Human immunodeficiency virus type 1 glycoprotein 41 N-heptad repeat hydrophobic pocket (HIV-1 gp41 NHR pocket)

The HIV-1 gp41 N-heptad repeat (NHR) hydrophobic pocket is a critical structural element within the transmembrane subunit of the HIV-1 envelope glycoprotein (Env). During the process of viral entry, gp41 undergoes a major conformational change where three NHR helices form a central trimeric coiled-coil, creating three deep hydrophobic grooves that contain a highly conserved 'pocket' at their C-terminal end. This pocket serves as a vital docking site for the C-heptad repeat (CHR) region of gp41, facilitating the formation of a stable six-helix bundle (6-HB) that brings the viral and cellular membranes into close proximity for fusion. Because this pocket is highly conserved across different HIV-1 strains and is essential for viral infectivity, it is a primary target for the development of fusion inhibitors. Drugs targeting this site, including various peptides and small molecules, work by binding to the pocket and preventing the NHR-CHR interaction, thereby blocking the transition to the fusion-active state and preventing the virus from entering the host cell.

Other names

gp41 NHR hydrophobic pocketgp41 hydrophobic pocketgp41 N-terminal heptad repeat pocketHIV-1 gp41 fusion pocketgp41 N-heptad repeat (NHR) pocket

Inhibition of six-helix bundle (6-HB) formation by competitively binding to the NHR hydrophobic pocket, thereby preventing viral-cell membrane fusion.