Human Immunodeficiency Virus type 1 Envelope Glycoprotein 41 (gp41)

HIV envelope protein gp41 is a transmembrane glycoprotein that forms part of the HIV-1 envelope (Env) spike complex, which is essential for viral entry into host cells. The Env complex consists of three gp120 surface subunits non-covalently associated with three gp41 transmembrane subunits, forming a trimeric structure on the viral surface. gp41 mediates fusion between the viral envelope and host cell membranes following receptor engagement by gp120. Upon binding CD4 and coreceptor on target cells, conformational changes expose the hydrophobic fusion peptide of gp41, which inserts into the cellular membrane. Subsequent refolding brings together heptad repeat regions to form a stable six-helical bundle, drawing viral and cellular membranes together until they fuse—allowing entry of viral contents into the cell cytoplasm. Because formation of its characteristic helical bundles is essential for function, small molecules or peptides targeting these interfaces can block infection at an early stage. The high conservation within its ectodomain further supports its value as a drug/vaccine target.

Inhibition of gp41-mediated membrane fusion