design of small molecules with hiv fusion inhibitory property based on gp41 interaction assay

Design of Small Molecules with HIV Fusion Inhibitory Property Based on Gp41 Interaction Assay

BACKGROUND Gp41 of HIV (Human Immunodeficiency Virus) is a protein that mediates fusion between viral and cellular membranes. The agent, T-20, which has been approved for HIV inhibition, can restrain Gp41 function in the fusion process; nevertheless, it has disadvantages like instability, high cost of production and injection form to be delivered twice a day. METHODS Several molecules like NB...

INTERACTION OF PROTEINS WITH SMALL MOLECULES

Small molecules that bind the inner core of gp41 and inhibit HIV envelope-mediated fusion.

HIV-1 enters cells by membrane fusion, mediated by the trimeric viral envelope glycoprotein gp160, which is processed by a single proteolytic cleavage into stably associated gp120 and gp41. The gp120/gp41 trimer can be triggered to undergo an irreversible conformational change. Using a protein-based assay designed to mimic the gp41 conformational change, we screened for small molecules that pre...

A novel chimeric protein-based HIV-1 fusion inhibitor targeting gp41 with high potency and stability

A novel chimeric protein-based HIV-1 fusion inhibitor targeting gp41 with high potency and stability Chungen Pan, Lifeng Cai, Hong Lu, Lu Lu, and Shibo Jiang* From Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065 MOE/MOH Key Laboratory of Medical Molecular Virology and Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032,...

Asymmetric Deactivation of HIV-1 gp41 following Fusion Inhibitor Binding

Both equilibrium and nonequilibrium factors influence the efficacy of pharmaceutical agents that target intermediate states of biochemical reactions. We explored the intermediate state inhibition of gp41, part of the HIV-1 envelope glycoprotein complex (Env) that promotes viral entry through membrane fusion. This process involves a series of gp41 conformational changes coordinated by Env intera...

Design of a highly potent HIV-1 fusion inhibitor targeting the gp41 pocket.

OBJECTIVE T20 (Enfuvirtide), which is a 36-residue peptide derived from the C-terminal heptad repeat (CHR) of gp41, is the only clinically available HIV-1 fusion inhibitor, but it easily induces drug resistance, which calls for next-generation drugs. DESIGN We recently demonstrated that the M-T hook structure can be used to design a short CHR peptide that specifically targets the conserved gp...