Human immunodeficiency virus type 1 glycoprotein 41 fusion peptide (HIV-1 gp41 FP)

The HIV-1 fusion peptide (FP) is a highly conserved, hydrophobic sequence located at the N-terminus of the gp41 transmembrane subunit of the HIV-1 envelope glycoprotein (Env) [6, 8]. It plays a critical role in the viral entry process by inserting into the host cell membrane following the binding of the gp120 subunit to CD4 and coreceptors (CCR5 or CXCR4) [12, 17]. This insertion initiates the fusion of the viral and cellular membranes, allowing the viral capsid to enter the host cytoplasm [11, 18]. Because of its essential role and high conservation across different HIV-1 strains, the fusion peptide is a major site of vulnerability and a target for therapeutic intervention [2, 16]. Broadly neutralizing antibodies, such as VRC34.01, and experimental peptide inhibitors, such as VIR-576, specifically target this region to block membrane fusion and prevent infection [4, 9, 16]. Developing drugs against this target is a key strategy for overcoming resistance to existing antiretroviral therapies [1, 11].

Other names

gp41 fusion peptideHIV-1 FPN-terminal fusion peptide of gp41gp41 fusion domain

Inhibition of viral-cell membrane fusion by blocking the insertion of the fusion peptide into the host cell membrane or preventing the conformational changes required for fusion.