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HIV gp41

The envelope glycoprotein of HIV-1 consists of two proteins - gp120 and gp41. This gp120 determines viral tropism by binding to target-cell receptors CD4, whereas gp41 is responsible for viral entry into the cell. In recent year, Envelope glycoprotein gp41 has emerged a conserved target for defense against HIV. When Envelope glycoprotein gp120 at the viral surface bind to the cell, gp41, undergoes a major conformational change in to a fusion active state (trimeric coiled coil), which mediates fusion of viral and cellular membrane. Crystal structure of a peptide, representing fusion active conformation of gp41 is a trimeric coiled coil, with a hydrophobic cluster at its base, and C-terminal peptide, pack in an anti-parallel orientation against coiled coil. By disrupting the interactions between trimeric coiled-coil and c-terminal peptide - particularly focusing hydrophobic cavity at its base, offers an attractive target for defense against HIV. As gp41 shares strong structural similarity with transmemenrane glycoproteins of other  virus such as Leukemia, Influenza and Ebola, development of fusion inhibitors is also an attractive mechanics for defense against these dieseases .

FIG:  HIV fusion inhibitor targets. Drug targets on HIV Env can be classified into three groups: 1) Those that are present in native gp120 and gp41. 2) Those exposed in gp120 following CD4 binding. 3) Those exposed in triggered gp41 (as in T-20 peptide inhibition).


Important HIV entry Inhibitors

C20 peptide [by Peter Kim provide link]

  1. Core Structure of gp41 from the HIV Envelope Glycoprotein Cell, Vol. 89, 263–273, April 18, 1997, David C. Chan,* Deborah Fass,* James M. Berger,* to generate a receptor-bindingsubunit (HA1) and a membrane-and Peter S. Kim*.doi: 10.1016/S0092-8674(00)80205-6

  2. "Validation of a Novel Approach for HIV-1 Fusion Inhibitor Drug Discovery" Reported by Jules Levin XVI IAC Toronto, Aug 2006