Peptide viral entry inhibitors

Abstract

The present invention provides, inter alia, peptide compositions and methods for treating and preventing Flaviviridae virus (e.g., HCV) infections.

1 . An isolated polypeptide:
 (i) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 82-84, 87-97, 99, 101-103 and 117-138; or   (ii) consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-81, 85, 86, 98, 100, 104-116 and 139.   
     
     
         2 . The isolated polypeptide of  claim 1 :
 (i) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 82-84, 87-97, 99, 101-103, 117-130 and 132-138; or   (ii) consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 3, 7, 9, 10, 12-28, 30-38, 40, 42, 44-60, 62-68, 70-81, 85, 86, 98, 100 and 106-116.   
     
     
         3 . A pharmaceutical composition comprising the polypeptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         4 . A composition comprising the polypeptide of  claim 1  in association with one or more members selected from the group consisting of anti-human CD81 antibody, ribavirin, interferon alfa-2a, interferon alfa-2b, interferon alfa-2c, interferon alfa n-1, interferon alfa n-3, consensus interferon, pegylated interferon alfa-2a, pegylated interferon alfa-2b, pegylated interferon alfa-2c, pegylated interferon alfa n-1, pegylated interferon alfa n-3, and pegylated consensus interferon. 
     
     
         5 . A kit comprising a polypeptide of  claim 1  and a member selected from the group consisting of anti-human CD81 antibody, ribavirin, interferon alfa-2a, interferon alfa-2b, interferon alfa-2c, interferon alfa n-1, interferon alfa n-3, consensus interferon, pegylated interferon alfa-2a, pegylated interferon alfa-2b, pegylated interferon alfa-2c, pegylated interferon alfa n-1, pegylated interferon alfa n-3, and pegylated consensus interferon. 
     
     
         6 . An isolated polynucleotide encoding the polypeptide of  claim 1 . 
     
     
         7 . A recombinant vector comprising the polynucleotide of  claim 6 . 
     
     
         8 . An isolated host cell comprising the vector of  claim 7 . 
     
     
         9 . A method for making a polypeptide comprising culturing a host cell of  claim 8  under conditions in which the polynucleotide is expressed. 
     
     
         10 . The method of  claim 9  wherein the polypeptide is isolated from the culture. 
     
     
         11 . A method for inhibiting entry of a virus which is a member of the Flaviviridae family into a cell comprising contacting the cell with a polypeptide of  claim 1 . 
     
     
         12 . The method of  claim 11  wherein the cell is in vitro. 
     
     
         13 . A method for treating or preventing infection of a subject with a virus which is a member of the Flaviviridae family comprising administering to said subject a therapeutically effective amount of a polypeptide of  claim 1 . 
     
     
         14 . The method of  claim 13  wherein the subject is a human. 
     
     
         15 . The method of  claim 13  wherein the virus is hepatitis C virus. 
     
     
         16 . The method of  claim 13  wherein the polypeptide is administered to the subject parenterally. 
     
     
         17 . The method of  claim 16  wherein the polypeptide is administered to the subject intramuscularly, intravenously or subcutaneously. 
     
     
         18 . The method of  claim 13  wherein said polypeptide is administered in association with one or more members selected from the group consisting of anti-human CD81 antibody, ribavirin, interferon alfa-2a, interferon alfa-2b, interferon alfa-2c, interferon alfa n-1, interferon alfa n-3, consensus interferon, pegylated interferon alfa-2a, pegylated interferon alfa-2b, pegylated interferon alfa-2c, pegylated interferon alfa n-1, pegylated interferon alfa n-3, and pegylated consensus interferon. 
     
     
         19 . The method of  claim 15  wherein said polypeptide is administered for a treatment time period sufficient to eradicate detectable hepatitic C virus-RNA and to maintain no detectable hepatitic C virus RNA for at least twelve weeks after the end of the treatment time period. 
     
     
         20 . The method of  claim 15  wherein said polypeptide is administered in association with a therapeutically effective amount of an interferon for a treatment time period sufficient to eradicate detectable hepatitic C virus-RNA and to maintain no detectable hepatitic C virus RNA for at least twelve weeks after the end of the treatment time period. 
     
     
         21 . The method of  claim 15 , wherein the host is infected with multiple hepatitis C virus genotypes. 
     
     
         22 . The method of  claim 21 , wherein the host is infected with hepatitis C virus genotype 1 hepatitis C virus genotype 2 or hepatitis C virus genotype 3. 
     
     
         23 . The method of  claim 13  wherein the subject is co-infected with human immunodeficiency virus (HIV). 
     
     
         24 . A method for treating or preventing infection of a subject, with a virus which is a member of the Flaviviridae family of viruses, following transplantation of a liver into said host or transfusion of blood into said subject comprising administering to said subject a therapeutically effective amount of a polypeptide of  claim 1 . 
     
     
         25 . The method  claim 24  wherein the virus is hepatitis C virus. 
     
     
         26 . The method of  claim 24  wherein the polypeptide is administered in association with a member selected from the group consisting of anti-human CD81 antibody, ribavirin, interferon alfa-2a, interferon alfa-2b, interferon alfa-2c, interferon alfa n-1, interferon alfa n-3, consensus interferon, pegylated interferon alfa-2a, pegylated interferon alfa-2b, pegylated interferon alfa-2c, pegylated interferon alfa n-1, pegylated interferon alfa n-3, and pegylated consensus interferon. 
     
     
         27 . The method of  claim 24  wherein the polypeptide is administered to the subject parenterally. 
     
     
         28 . The method of  claim 27  wherein the polypeptide is administered to the subject intramuscularly, intravenously or subcutaneously.