Viral fusion process protein gp41 (gp41)

gp41 is a transmembrane glycoprotein that plays a central role in the entry of HIV-1 into host cells by mediating the fusion of viral and cellular membranes. It is part of the envelope glycoprotein complex (Env) of HIV-1, which consists of two subunits: gp120 (surface, responsible for receptor binding) and gp41 (transmembrane, responsible for membrane fusion). Upon activation, segments from HR1 and HR2 fold into an antiparallel six-helical bundle—a trimeric coiled-coil structure essential for membrane fusion. Its activity provides most of the free energy required to overcome kinetic barriers for merging lipid bilayers—an essential step in establishing infection. Inhibitors targeting HR regions can block six-helical bundle formation—preventing virus entry. MPER-specific broadly neutralizing antibodies can bind transitional states or block final refolding steps necessary for complete membrane merger. These features make it an attractive target for antiviral drugs and vaccine design efforts.

Inhibition of six-helical bundle formation, prevention of virus entry, blockade of final refolding steps necessary for complete membrane merger