Multimerization of HIV-1 Vif protein as a therapeutic target

Abstract

One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif, by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle. In preferred embodiments, the compound or compounds that interactively block the multimerization domain of Vif are Vif antagonists. Pharmaceutical compositions comprising these compounds are also disclosed.

What is claimed is:  
     
         1 . A Vif antagonist that binds to the multimerization domain within a Vif protein in a cell and inhibits Vif protein multimerization, wherein said antagonist is a peptide selected from the group consisting of SEQ. ID. NO: 5; SEQ. ID. NO: 6; SEQ. ID. NO: 7; SEQ. ID. NO: 8; SEQ. ID. NO: 9; SEQ. ID. NO: 10; SEQ. ID. NO: 12; SEQ. ID. NO: 13; SEQ. ID. NO: 14; SEQ. ID. NO: 15; SEQ. ID. NO: 16; SEQ. ID. NO: 17; SEQ. ID. NO: 18; SEQ. ID. NO: 19; SEQ. ID. NO: 20; SEQ. ID. NO: 21; SEQ. ID. NO: 22; and SEQ. ID. NO: 23.  
     
     
         2 . The Vif antagonist of  claim 1 , wherein the antagonist is SEQ. ID. NO: 9.  
     
     
         3 . The Vif antagonist of  claim 1 , wherein the antagonist is SEQ. ID. NO:13.  
     
     
         4 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a Vif antagonist of  claim 1.