Probing the Interaction Between HIV-1 Surface Envelope Glycoprotein gpl20 and Its Cell Co-Receptor CCR5 Using Photoactivatable CCR5-Derived Peptides to Guide Discovery and Optimization of Novel HIV-1 Entry Inhibitors

摘要

All successful anti-HIV strategies to date have focused either on (A) three viral enzymes - reverse transcriptase, integrase, and protease, or (B) the process of viral entry - steps of binding to the surface of the host cell and fusion of the viral and cellular membranes. Viral envelope glycoproteins gp120 and gp41, encoded by env gene, are key players in the entry process. gp120 attaches to the CD4 receptor as well as binds the CCR5 and/or CXCR4 co-receptors, while gp41 mediates the fusion step. Currently, among the 37 FDA-approved anti-HIV drugs, only 2 target the fusion process: the entry inhibitor Maraviroc (Selzentry) and the fusion inhibitor Enfuvirtide (Fuzeon).