Compounds which inhibit HIV replication

Abstract

This invention relates to human immunodeficiency virus (HIV) protein fragments which have antiviral activity, and particularly relates to HIV peptides derived from the HIV transmembrane glycoprotein (gp41) which inhibit HIV-induced cell-cell fusion. This invention further relates to methods for the inhibition of enveloped viral infection, and to methods that modulate biochemical processes which involve coiled coil peptide interactions.

What is claimed is:  
     
         1 . An isolated peptide comprising a DP-107 amino acid sequence listed in SEQ ID:1.  
     
     
         2 . An isolated peptide ranging from about 14 to about 60 amino acids in length, capable of forming a heterodimer with the peptide of  claim 1 .  
     
     
         3 . The peptide of  claim 1  or  2  wherein the amino terminus of the peptide is acetylated.  
     
     
         4 . The peptide of  claim 1  or  2  wherein the carboxy terminus of the peptide is amidated.  
     
     
         5 . An isolated multimer of the peptide of  claim 1  or  2 .  
     
     
         6 . The multimer of  claim 5  wherein the multimer is a tetramer.  
     
     
         7 . The multimer of  claim 5  wherein the multimer is a dimer consisting of two peptide monomers.  
     
     
         8 . The dimer of  claim 6  wherein the monomers of the dimer are covalently bound to one another.  
     
     
         9 . A method for inhibiting HIV-induced cell fusion comprising contacting an HIV-infected cell with an effective amount of a peptide comprising a DP-107 amino acid sequence listed in SEQ ID:1 so that the cell fusion is inhibited.  
     
     
         10 . The method of  claim 9  wherein the HIV is HIV-1.  
     
     
         11 . A method for inhibiting HIV-induced cell fusion comprising contacting an HIV-infected cell with an effective amount of a peptide comprising the peptide of  claim 2  so that the cell fusion is inhibited.  
     
     
         12 . The method of  claim 11  wherein the HIV is HIV-1.  
     
     
         13 . The method of  claim 9  wherein the peptide is present as a multimer.  
     
     
         14 . The method of  claim 11  wherein the peptide is present as a multimer.  
     
     
         15 . The method of  claim 13  or  14  wherein the multimer is a dimer having two peptide monomers.  
     
     
         16 . The method of  claim 12  wherein the monomers are covalently bound to one another.  
     
     
         17 . A method for testing compounds capable of inhibiting the ability of HIV to infect cells, comprising: 
 (a) contacting a test compound to a multimer of a peptide comprising a DP-107 amino acid sequence listed in SEQ ID:1; and    (b) detecting whether the test compound disrupts the multimer, the ability of the test compound to disrupt the multimer indicating the test compound is capable of inhibiting HIV infection of cells.    
     
     
         18 . The method of  claim 17  wherein the HIV is HIV-1.  
     
     
         19 . The method of  claim 17  wherein the multimer is a dimer or a tetramer.  
     
     
         20 . The method of  claim 17  wherein the contacting step is carried out in an aqueous solution.  
     
     
         21 . A method for testing compounds capable of inhibiting the ability of HIV to infect cells, comprising: 
 (a) contacting a test compound to a multimer of the peptide of  claim 2;  and    (b) detecting whether the test compound disrupts the multimer, the ability of the test compound to disrupt the multimer indicating the test compound is capable of inhibiting HIV infection of cells.    
     
     
         22 . The method of  claim 21  wherein the HIV is HIV-1.  
     
     
         23 . The method of  claim 21  wherein the multimer is a dimer or a tetramer.  
     
     
         24 . The method of  claim 21  wherein the contacting step is carried out in an aqueous solution.  
     
     
         25 . A method for inhibiting enveloped viral infection comprising contacting an uninfected cell with an effective amount of a peptide capable of contributing to the formation of a coiled coil peptide structure so that an enveloped virus is inhibited from infecting the uninfected cell.  
     
     
         26 . The method of  claim 25  wherein the enveloped virus is a retrovirus.  
     
     
         27 . The method of  claim 26  wherein the retrovirus is HIV-2, HTLV-I, or HTLV-II.  
     
     
         28 . The method of  claim 25  wherein the enveloped virus is an influenza virus.  
     
     
         29 . The method of  claim 25  wherein the enveloped virus is a respiratory syncytial virus.  
     
     
         29 . A method for testing compounds capable of inhibiting the ability of an enveloped virus to infect cells, comprising: 
 (a) contacting a test compound to a multimer of a peptide capable of contributing to the formation of a coiled coil peptide structure; and    (b) detecting whether the test compound disrupts the multimer, the ability of the test compound to disrupt the multimer indicating the test compound is capable of inhibiting enveloped viral infection of cells.    
     
     
         30 . The method of  claim 29  wherein the enveloped virus is a retrovirus.  
     
     
         31 . The method of  claim 30  wherein the retrovirus is HIV-2, HTLV-I, or HTLV-II.  
     
     
         32 . The method of  claim 29  wherein the enveloped virus is an influenza virus.  
     
     
         33 . The method of  claim 29  wherein the multimer is a dimer or a tetramer.  
     
     
         34 . The method of  claim 29  wherein the contacting step is carried out in an aqueous solution.