3. Cell Fusion Assays for Anti-HIV Activity

Cell fusion assays were performed as previously described (Matthews et al., 1987, Proc. Natl. Acad. Sci. USA 84: 5424-5481). CEM cells (7×10

4

) were incubated with HIV-1

IIIB

. chronically infected CEM cells (10

4

) in 96-well flat-bottomed half-area plates (Costar) in 100 μl culture medium. Peptide and fusion proteins at various concentrations in 10 μl culture medium were incubated with the cell mixtures at 37° C. for 24 hours. Multinucleated syncytia were estimated with microscopic examination. Both M41 and M41-P did not show cytotoxicity at the concentrations tested and shown in FIG.

8

.

Inhibition of HIV-1 induced cell-cell fusion activity was carried out in the presence of 10 nM DP178 and various concentrations of M41Δ178 or M41-PΔ178 as indicated in FIG.

9

. There was no observable syncytia in the presence of 10 nM DP178. No peptide or fusion protein was added in the control samples.

8.1.4. ELISA Analysis of DP178 Binding to the Leucine Zipper Motif of GP41

The amino acid sequence of DP178 used is: YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF. For enzyme linked immunoassay (ELISA), M41Δ178 or M41-PΔ178 (5 μg/ml) in 0.1M NaHCO

3

, pH 8.6, were coated on 96 wells Linbro ELISA plates (Flow Lab, Inc.) overnight. Each well was washed three times with distilled water then blocked with 3% bovine serum albumin (BSA) for 2 hours. After blocking, peptides with 0.5% BSA in TBST (40 mM Tris-HCl pH7.5, 150 mM NaCl, 0.05% Tween 20) were added to the ELISA plates and incubated at room temperature for 1 hour. After washing three times with TBST, Fab-d was added at a concentration of 10 ng/ml with 0.5% BSA in TBST. The plates were washed three times with TBST after incubation at room temperature for 1 hour. Horse radish peroxidase (HRP) conjugated goat antihuman Fab antiserum at a 2000 fold dilution in TBST with 0.5% BSA was added to each well and incubated at room temperature for 45 minutes. The plates were then washed four times with TBST. The peroxidase substrate o-phenylene diamine (2.5 mg/ml) and 0.15% H

2

O

2

were added to develop the color. The reaction was stopped with an equal volume of 4.5 N H

2

SO

4

after incubation at room temperature for 10 minutes. The optical density of the stopped reaction mixture was measured with a micro plate reader (Molecular Design) at 490 nm. Results are shown in FIG.

10

.

8.2. Results

8.2.1. The Expression and Characterization of the Ectodomain of GP41

As a step toward understanding the roles of the two helical regions in gp41 structure and function, the ectodomain of gp41 was expressed as a maltose binding fusion protein (M41) (FIG.

7

). The fusogenic peptide sequence at the N-terminal of gp41 was omitted from this recombinant protein and its derivatives to improve solubility. The maltose binding protein facilitated purification of the fusion proteins under relatively mild, non-denaturing conditions. Because the M41 soluble recombinant gp41 was not glycosylated, lacked several regions of the transmembrane protein (i.e., the fusion peptide, the membrane spanning, and the cytoplasmic domains), and was expressed in the absence of gp120, it was not expected to precisely reflect the structure of native gp41 on HIV-1 virions. Nevertheless, purified M41 folded in a manner that preserved certain discontinuous epitopes as evidenced by reactivity with human monoclonal antibodies, 98-6, 126-6, and 50-69, previously shown to bind conformational epitopes on native gp41 expressed in eukaryotic cells (Xu et al., 1991, J. Virol. 65: 4832-4838; Chen, 1994, J. Virol. 68:2002-2010). Thus, at least certain regions of native gp41 defined by these antibodies appear to be reproduced in the recombinant fusion protein M41. Furthermore, M41 reacted with a human recombinant Fab (Fab-d) that recognizes a conformational epitope on gp41 and binds HIV-1 virions as well as HIV-1 infected cells but not uninfected cells as analyzed by FACS. Deletion of either helix motif, i.e., DP107 or DP178, of the M41 fusion protein eliminated reactivity with Fab-d. These results indicate that both helical regions, separated by 60 amino acids in the primary sequence, are required to maintain the Fab-d epitope.

8.2.2. Anti-HIV Activity of the Recombinant Ectodomain of GP41

The wild type M41 fusion protein was tested for anti-HIV-1 activity. As explained, supra, synthetic peptides corresponding to the leucine zipper (DP107) and the C-terminal putative helix (DP178) show potent anti-HIV activity. Despite inclusion of both these regions, the recombinant M41 protein did not affect HIV-1 induced membrane fusion at concentrations as high as 50 AM (Table XII, below).

TABLE XII

DISRUPTION OF THE LEUCINE ZIPPER OF

GP41 FREES THE ANTI-HIV MOTIF

DP107

DP178

M41

M41-P

M41-PΔ178

Cell fusion

1 μM

1 nM

>50 μM

83 nM

>50 μM

(IC

90

)

Fab-D

—

—

3.5 × 10

−9

2.5 × 10

−8

—

binding (k

D

)

HIV infectiv-

1 μM

80 nM

>16 μM

66 nM

>8 μM

ity (IC

90

)

1 The affinity constants of Fab-d binding to the fusion proteins were determined using a protocol described by B. Friguet et al., 1985, J. Immunol. Method. 77:305-319.

— = No detectable binding of Fab-d to the fusion proteins.

Antivirul Infectivity Assays. 20 μl of serially diluted virus stock was incubated for 60 minutes at ambient temperature with 20 μl of the indicated concentration of purified recombinant fusion protein in RPMI 1640 containing 10% fetal bovine serum and antibiotics in a 96-well microtiter plate. 20 μl of CEM4 cells at 6×10

5

cells/ml were added to each well, and cultures were incubated at 37° C in a humidified CO

2

incubator. Cells were cultured for 9 postinfection, supernatant samples were assayed for reverse transcriptase (RT) activity, as described below, to monitor viral replication. The 50% tissue culture infectious dose (TCID

50

) was calculated for each condition according to the formula of Reed & Muench, 1937, Am. J. Hyg. 27:493-497. RT activity was determined by a modification of the published methods of Goff et al., 1981, J. Virol. 38:239-248 and Willey et al., 1988, J. Virol. 62:139-147 as described in Chen et al., 1993, AIDS Res. Human Retroviruses 9:1079-1086.

Surprisingly, a single amino acid substitution, proline in place of isoleucine in the middle of the leucine zipper motif, yielded a fusion protein (M41-P) which did exhibit antiviral activity (Table XII and FIG.

8

). As seen in Table XII, M41-P blocked syncytia formation by 90% at approximately 85 nM and neutralized HIV-1

IIIB

infection by 90% at approximately 70 nM concentrations. The anti-HIV-1 activity of M41-P appeared to be mediated by the C-terminal helical sequence since deletion of that region from M41-P yielded an inactive fusion protein, M41-PΔ178 (Table XII). That interpretation was reinforced by experiments demonstrating that a truncated fusion protein lacking the DP178 sequence, M41Δ178, abrogated the potent anti-fusion activity of the DP178 peptide in a concentration-dependent manner (FIG.

9

). The same truncated fusion protein containing the proline mutation disrupting the leucine zipper, M41-PΔ178, was not active in similar competition experiments (FIG.

9

). The results indicate that the DP178 peptide associates with a second site on gp41 whose interactive structure is dependent on a wild type leucine zipper sequence. A similar interaction may occur within the wild type fusion protein, M41, and act to form an intramolecular clasp which sequesters the DP178 region, making it unavailable for anti-viral activity.

A specific association between these two domains is also indicated by other human monoclonal Fab-d studies. For example, Fab-d failed to bind either the DP178 peptide or the fusion protein M41Δ178, but its epitope was reconstituted by simply mixing these two reagents together (FIG.

10

). Again, the proline mutation in the leucine zipper domain of the fusion protein, M41-PΔ178, failed to reconstitute the epitope in similar mixing experiments.

9. EXAMPLE

Method for Computer-Assisted Identification of DP-107-like and DP-178-like Sequences

A number of known coiled-coil sequences have been well described in the literature and contain heptad repeat positioning for each amino acid. Coiled-coil nomenclature labels each of seven amino acids of a heptad repeat A through G, with amino acids A and D tending to be hydrophobic positions. Amino acids E and G tend to be charged. These four positions (A, D, E, and G) form the amphipathic backbone structure of a monomeric alpha-helix. The backbones of two or more amphipathic helices interact with each other to form di-, tri-, tetrameric, etc., coiled-coil structures. In order to begin to design computer search motifs, a series of well characterized coiled coils were chosen including yeast transcription factor GCN4 (SEQ ID:20), Influenza Virus hemagglutinin loop 36 (SEQ ID:24), and human proto-oncogenes c-Myc (SEQ ID:23), c-Fos (SEQ ID:21), and c-Jun (SEQ ID:22). For each peptide sequence, a strict homology for the A and D positions, and a list of the amino acids which could be excluded for the B, C, E, F, and G positions (because they are not observed in these positions) was determined. Motifs were tailored to the DP-107 and DP-178 sequences by deducing the most likely possibilities for heptad positioning of the amino acids of HIV-1 Bru DP-107, which is known to have coiled-coil structure, and HIV-1 Bru DP-178, which is still structurally undefined. The analysis of each of the sequences is contained in FIG.

12

. For example, the motif for GCN4 was designed as follows:

1. The only amino acids (using standard single letter amino acid codes) found in the A or D positions of GCN4 were [LMNV].

2. All amino acids were found at B, C, E, F, and G positions except {CFGIMPTW}.

3. The PESEARCH motif would, therefore, be written as follows:

[LMNV]-{CFGIMPTW} (2)-[LMNV]-{CFGIMPTW} (3)-

[LMNV]-{CFGIMPTW} 2)-[LMNV]-{CFGIMPTW} 3)-

[LMNV]-{CFGIMPTW} 2)-[LMNV]-{CFGIMPTW} 3)-

[LMNV]-{CFGIMPTW} 2)-[LMNV]-{CFGIMPTW} 3)

Translating or reading the motif: “at the first A position either L, M, N, or V must occur; at positions B and C (the next two positions) accept everything except C, F, G, I, M, P, T, or W; at the D position either L, M, N, or V must occur; at positions E, F, and G (the next 3 positions) accept everything except C, F, G, I, M, P, T, or W.” This statement is contained four times in a 28-mer motif and five times in a 35-mer motif. The basic motif key then would be: [LMNV]-{CFGIMPTW}. The motif keys for the remaining well described coiled-coil sequences are summarized in FIG.

12

.

The motif design for DP-107 and DP-178 was slightly different than the 28-mer model sequences described above due to the fact that heptad repeat positions are not defined and the peptides are both longer than 28 residues.

FIG. 13

illustrates several possible sequence alignments for both DP-107 and DP-178 and also includes motif designs based on 28-mer, 35

−mer

, and full-length peptides. Notice that only slight differences occur in the motifs as the peptides are lengthened. Generally, lengthening the base peptide results in a less stringent motif. This is very useful in broadening the possibilities for identifying DP-107-or DP-178-like primary amino acid sequences referred to in this document as “hits”.

In addition to making highly specific motifs for each type peptide sequence to be searched, it is also possible to make “hybrid” motifs. These motifs are made by “crossing” two or more very stringent motifs to make a new search algorithm which will find not only both “parent” motif sequences but also any peptide sequences which have similarities to one, the other, or both “parents”. For example, in Table 3 the “parent” sequence of GCN4 is crossed with each of the possible “parent” motifs of DP-107. Now the hybrid motif must contain all of the amino acids found in the A and D positions of both parents, and exclude all of the amino acids not found in either parent at the other positions. The resulting hybrid from crossing GCN4 or [LMNV] {CFGIMPTW} and DP-107 (28-mer with the first L in the D position) or [ILQT] {CDFIMPST}, is [ILMNQTV] {CFIMPT}. Notice that now only two basic hybrid motifs exist which cover both framing possibilities, as well as all peptide lengths of the parent DP-107 molecule.

FIG. 15

represents the hybridizations of GCN4 with DP-178.

FIG. 16

represents the hybridizations of DP-107 and DP-178. It is important to keep in mind that the represented motifs, both parent and hybrid, are motif keys and not the depiction of the full-length motif needed to actually do the computer search.

Hybridizations can be performed on any combination of two or more motifs. Table 5 summarizes several three-motif hybridizations including GCN4, DP-107 (both frames), and DP-178 (also both frames). Notice that the resulting motifs are now becoming much more similar to each other. In fact, the first and third hybrid motifs are actually subsets of the second and fourth hybrid motifs respectively. This means that the first and third hybrid motifs are slightly more stringent than the second and fourth. It should also be noted that with only minor changes in these four motifs, or by hybridizing them, a single motif could be obtained which would find all of the sequences. However, it should be remembered that stringency is also reduced. Finally, the most broad-spectra and least-stringent hybrid motif is described in

FIG. 18

which summarizes the hybridization of GCN4, DP-107 (both frames), DP-178 (both frames), c-Fos, c-Jun, c-Myc, and Flu loop 36.

A special set of motifs was designed based on the fact that DP-178 is located only approximately ten amino acids upstream of the transmembrane spanning region of gp41 and just C-terminal to a proline which separates DP-107 and DP-178. It has postulated that DP-178 may be an amphipathic helix when membrane associated, and that the proline might aid in the initiation of the helix formation. The same arrangement was observed in Respiratory Syncytial Virus; however, the DP-178-like region in this virus also had a leucine zipper just C-terminal to the proline. Therefore, designed N-terminal proline-leucine zipper motifs were designed to analyze whether any other viruses might contain this same pattern. The motifs are summarized in FIG.

19

.

The PC/Gene protein database contains 5879 viral amino acid sequences (library file PVIRUSES; CD-ROM release 11.0). Of these, 1092 are viral envelope or glycoprotein sequences (library file PVIRUSE1). Tables V through X contain lists of protein sequence names and motif hit locations for all the motifs searched.

10. EXAMPLE

Computer-assisted Identification of DP-107 and DP-178-like Sequences in Human Immunodeficiency Virus

FIG. 20

represents search results for HIV-1 BRU isolate gp41 (PC/Gene protein sequence PENV_HV1BR). Notice that the hybrid motif which crosses DP-107 and DP-178 (named 107×178×4; the same motif as found in

FIG. 16

found three hits including amino acids 550-599, 636-688, and 796-823. These areas include DP-107 plus eight N-terminal and four C-terminal amino acids; DP-178 plus seven N-terminal and ten C-terminal amino acids; and an area inside the transmembrane region (cytoplasmic).

FIG. 20

(SEQ ID:26) also contains the results obtained from searching with the motif named ALLMOTI5, for which the key is found in

FIG. 17

({CDGHP} {CFP}×5). This motif also found three hits including DP-107 (amino acids 510-599), DP-178 (615-717), and a cytoplasmic region (772-841). These hits overlap the hits found by the motif 107×178×4 with considerable additional sequences on both the amino and carboxy termini. This is not surprising in that 107×178×4 is a subset of the ALLMOTI5 hybrid motif. Importantly, even though the stringency of ALLMOTI5 is considerably less than 107×178×4, it still selectively identifies the DP-107 and DP-178 regions of gp41 shown to contain sequences for inhibitory peptides of HIV-1. The results of these two motif searches are summarized in Table V under the PC/Gene protein sequence name PENV HV1BR. The proline-leucine zipper motifs also gave several hits in HIV-1 BRU including 503-525 which is at the very C-terminus of gp120, just upstream of the cleavage site (P7LZIPC and P12LZIPC); and 735-768 in the cytoplasmic domain of gp41 (P23LZIPC). These results are found in Tables VIII, IX, and X under the same sequence name as mentioned above. Notice that the only area of HIV-1 BRU which is predicted by the Lupas algorithm to contain a coiled-coil region, is from amino acids 635-670. This begins eight amino acids N-terminal to the start and ends eight amino acids N-terminal to the end of DP-178. DP-107, despite the fact that it is a known coiled coil, is not predicted to contain a coiled-coil region using the Lupas method.

11. EXAMPLE

Computer-assisted Identification of DP-107-like and DP-178-like Sequences in Human Respiratory Syncytial Virus

FIG. 21

represents search results (SEQ ID:27) for Human Respiratory Syncytial Virus (RSV; Strain A2) fusion glycoprotein F1 (PC/Gene protein sequence name PVGLF_HRSVA). Motif 107×178×4 finds three hits including amino acids 152-202, 213-243, and 488-515. The arrangement of these hits is similar to what is found in HIV-1 except that the motif finds two regions with similarities to DP-178, one just downstream of what would be called the DP-107 region or amino acids 213-243, and one just upstream of the transmembrane region (also similar to DP-178) or amino acids 488-515. Motif ALLMOTI5 also finds three areas including amino acids 116-202, 267-302, and 506-549. The proline-leucine zipper motifs also gave several hits including amino acids 205-221 and 265-287 (P1LZIPC 265-280, P12LZIPC), and 484-513 (P7LZIPC and P12LZIPC 484-506, P23LZIPC). Notice that the PLZIP motifs also identify regions which share location similarities with DP-178 of HIV-1.

12. EXAMPLE

Computer-assisted Identification of DP-107-like and DP-178-like Sequences in Simian Immunodeficiency Virus

Motif hits (SEQ ID:28) for Simian immunodeficiency Virus gp41 (AGM3 isolate; PC/Gene protein sequence name PENV_SIVAG) are shown in FIG.

22

. Motif 107×178×4 finds three hits including amino acids 566-593, 597-624, and 703-730. The first two hits only have three amino acids between them and could probably be combined into one hit from 566-624 which would represent a DP-107-like hit. Amino acids 703 to 730 would then represent a DP-178-like hit. ALLMOTI5 also finds three hits including amino acids 556-628 (DP-107-like), 651-699 (DP-178-like), and 808-852 which represents the transmembrane spanning region. SIV also has one region from 655-692 with a high propensity to form a coiled coil as predicted by the Lupas algorithm. Both 107×178×4 and ALLMOTI5 motifs find the same region. SIV does not have any PLZIP motif hits in gp41.

13. EXAMPLE

Computer-assisted Identification of DP-107-like and DP-178 Like Sequences in Canine Distemper Virus

Canine Distemper Virus (strain Onderstepoort) fusion glycoprotein F1 (PC/Gene Protein sequence name PVGLF_CDVO) has regions similar to Human RSV which are predicted to be DP-107-like and DP-178-like (

FIG. 23

, SEQ ID:29). Motif 107×178×4 highlights one area just C-terminal to the fusion peptide at amino acids 252-293. Amino acids 252-286 are also predicted to be coiled coil using the Lupas algorithm. Almost 100 amino acids C-terminal to the first region is a DP-178-like area at residues 340-367. ALLMOTI5 highlights three areas of interest including: amino acids 228-297, which completely overlaps both the Lupas prediction and the DP-107-like 107×178×4 hit; residues 340-381, which overlaps the second 107×178×4 hit; and amino acids 568-602, which is DP178-like in that it is located just N-terminal to the transmembrane region. It also overlaps another region (residues 570-602) predicted by the Lupas method to have a high propensity to form a coiled coil. Several PLZIP motifs successfully identified areas of interest including P6 and P12LZIPC which highlight residues 336-357 and 336-361 respectively; P1 and P12LZIPC which find residues 398-414; and P12 and P23LZIPC which find residues 562-589 and 562-592 respectively.

14. EXAMPLE

Computer-assisted Identification of DP-107-like and DP-178-like Sequences in Newcastle Disease Virus

FIG. 24

shows the motif hits (SEQ ID NO:30) found in Newcastle Disease Virus (strain Australia-Victoria/32; PC Gene protein sequence name PVGLF_NDVA). Motif 107×178×4 finds two areas including a DP-107-like hit at amino acids 151-178 and a DP-178-like hit at residues 426-512. ALLMOTI5 finds three areas including residues 117-182, 231-272, and 426-512. The hits from 426-512 include a region which is predicted by the Lupas method to have a high coiled-coil propensity (460-503). The PLZIP motifs identify only one region of interest at amino acids 273-289 (P1 and 12LZIPC).

15. EXAMPLE

Computer-assisted Identification of DP-107-like and DP-178-like Sequences in Human Parainfluenza Virus

Both motifs 107×178×4 and ALLMOTI5 exhibit DP-107-like hits in the same region, 115-182 and 117-182 respectively, of Human Parainfluenza Virus (strain NIH 47885; PC/Gene protein sequence name PVGLF_p13H4; (

FIG. 25

, SEQ ID NO:31). In addition, the two motifs have a DP-178-like hit just slightly C-terminal at amino acids 207-241. Both motifs also have DP-178-like hits nearer the transmembrane region including amino acids 457-497 and 462-512 respectively. Several PLZIP motif hits are also observed including 283-303 (P5LZIPC), 283-310 (P12LZIPC), 453-474 (P6LZIPC), and 453-481 (P23LZIPC). The Lupas algorithm predicts that amino acids 122-176 have a propensity to form a coiled-coil.

16. EXAMPLE

Computer-assisted Identification of DP-107-like and DP-178-like Sequences of Influenza A Virus

FIG. 26

illustrates the Lupas prediction (SEQ ID NO:32) for a coiled coil in Influenza A Virus (strain A/Aichi/2/68) at residues 379-436, as well as the motif hits for 107×178×4 at amino acids 387-453, and for ALLMOTI5 at residues 380-456. Residues 383-471 (38-125 of HA2) were shown by Carr and Kim to be an extended coiled coil when under acidic pH (Carr and Kim, 1993, Cell 73: 823-832). The Lupas algorithyan predicts a coiled-coil at residues 379-436. All three methods successfully predicted the region shown to actually have coiled-coil structure; however, ALLMOTI5 predicted the greatest portion of the 88 residue stretch.

17. EXAMPLE

RSV Antiviral Compounds

In the Example presented herein, respiratory syncytial virus (RSV) peptide sequences identified by utilizing the computer-assisted coiled-coil peptide sequence searches described in Example 9, above, are shown to encode peptide domains that exhibit structural similarity to actual, known coiled-coil peptides, and are, additionally found to exhibit antiviral activity.

17.1 Materials and Methods

Structural analyses consisted of circular dichroism (CD) studies, which were conducted according to the methods described in the Applicants' co-pending U.S. patent application Ser. No 08/073,028.

Anti-RSV antiviral activity was assayed as described in Pringle, C. R. et al., 1985, J. Medical Vir. 17:377-386.

A 48 amino acid RSV F2 peptide (SEQ ID NO:33) and a 53 amino acid F1-178 (SEQ ID NO:34) peptide are utilized which span sequences that were identified via the computer assisted peptide sequence search strategies described in Example 9, above. See

FIG. 21

for the exact position of these sequences and for the motifs utilized.

17.2 Results

35-mer oligopeptides were synthesized which constituted portions of the 48 amino acid RSV F2 peptide sequence (

FIG. 27

) and portions of the 53 amino acid F1-178 peptide sequence (FIG.

28

). The oligopeptides were assayed, via CD analysis, for structural similarity to known coiled-coil structures, and for anti-RSV activity. As shown in

FIGS. 27 and 28

, a number of these oligopeptides exhibited substantial coiled-coil structural similarity and/or antiviral activity.

Thus, the computer assisted searches described, herein, in Example 9, for example, successfully identified viral peptide domains that represent highly promising anti-RSV antiviral compounds.

18. EXAMPLE

HPF3 Antiviral Compounds

In the Example presented herein, human parainfluenza virus 3 (HPF3) peptide sequences identified by utilizing the computer-assisted coiled-coil peptide sequence searches described in Example 9, above, are shown to encode peptide domains that exhibit structural similarity to actual, known coiled-coil peptides, and are, additionally found to exhibit antiviral activity.

18.1 Materials and Methods

Structural analyses consisted of circular dichroism (CD) studies, which were conducted according to the methods described in the Applicants' co-pending U.S. patent application Ser. No 08/073,028.

Anti-HPF3 antiviral activity was assayed as described in Pringle, C. R. et al., 1985, J. Medical Vir. 17:377-386.

A 56 amino acid and 70 amino acid HPF3 peptide are utilized which span sequences that were identified via the computer assisted peptide sequence search strategies described in Example 9, above. See

FIG. 25

for the exact positions of these sequences and for the motifs utilized.

18.2 Results

35-mer oligopeptides were synthesized which constituted portions of the 56 amino acid (SEQ ID NO:35) sequence (

FIG. 29

) and portions of the 70 amino acid HPF3 peptide (SEQ ID NO:36) sequence (FIG.

30

). The oligopeptides were assayed, via CD analysis, for structural similarity to known coiled-coil structures, and for anti-HPF3 activity. As shown in

FIGS. 29 and 30

, a number of these oligopeptides exhibited substantial coiled-coil structural similarity and/or antiviral activity.

Thus, the computer assisted searches described, herein, in Example 9, for example, successfully identified viral peptide domains that represent highly promising anti-HPF3 antiviral compounds.

The present invention is not to be limited in scope by the specific embodiments described which are intended as single illustrations of individual aspects of the invention, and functionally equivalent methods and components are within the scope of the invention. Indeed, various modifications of the invention, in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications are intended to fall within the scope of the appended claims.

111

36 amino acids

amino acid

unknown

peptide

1
Tyr Thr Ser Leu Ile His Ser Leu Ile Glu Glu Ser Gln Asn Gln Gln
1 5 10 15
Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu
20 25 30
Trp Asn Trp Phe
35

36 amino acids

amino acid

unknown

peptide

2
Ser Ser Glu Ser Phe Thr Leu Leu Glu Gln Trp Asn Asn Trp Lys Leu
1 5 10 15
Gln Leu Ala Glu Gln Trp Leu Glu Gln Ile Asn Glu Lys His Tyr Leu
20 25 30
Glu Asp Ile Ser
35

36 amino acids

amino acid

unknown

peptide

3
Tyr Thr Asn Thr Ile Tyr Thr Leu Leu Glu Glu Ser Gln Asn Gln Gln
1 5 10 15
Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu
20 25 30
Trp Asn Trp Phe
35

36 amino acids

amino acid

unknown

peptide

4
Tyr Thr Gly Ile Ile Tyr Asn Leu Leu Glu Glu Ser Gln Asn Gln Gln
1 5 10 15
Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Asn Leu
20 25 30
Trp Asn Trp Phe
35

36 amino acids

amino acid

unknown

peptide

5
Tyr Thr Ser Leu Ile Tyr Ser Leu Leu Glu Lys Ser Gln Thr Gln Gln
1 5 10 15
Glu Lys Asn Glu Gln Glu Leu Leu Glu Leu Asp Lys Trp Ala Ser Leu
20 25 30
Trp Asn Trp Phe
35

36 amino acids

amino acid

unknown

peptide

6
Leu Glu Ala Asn Ile Ser Lys Ser Leu Glu Gln Ala Gln Ile Gln Gln
1 5 10 15
Glu Lys Asn Met Tyr Glu Leu Gln Lys Leu Asn Ser Trp Asp Ile Phe
20 25 30
Gly Asn Trp Phe
35

36 amino acids

amino acid

unknown

peptide

7
Leu Glu Ala Asn Ile Ser Gln Ser Leu Glu Gln Ala Gln Ile Gln Gln
1 5 10 15
Glu Lys Asn Met Tyr Glu Leu Gln Lys Leu Asn Ser Trp Asp Val Phe
20 25 30
Thr Asn Trp Leu
35

41 amino acids

amino acid

unknown

peptide

8
Cys Gly Gly Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu
1 5 10 15
Leu Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu
20 25 30
Ala Val Glu Arg Tyr Leu Lys Asp Gln
35 40

17 amino acids

amino acid

unknown

peptide

9
Leu Gln Ala Arg Ile Leu Ala Val Glu Arg Tyr Leu Lys Asp Gln Gln
1 5 10 15
Gln

38 amino acids

amino acid

unknown

peptide

10
Gln Gln Leu Leu Asp Val Val Lys Arg Gln Gln Glu Met Leu Arg Leu
1 5 10 15
Thr Val Trp Gly Thr Lys Asn Leu Gln Ala Arg Val Thr Ala Ile Glu
20 25 30
Lys Tyr Leu Lys Asp Gln
35

21 base pairs

nucleic acid

single

linear

DNA (genomic)

11
ATGACGCTGA CGGTACAGGC C 21

33 base pairs

nucleic acid

single

linear

DNA (genomic)

12
TGACTAAGCT TAATACCACA GCCAATTTGT TAT 33

22 base pairs

nucleic acid

single

linear

DNA (genomic)

13
GGAGCTGCTT GGGGCCCCAG AC 22

40 base pairs

nucleic acid

single

linear

DNA (genomic)

14
CCAAATCCCC AGGAGCTGCT CGAGCTGCAC TATACCAGAC 40

35 base pairs

nucleic acid

single

linear

DNA (genomic)

15
ATAGCTTCTA GATTAATTGT TAATTTCTCT GTCCC 35

50 amino acids

amino acid

unknown

peptide

Peptide

/label= A
/note= “x comprises an amino group, an acetyl
group, a 9-fluoromethyoxymethyl-carbonyl group, a
hydrophobic group, or a macromolecule carrier

Peptide

/label= B
/note= ” x comprises a carboxyl group, an amido
group, a hydrophobic group, or a macromolecular
carrier group.“

16
Xaa Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile Lys Glu Asn
1 5 10 15
Lys Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys Gln Glu Leu
20 25 30
Asp Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu Met Gln Ser
35 40 45
Thr Xaa
50

39 amino acids

amino acid

unknown

peptide

Peptide

/label= A
/note= ”x comprises an amino group, an acetyl
group, a 9-fluoromethyoxymethyl-carbonyl group, or
a macromolecule carrier group.“

Peptide

/label= B
/note= ”x comprises a carboxyl group, an amido
group, a hydrophobic group, or a macromolecular
carrier group.“

17
Xaa Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser
1 5 10 15
Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg
20 25 30
Lys Ser Asp Glu Leu Leu Xaa
35

37 amino acids

amino acid

unknown

peptide

Peptide

/label= A
/note= ”x comprises an amino group, an acetly
group, a 9-fluoromethyoxymethyl-carbonyl group, a
hydrophobic group, or a macromolecule carrier

Peptide

/label= B
/note= “x comprises a carboxyl group, an amido
group, a hydrophobic group, or a macromolecular
carrier group.”

18
Xaa Ile Thr Leu Asn Asn Ser Val Ala Leu Asp Pro Ile Asp Ile Ser
1 5 10 15
Ile Glu Leu Asn Lys Ala Lys Ser Asp Leu Glu Glu Ser Lys Glu Trp
20 25 30
Ile Arg Arg Ser Xaa
35

37 amino acids

amino acid

unknown

peptide

Peptide

/label= A
/note= “x comprises an amino group, an acetly
group, a 9-fluoromethyoxymethyl-carbonyl group, a
hydrophobic group, or a macromolecule carrier

Peptide

/label= B
/note= ”x comprises a carboxyl group, an amido
group, a hydrophobic group, or a macromolecular
carrier group.“

19
Xaa Ala Leu Gly Val Ala Thr Ser Ala Gln Ile Thr Ala Ala Val Ala
1 5 10 15
Leu Val Glu Ala Lys Gln Ala Arg Ser Asp Ile Glu Lys Leu Lys Glu
20 25 30
Ala Ile Arg Asp Xaa
35

28 amino acids

amino acid

unknown

peptide

20
Met Lys Gln Leu Glu Asp Lys Val Glu Glu Leu Leu Ser Lys Asn Tyr
1 5 10 15
His Leu Glu Asn Glu Val Ala Arg Leu Lys Lys Leu
20 25

28 amino acids

amino acid

unknown

peptide

21
Thr Asp Thr Leu Gln Ala Glu Thr Asp Gln Leu Glu Asp Glu Lys Ser
1 5 10 15
Ala Leu Gln Thr Glu Ile Ala Asn Leu Leu Lys Glu
20 25

28 amino acids

amino acid

unknown

peptide

22
Ile Ala Arg Leu Glu Glu Lys Val Lys Thr Leu Lys Ala Gln Asn Ser
1 5 10 15
Glu Leu Ala Ser Thr Ala Asn Met Leu Arg Glu Gln
20 25

28 amino acids

amino acid

unknown

peptide

23
Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Leu Glu Lys Arg Arg Glu
1 5 10 15
Gln Leu Lys His Lys Leu Glu Gln Leu Arg Asn Ser
20 25

28 amino acids

amino acid

unknown

peptide

24
Ile Glu Lys Thr Asn Glu Lys Phe His Gln Ile Glu Lys Glu Phe Ser
1 5 10 15
Glu Val Glu Gly Arg Ile Gln Asp Leu Glu Lys Tyr
20 25

38 amino acids

amino acid

unknown

peptide

25
Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu Gln Leu
1 5 10 15
Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala Val Glu
20 25 30
Arg Tyr Leu Lys Asp Gln
35

338 amino acids

amino acid

unknown

protein

26
Phe Leu Gly Phe Leu Gly Ala Ala Gly Ser Thr Met Gly Ala Arg Ser
1 5 10 15
Met Thr Leu Thr Val Gln Ala Arg Gln Leu Leu Ser Gly Ile Val Gln
20 25 30
Gln Gln Asn Asn Leu Leu Arg Ala Ile Glu Ala Gln Gln His Leu Leu
35 40 45
Gln Leu Thr Val Trp Gly Ile Lys Gln Leu Gln Ala Arg Ile Leu Ala
50 55 60
Val Glu Arg Tyr Leu Lys Asp Gln Gln Leu Leu Gly Ile Trp Gly Cys
65 70 75 80
Ser Gly Lys Leu Ile Cys Thr Thr Ala Val Pro Trp Asn Ala Ser Trp
85 90 95
Ser Asn Lys Ser Leu Glu Gln Ile Trp Asn Asn Met Thr Trp Met Glu
100 105 110
Trp Asp Arg Glu Ile Asn Asn Tyr Thr Ser Leu Ile His Ser Leu Ile
115 120 125
Glu Glu Ser Gln Asn Gln Gln Glu Lys Asn Glu Gln Glu Leu Leu Glu
130 135 140
Leu Asp Lys Trp Ala Ser Leu Trp Asn Trp Phe Asn Ile Thr Asn Trp
145 150 155 160
Leu Trp Tyr Ile Lys Ile Phe Ile Met Ile Val Gly Gly Leu Val Gly
165 170 175
Leu Arg Ile Val Phe Ala Val Leu Ser Ile Val Asn Arg Val Arg Gln
180 185 190
Gly Tyr Ser Pro Leu Ser Phe Gln Thr His Leu Pro Thr Pro Arg Gly
195 200 205
Pro Asp Arg Pro Glu Gly Ile Glu Glu Glu Gly Gly Glu Arg Asp Arg
210 215 220
Asp Arg Ser Ile Arg Leu Val Asn Gly Ser Leu Ala Leu Ile Trp Asp
225 230 235 240
Asp Leu Arg Ser Leu Cys Leu Phe Ser Tyr His Arg Leu Arg Asp Leu
245 250 255
Leu Leu Ile Val Thr Arg Ile Val Glu Leu Leu Gly Arg Arg Gly Trp
260 265 270
Glu Ala Leu Lys Tyr Trp Trp Asn Leu Leu Gln Tyr Trp Ser Gln Glu
275 280 285
Leu Lys Asn Ser Ala Val Ser Leu Leu Asn Ala Thr Ala Ile Ala Val
290 295 300
Ala Glu Gly Thr Asp Arg Val Ile Glu Val Val Gln Gly Ala Cys Arg
305 310 315 320
Ala Ile Arg His Ile Pro Arg Arg Ile Arg Gln Gly Leu Glu Arg Ile
325 330 335
Leu Leu

437 amino acids

amino acid

unknown

protein

27
Phe Leu Gly Phe Leu Leu Gly Val Gly Ser Ala Ile Ala Ser Gly Val
1 5 10 15
Ala Val Ser Lys Val Leu His Leu Glu Gly Glu Val Asn Lys Ile Lys
20 25 30
Ser Ala Leu Leu Ser Thr Asn Lys Ala Val Val Ser Leu Ser Asn Gly
35 40 45
Val Ser Val Leu Thr Ser Lys Val Leu Asp Leu Lys Asn Tyr Ile Asp
50 55 60
Lys Gln Leu Leu Pro Ile Val Asn Lys Gln Ser Cys Ser Ile Ser Asn
65 70 75 80
Ile Glu Thr Val Ile Glu Phe Gln Gln Lys Asn Asn Arg Leu Leu Glu
85 90 95
Ile Thr Arg Glu Phe Ser Val Asn Ala Gly Val Thr Thr Pro Val Ser
100 105 110
Thr Met Leu Thr Asn Ser Glu Leu Leu Ser Leu Ile Asn Asp Met Pro
115 120 125
Ile Thr Asn Asp Gln Lys Lys Leu Met Ser Asn Asn Val Gln Ile Val
130 135 140
Arg Gln Gln Ser Tyr Ser Ile Met Ser Ile Ile Lys Glu Glu Val Leu
145 150 155 160
Ala Tyr Val Val Gln Leu Pro Leu Tyr Gly Val Ile Asp Thr Pro Cys
165 170 175
Trp Lys Leu His Thr Ser Pro Leu Cys Thr Thr Asn Thr Lys Glu Gly
180 185 190
Ser Asn Ile Cys Leu Thr Arg Thr Asp Arg Gly Trp Tyr Cys Asp Asn
195 200 205
Ala Gly Ser Val Ser Phe Phe Pro Gln Ala Glu Thr Cys Lys Val Gln
210 215 220
Ser Asn Arg Val Phe Cys Asp Thr Met Asn Ser Leu Thr Leu Pro Ser
225 230 235 240
Glu Ile Asn Leu Cys Asn Val Asp Ile Phe Asn Pro Lys Tyr Asp Cys
245 250 255
Lys Ile Met Thr Ser Lys Thr Asp Val Ser Ser Ser Val Ile Thr Ser
260 265 270
Leu Gly Ala Ile Val Ser Cys Tyr Gly Lys Thr Lys Cys Thr Ala Ser
275 280 285
Asn Lys Asn Arg Gly Ile Ile Lys Thr Phe Ser Asn Gly Cys Asp Tyr
290 295 300
Val Ser Asn Lys Gly Met Asp Thr Val Ser Val Gly Asn Thr Leu Tyr
305 310 315 320
Tyr Val Asn Lys Gln Glu Gly Lys Ser Leu Tyr Val Lys Gly Glu Pro
325 330 335
Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp
340 345 350
Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe
355 360 365
Ile Arg Lys Ser Asp Glu Leu Leu His Asn Val Asn Ala Gly Lys Ser
370 375 380
Thr Thr Asn Ile Met Ile Thr Thr Ile Ile Ile Val Ile Ile Val Ile
385 390 395 400
Leu Leu Ser Leu Ile Ala Val Gly Leu Leu Leu Tyr Cys Lys Ala Arg
405 410 415
Ser Thr Pro Val Thr Leu Ser Lys Asp Gln Leu Ser Gly Ile Asn Asn
420 425 430
Ile Ala Phe Ser Asn
435

328 amino acids

amino acid

unknown

protein

28
Phe Leu Gly Phe Leu Gly Ala Ala Gly Thr Ala Met Gly Ala Ala Ala
1 5 10 15
Thr Ala Leu Thr Val Gln Ser Gln His Leu Leu Ala Gly Ile Leu Gln
20 25 30
Gln Gln Lys Asn Leu Leu Ala Ala Val Glu Ala Gln Gln Gln Met Leu
35 40 45
Lys Leu Thr Ile Trp Gly Val Lys Asn Leu Asn Ala Arg Val Thr Ala
50 55 60
Leu Glu Lys Tyr Leu Glu Asp Gln Ala Arg Leu Asn Ala Trp Gly Cys
65 70 75 80
Ala Trp Lys Gln Val Cys His Thr Thr Val Pro Trp Gln Trp Asn Asn
85 90 95
Arg Thr Pro Asp Trp Asn Asn Met Thr Trp Leu Glu Trp Glu Arg Gln
100 105 110
Ile Ser Tyr Leu Glu Gly Asn Ile Thr Thr Gln Leu Glu Glu Ala Arg
115 120 125
Ala Gln Glu Glu Lys Asn Leu Asp Ala Tyr Gln Lys Leu Ser Ser Trp
130 135 140
Ser Asp Phe Trp Ser Trp Phe Asp Phe Ser Lys Trp Leu Asn Ile Leu
145 150 155 160
Lys Ile Gly Phe Leu Asp Val Leu Gly Ile Ile Gly Leu Arg Leu Leu
165 170 175
Tyr Thr Val Tyr Ser Cys Ile Ala Arg Val Arg Gln Gly Tyr Ser Pro
180 185 190
Leu Ser Pro Gln Ile His Ile His Pro Trp Lys Gly Gln Pro Asp Asn
195 200 205
Ala Glu Gly Pro Gly Glu Gly Gly Asp Lys Arg Lys Asn Ser Ser Glu
210 215 220
Pro Trp Gln Lys Glu Ser Gly Thr Ala Glu Trp Lys Ser Asn Trp Cys
225 230 235 240
Lys Arg Leu Thr Asn Trp Cys Ser Ile Ser Ser Ile Trp Leu Tyr Asn
245 250 255
Ser Cys Leu Thr Leu Leu Val His Leu Arg Ser Ala Phe Gln Tyr Ile
260 265 270
Gln Tyr Gly Leu Gly Glu Leu Lys Ala Ala Ala Gln Glu Ala Val Val
275 280 285
Ala Leu Ala Arg Leu Ala Gln Asn Ala Gly Tyr Gln Ile Trp Leu Ala
290 295 300
Cys Arg Ser Ala Tyr Arg Ala Ile Ile Asn Ser Pro Arg Arg Val Arg
305 310 315 320
Gln Gly Leu Glu Gly Ile Leu Asn
325

438 amino acids

amino acid

unknown

protein

29
Phe Ala Gly Val Val Leu Ala Gly Val Ala Leu Gly Val Ala Thr Ala
1 5 10 15
Ala Gln Ile Thr Ala Gly Ile Ala Leu His Gln Ser Asn Leu Asn Ala
20 25 30
Gln Ala Ile Gln Ser Leu Arg Thr Ser Leu Glu Gln Ser Asn Lys Ala
35 40 45
Ile Glu Glu Ile Arg Glu Ala Thr Gln Glu Thr Val Ile Ala Val Gln
50 55 60
Gly Val Gln Asp Tyr Val Asn Asn Glu Leu Val Pro Ala Met Gln His
65 70 75 80
Met Ser Cys Glu Leu Val Gly Gln Arg Leu Gly Leu Arg Leu Leu Arg
85 90 95
Tyr Tyr Thr Glu Leu Leu Ser Ile Phe Gly Pro Ser Leu Arg Asp Pro
100 105 110
Ile Ser Ala Glu Ile Ser Ile Gln Ala Leu Ile Tyr Ala Leu Gly Gly
115 120 125
Glu Ile His Lys Ile Leu Glu Lys Leu Gly Tyr Ser Gly Ser Asp Met
130 135 140
Ile Ala Ile Leu Glu Ser Arg Gly Ile Lys Thr Lys Ile Thr His Val
145 150 155 160
Asp Leu Pro Gly Lys Phe Ile Ile Leu Ser Ile Ser Tyr Pro Thr Leu
165 170 175
Ser Glu Val Lys Gly Val Ile Val His Arg Leu Glu Ala Val Ser Tyr
180 185 190
Asn Ile Gly Ser Gln Glu Trp Tyr Thr Thr Val Pro Arg Tyr Ile Ala
195 200 205
Thr Asn Gly Tyr Leu Ile Ser Asn Phe Asp Glu Ser Ser Cys Val Phe
210 215 220
Val Ser Glu Ser Ala Ile Cys Ser Gln Asn Ser Leu Tyr Pro Met Ser
225 230 235 240
Pro Leu Leu Gln Gln Cys Ile Arg Gly Asp Thr Ser Ser Cys Ala Arg
245 250 255
Thr Leu Val Ser Gly Thr Met Gly Asn Lys Phe Ile Leu Ser Lys Gly
260 265 270
Asn Ile Val Ala Asn Cys Ala Ser Ile Leu Cys Lys Cys Tyr Ser Thr
275 280 285
Ser Thr Ile Ile Asn Gln Ser Pro Asp Lys Leu Leu Thr Phe Ile Ala
290 295 300
Ser Asp Thr Cys Pro Leu Val Glu Ile Asp Gly Ala Thr Ile Gln Val
305 310 315 320
Gly Gly Arg Gln Tyr Pro Asp Met Val Tyr Glu Gly Lys Val Ala Leu
325 330 335
Gly Pro Ala Ile Ser Leu Asp Arg Leu Asp Val Gly Thr Asn Leu Gly
340 345 350
Asn Ala Leu Lys Lys Leu Asp Asp Ala Lys Val Leu Ile Asp Ser Ser
355 360 365
Asn Gln Ile Leu Glu Thr Val Arg Arg Ser Ser Phe Asn Phe Gly Ser
370 375 380
Leu Leu Ser Val Pro Ile Leu Ser Cys Thr Ala Leu Ala Leu Leu Leu
385 390 395 400
Leu Ile Tyr Cys Cys Lys Arg Arg Tyr Gln Gln Thr Leu Lys Gln His
405 410 415
Thr Lys Val Asp Pro Ala Phe Lys Pro Asp Leu Thr Gly Thr Ser Lys
420 425 430
Ser Tyr Val Arg Ser Leu
435

436 amino acids

amino acid

unknown

protein

30
Phe Ile Gly Ala Ile Ile Gly Ser Val Ala Leu Gly Val Ala Thr Ala
1 5 10 15
Ala Gln Ile Thr Ala Ala Ser Ala Leu Ile Gln Ala Asn Gln Asn Ala
20 25 30
Ala Asn Ile Leu Arg Leu Lys Glu Ser Ile Thr Ala Thr Ile Glu Ala
35 40 45
Val His Glu Val Thr Asp Gly Leu Ser Gln Leu Ala Val Ala Val Gly
50 55 60
Lys Met Gln Gln Phe Val Asn Asp Gln Phe Asn Asn Thr Ala Gln Glu
65 70 75 80
Leu Asp Cys Ile Lys Ile Thr Gln Gln Val Gly Val Glu Leu Asn Leu
85 90 95
Tyr Leu Thr Glu Leu Thr Thr Val Phe Gly Pro Gln Ile Thr Ser Pro
100 105 110
Ala Leu Thr Gln Leu Thr Ile Gln Ala Leu Tyr Asn Ala Gly Gly Asn
115 120 125
Met Asp Tyr Leu Leu Thr Lys Leu Gly Val Gly Asn Asn Gln Leu Ser
130 135 140
Ser Leu Ile Gly Ser Gly Leu Ile Thr Gly Asn Pro Ile Leu Tyr Asp
145 150 155 160
Ser Gln Thr Gln Leu Leu Gly Ile Gln Val Thr Leu Pro Ser Val Gly
165 170 175
Asn Leu Asn Asn Met Arg Ala Thr Tyr Leu Glu Thr Leu Ser Val Ser
180 185 190
Thr Thr Lys Gly Phe Ala Ser Ala Leu Val Pro Lys Val Val Thr Gln
195 200 205
Val Gly Ser Val Ile Glu Glu Leu Asp Thr Ser Tyr Cys Ile Glu Thr
210 215 220
Asp Leu Asp Leu Tyr Cys Thr Arg Ile Val Thr Phe Pro Met Ser Pro
225 230 235 240
Gly Ile Tyr Ser Cys Leu Asn Gly Asn Thr Ser Ala Cys Met Tyr Ser
245 250 255
Lys Thr Glu Gly Ala Leu Thr Thr Pro Tyr Met Thr Leu Lys Gly Ser
260 265 270
Val Ile Ala Asn Cys Lys Met Thr Thr Cys Arg Cys Ala Asp Pro Pro
275 280 285
Gly Ile Ile Ser Gln Asn Tyr Gly Glu Ala Val Ser Leu Ile Asp Arg
290 295 300
His Ser Cys Asn Val Leu Ser Leu Asp Gly Ile Thr Leu Arg Leu Ser
305 310 315 320
Gly Glu Phe Asp Ala Thr Tyr Gln Lys Asn Ile Ser Ile Leu Asp Ser
325 330 335
Gln Val Ile Val Thr Gly Asn Leu Asp Ile Ser Thr Glu Leu Gly Asn
340 345 350
Val Asn Asn Ser Ile Ser Asn Ala Leu Asp Lys Leu Glu Glu Ser Asn
355 360 365
Ser Lys Leu Asp Lys Val Asn Val Lys Leu Thr Ser Thr Ser Ala Leu
370 375 380
Ile Thr Tyr Ile Ala Leu Thr Ala Ile Ser Leu Val Cys Gly Ile Leu
385 390 395 400
Ser Leu Val Leu Ala Cys Tyr Leu Met Tyr Lys Gln Lys Ala Gln Gln
405 410 415
Lys Thr Leu Leu Trp Leu Gly Asn Asn Thr Leu Gly Gln Met Arg Ala
420 425 430
Thr Thr Lys Met
435

430 amino acids

amino acid

unknown

protein

31
Phe Phe Gly Gly Val Ile Gly Thr Ile Ala Leu Gly Val Ala Thr Ser
1 5 10 15
Ala Gln Ile Thr Ala Ala Val Ala Leu Val Glu Ala Lys Gln Ala Arg
20 25 30
Ser Asp Ile Glu Lys Leu Lys Glu Ala Ile Arg Asp Thr Asn Lys Ala
35 40 45
Val Gln Ser Val Gln Ser Ser Ile Gly Asn Leu Ile Val Ala Ile Lys
50 55 60
Ser Val Gln Asp Tyr Val Asn Lys Glu Ile Val Pro Ser Ile Ala Arg
65 70 75 80
Leu Gly Cys Glu Ala Ala Gly Leu Gln Leu Gly Ile Ala Leu Thr Gln
85 90 95
His Tyr Ser Glu Leu Thr Asn Ile Phe Gly Asp Asn Ile Gly Ser Leu
100 105 110
Gln Glu Lys Gly Ile Lys Leu Gln Gly Ile Ala Ser Leu Tyr Arg Thr
115 120 125
Asn Ile Thr Glu Ile Phe Thr Thr Ser Thr Val Asp Lys Tyr Asp Ile
130 135 140
Tyr Asp Leu Leu Phe Thr Glu Ser Ile Lys Val Arg Val Ile Asp Val
145 150 155 160
Asp Leu Asn Asp Tyr Ser Ile Thr Leu Gln Val Arg Leu Pro Leu Leu
165 170 175
Thr Arg Leu Leu Asn Thr Gln Ile Tyr Arg Val Asp Ser Ile Ser Tyr
180 185 190
Asn Ile Gln Asn Arg Glu Trp Tyr Ile Pro Leu Pro Ser His Ile Met
195 200 205
Thr Lys Gly Ala Phe Leu Gly Gly Ala Asp Val Lys Glu Cys Ile Glu
210 215 220
Ala Phe Ser Ser Tyr Ile Cys Pro Ser Asp Pro Gly Phe Val Leu Asn
225 230 235 240
His Glu Met Glu Ser Cys Leu Ser Gly Asn Ile Ser Gln Cys Pro Arg
245 250 255
Thr Val Val Lys Ser Asp Ile Val Pro Arg Tyr Ala Phe Val Asn Gly
260 265 270
Gly Val Val Ala Asn Cys Ile Thr Thr Thr Cys Thr Cys Asn Gly Ile
275 280 285
Gly Asn Arg Ile Asn Gln Pro Pro Asp Gln Gly Val Lys Ile Ile Thr
290 295 300
His Lys Glu Cys Asn Thr Ile Gly Ile Asn Gly Met Leu Phe Asn Thr
305 310 315 320
Asn Lys Glu Gly Thr Leu Ala Phe Tyr Thr Pro Asn Asp Ile Thr Leu
325 330 335
Asn Asn Ser Val Ala Leu Asp Pro Ile Asp Ile Ser Ile Glu Leu Asn
340 345 350
Lys Ala Lys Ser Asp Leu Glu Glu Ser Lys Glu Trp Ile Arg Arg Ser
355 360 365
Asn Gln Lys Leu Asp Ser Ile Gly Asn Trp His Gln Ser Ser Thr Thr
370 375 380
Ile Ile Ile Val Leu Ile Met Ile Ile Ile Leu Phe Ile Ile Asn Val
385 390 395 400
Thr Ile Ile Ile Ile Ala Val Lys Tyr Tyr Arg Ile Gln Lys Arg Asn
405 410 415
Arg Val Asp Gln Asn Asp Lys Pro Tyr Val Leu Thr Asn Lys
420 425 430

221 amino acids

amino acid

unknown

protein

32
Gly Leu Phe Gly Ala Ile Ala Gly Phe Ile Glu Asn Gly Trp Glu Gly
1 5 10 15
Met Ile Asp Gly Trp Tyr Gly Phe Arg His Gln Asn Ser Glu Gly Thr
20 25 30
Gly Gln Ala Ala Asp Leu Lys Ser Thr Gln Ala Ala Ile Asp Gln Ile
35 40 45
Asn Gly Lys Leu Asn Arg Val Ile Glu Lys Thr Asn Glu Lys Phe His
50 55 60
Gln Ile Glu Lys Glu Phe Ser Glu Val Glu Gly Arg Ile Gln Asp Leu
65 70 75 80
Glu Lys Tyr Val Glu Asp Thr Lys Ile Asp Leu Trp Ser Tyr Asn Ala
85 90 95
Glu Leu Leu Val Ala Leu Glu Asn Gln His Thr Ile Asp Leu Thr Asp
100 105 110
Ser Glu Met Asn Lys Leu Phe Glu Lys Thr Arg Arg Gln Leu Arg Glu
115 120 125
Asn Ala Glu Glu Met Gly Asn Gly Cys Phe Lys Ile Tyr His Lys Cys
130 135 140
Asp Asn Ala Cys Ile Glu Ser Ile Arg Asn Gly Thr Tyr Asp His Asp
145 150 155 160
Val Tyr Arg Asp Glu Ala Leu Asn Asn Arg Phe Gln Ile Lys Gly Val
165 170 175
Glu Leu Lys Ser Gly Tyr Lys Asp Trp Ile Leu Trp Ile Ser Phe Ala
180 185 190
Ile Ser Cys Phe Leu Leu Cys Val Val Leu Leu Gly Phe Ile Met Trp
195 200 205
Ala Cys Gln Arg Gly Asn Ile Arg Cys Asn Ile Cys Ile
210 215 220

48 amino acids

amino acid

unknown

peptide

33
Tyr Thr Ser Val Ile Thr Ile Glu Leu Ser Asn Ile Lys Glu Asn Lys
1 5 10 15
Cys Asn Gly Thr Asp Ala Lys Val Lys Leu Ile Lys Gln Glu Leu Asp
20 25 30
Lys Tyr Lys Asn Ala Val Thr Glu Leu Gln Leu Leu Met Gln Ser Thr
35 40 45

53 amino acids

amino acid

unknown

peptide

34
Gly Glu Pro Ile Ile Asn Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp
1 5 10 15
Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
20 25 30
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu His Asn Val Asn Ala
35 40 45
Gly Lys Ser Thr Thr
50

56 amino acids

amino acid

unknown

peptide

35
Tyr Thr Pro Asn Asp Ile Thr Leu Asn Asn Ser Val Ala Leu Asp Pro
1 5 10 15
Ile Asp Ile Ser Ile Glu Leu Asn Lys Ala Lys Ser Asp Leu Glu Glu
20 25 30
Ser Lys Glu Trp Ile Arg Arg Ser Asn Gln Lys Leu Asp Ser Ile Gly
35 40 45
Asn Trp His Gln Ser Ser Thr Thr
50 55

70 amino acids

amino acid

unknown

peptide

36
Gly Thr Ile Ala Leu Gly Val Ala Thr Ser Ala Gln Ile Thr Ala Ala
1 5 10 15
Val Ala Leu Val Glu Ala Lys Gln Ala Arg Ser Asp Ile Glu Lys Leu
20 25 30
Lys Glu Ala Ile Arg Asp Thr Asn Lys Ala Val Gln Ser Val Gln Ser
35 40 45
Ser Ile Gly Asn Leu Ile Val Ala Ile Lys Ser Val Gln Asp Tyr Val
50 55 60
Asn Lys Glu Ile Val Pro
65 70

4 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

37
Phe Tyr Asp Pro
1

5 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

38
Phe Tyr Asp Pro Leu
1 5

6 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

39
Phe Tyr Asp Pro Leu Val
1 5

7 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

40
Phe Tyr Asp Pro Leu Val Phe
1 5

8 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

41
Phe Tyr Asp Pro Leu Val Phe Pro
1 5

9 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

42
Phe Tyr Asp Pro Leu Val Phe Pro Ser
1 5

10 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

43
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp
1 5 10

11 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

44
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu
1 5 10

12 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

45
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe
1 5 10

13 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

46
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp
1 5 10

14 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

47
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala
1 5 10

15 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

48
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser
1 5 10 15

16 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

49
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15

17 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

50
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser

18 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

51
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln

19 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

52
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val

20 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

53
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn
20

21 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

54
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu
20

22 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

55
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys
20

23 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

56
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile
20

24 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

57
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn
20

25 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

58
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln
20 25

26 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

59
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
20 25

27 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

60
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
20 25

28 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

61
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala
20 25

29 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

62
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe
20 25

30 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

63
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile
20 25 30

31 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

64
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg
20 25 30

32 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic
group or a macromolecular carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

65
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys
20 25 30

33 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

66
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys
20 25 30
Ser

34 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

67
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys
20 25 30
Ser Asp

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

68
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys
20 25 30
Ser Asp Glu
35

36 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

69
Phe Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile
1 5 10 15
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys
20 25 30
Ser Asp Glu Leu
35

4 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

70
Asp Glu Leu Leu
1

5 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

71
Ser Asp Glu Leu Leu
1 5

6 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

72
Lys Ser Asp Glu Leu Leu
1 5

7 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

73
Arg Lys Ser Asp Glu Leu Leu
1 5

8 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

74
Ile Arg Lys Ser Asp Glu Leu Leu
1 5

9 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

75
Phe Ile Arg Lys Ser Asp Glu Leu Leu
1 5

10 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

76
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
1 5 10

11 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

77
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
1 5 10

12 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

78
Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
1 5 10

13 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

79
Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
1 5 10

14 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group, or
a macromolecular carrier group.“

80
Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
1 5 10

15 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

81
Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
1 5 10 15

16 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

82
Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
1 5 10 15

17 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

83
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
1 5 10 15
Leu

18 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

84
Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu
1 5 10 15
Leu Leu

19 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

85
Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp
1 5 10 15
Glu Leu Leu

20 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

86
Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser
1 5 10 15
Asp Glu Leu Leu
20

21 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

87
Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys
1 5 10 15
Ser Asp Glu Leu Leu
20

22 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

88
Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg
1 5 10 15
Lys Ser Asp Glu Leu Leu
20

23 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

89
Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile
1 5 10 15
Arg Lys Ser Asp Glu Leu Leu
20

24 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

90
Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe
1 5 10 15
Ile Arg Lys Ser Asp Glu Leu Leu
20

25 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

91
Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala
1 5 10 15
Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25

26 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

92
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
1 5 10 15
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25

27 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

93
Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser
1 5 10 15
Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25

28 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

94
Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln
1 5 10 15
Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25

29 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

95
Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn
1 5 10 15
Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25

30 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

96
Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile
1 5 10 15
Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25 30

31 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

97
Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys
1 5 10 15
Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25 30

32 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

98
Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu
1 5 10 15
Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25 30

33 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

99
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
1 5 10 15
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
20 25 30
Leu

34 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

100
Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val
1 5 10 15
Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu
20 25 30
Leu Leu

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

101
Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln
1 5 10 15
Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp
20 25 30
Glu Leu Leu
35

36 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

102
Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser
1 5 10 15
Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser
20 25 30
Asp Glu Leu Leu
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

103
Tyr Asp Pro Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser
1 5 10 15
Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser
20 25 30
Asp Glu Leu
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“
(ix) FEATURE
(A) NAME/KEY Modified-site
(B) LOCATION 35
(D) OTHER INFORMATION /label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

104
Leu Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn
1 5 10 15
Glu Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu
20 25 30
Leu His Asn
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

105
Val Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu
1 5 10 15
Lys Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu
20 25 30
His Asn Val
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

106
Phe Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys
1 5 10 15
Ile Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu His
20 25 30
Asn Val Asn
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

107
Pro Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile
1 5 10 15
Asn Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu His Asn
20 25 30
Val Asn Ala
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

108
Ser Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn
1 5 10 15
Gln Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu His Asn Val
20 25 30
Asn Ala Gly
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

109
Asp Glu Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln
1 5 10 15
Ser Leu Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu His Asn Val Asn
20 25 30
Ala Gly Lys
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

110
Phe Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu
1 5 10 15
Ala Phe Ile Arg Lys Ser Asp Glu Leu Leu His Asn Val Asn Ala Gly
20 25 30
Lys Ser Thr
35

35 amino acids

amino acid

unknown

peptide

Modified-site

/label= A
/note= ”Preceeding this amino acid, there may be an
amino group, an acetyl group, a 9-fluorenylmethoxy-
carbonyl group, a hydrophobic group or a macromolecular
carrier group.“

Modified-site

/label= B
/note= ”Following this amino acid, there may be a
carboxyl group, an amido group, a hydrophobic group,
or a macromolecular carrier group.“

111
Asp Ala Ser Ile Ser Gln Val Asn Glu Lys Ile Asn Gln Ser Leu Ala
1 5 10 15
Phe Ile Arg Lys Ser Asp Glu Leu Leu His Asn Val Asn Ala Gly Lys
20 25 30
Ser Thr Thr
35

	Number	Date	Country
Parent	08/073028	Jun 1993	US
Child	08/255208		US

Methods for the inhibition of respiratory syncytial virus transmission

Information

Patent Number

Date Filed

Date Issued

Inventors

Original Assignees

Examiners

Agents

CPC

US Classifications

Field of Search

US

International Classifications

Abstract

Description

Claims

Parent Case Info

Government Interests

Non-Patent Literature Citations (24)

Continuation in Parts (1)

Entry
Wild et al., “A synthetic peptide inhibitor of human immunodeficiency virus replication: Correlation between solution structure and viral inhibition,” Proc. Natl. Acad. Sci. USA 89:10537-10541 1992.*
Bousse et al., “A single amino acid change enhances the fusion promotion activity of human parainfluenza virus type 1 hemagglutinin-neuraminidase glycoprotein,” Virol. 209:654-657, 1995.*
Geysen et al., “Cognitive features of continuous antigenic determinants,” J. Molec. Recog. 1:33-41, 1988.*
Wildner et al., “Database screening for molecular mimicry,” Immunol. Today18(5):251-252, 1997.*
Roudier, J., “Response to Wildner et al. and Burns et al.,” Immunol. Today 18(5):252, 1997.*
Hall, C., “Prospects for a respiratory syncytial virus vaccine,” Science 265:1393-1394, 1994.*
Toms, G., “Respiratory syncytial virus- how soon will we have a vaccine?” Arch. Dis. Child. 72:1-3, 1995.*
Benet et al., “Pharmacokinetics: the dynamics of drug absorption, distribution, and elimination,” in The Pharamcological Basis of Therapeutics, Goodman et al., eds., Pergammon Press, New York, pp. 3-32, 1990.*
Flexner, C. and C. Hendrix, 1997, “Pharmacology of antiretroviral agents”, in AIDS: Biology, Diagnosis, Treatment and Prevention, fourth edition, DeVita, V.T., et al., eds., Lippincott-Raven Publishers, pp. 479-493.*
Yarchoan, R. and S. Broder, 1992 “Correlations between the in vitro and in vivo activity of anti-HIV agents: implications for future drug development”, J. Enzyme Inhib. 6:99-111.*
Gait, M.J. and J. Karn, 1995, “Progress in anti-HIV structure-based design”, TIBTECH 13:430-438.*
Suzuki et al., 1995, “Viral Interleukin 10 (IL-10), the human Herpes Virus 4 Cellular IL-10 Homologue, Induces Local Anergy to Allogenic and Syngeneic Tumors”, J of Experimental Medicine 182:477-486.
Wild et al., 1994, “Propensity for a Leucine Zipper-Like Domain of Human Immunodeficiency Virus Type 1 gp41 to Form Oligomers Correlates With a Role in Virus-Induced Fusion Rather Than Assembly of the Glycoprotein Complex”, Proc. Natl. Acad. Sci. USA 91:12676-80.
Bousse et al., 1994, “Regions on the Hemagglutinin-Neuraminidase Proteins of Human Parainfluenza Virus Type-1 and Sendai Virus Important for Membrane Fusion”, Virology 204:506-514.
Wang et al., “Ion Channel Activity of Influenza A Virus M2 Protein: Characteriztion of the Amantidine Block”, J of Virology 67:5585-94.
Lazinski et al., 1983, “Relating Structure to Function in the Hepatitis Delta Virus Antigen”, J of Virology 67:2672-80.
White, J.M., 1992, “Membrane Fusion”, Science 258:917-924.
Daar et al., 1990, “High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates”, Proc. Natl. Acad. Sci. USA 87:6574-6579.
Erickson et al., 1990, “Design, Activity, and 2.8 Å Crystal Structure of a C2 Symmetric Inhibitor Complexed to HIV-1 Protease”, Science 249:527-533.
Smith et al., 1987, “Blocking of HIV-1 Infectivity by a Soluble, Secreted Form of the CD4 Antigen”, Science 238:1704-1707.
Collins et al., 1984, “Nucleotide Sequence of the Gene Encoding the Fusion (F) Glycoprotein of Human Respiratory Syncytial Virus”, Proc. Natl. Acad. Sci. USA 81:7683-87.
Staden, 1994, “Searching for Motifs in Protein Sequences”, Chapter 12 in: Methods in Molecular Biology, vol. 25, Griffin et al., eds., Humana Press, Inc., Totowa, NJ, p. 131-139.
Staden, 1994, “Using Patterns to Analyze Protein Sequences”, Chapter 13 in: Methods in Molecular Biology, vol. 25, Griffin et al., eds., Humana Press, Inc., Totowa, NJ, p. 141-154.
Staden, 1990, “Searching for Patterns in Protein and Nucleic Acid Sequences”, Meth. Enzymol. 183:193-211.