HIV-1 envelope glycoprotein fusion peptide region (FP (commonly used; "fusion peptide" or "FP" of HIV-1 Env gp41 subunit))

The HIV-1 envelope glycoprotein fusion peptide region refers to a highly conserved, hydrophobic sequence (the fusion peptide, FP) at the N-terminus of the gp41 subunit of the HIV-1 envelope glycoprotein complex (Env)[5][6]. Env is initially synthesized as gp160 and then cleaved by host proteases into gp120 (responsible for receptor binding) and gp41 (which mediates membrane fusion)[3][5][6]. Upon CD4 and coreceptor binding, conformational changes expose the fusion peptide, which inserts into the host cell membrane, initiating the process of membrane fusion required for HIV-1 entry[3][5][7]. The gp41 fusion peptide undergoes further conformational transitions, eventually leading to the formation of a six-helix bundle that apposes and fuses the viral and host membranes[2][3][4]. The fusion peptide is a key target for peptide fusion inhibitors (notably enfuvirtide, T-20) and several broadly neutralizing antibodies, making it a primary focus for drug development and vaccine design[5][6][7]. Its essential role in viral infectivity and highly conserved structure make it an attractive but technically challenging therapeutic target[5][6][7].

Other names

Fusion peptide (FP) of gp41HIV-1 Env fusion peptidegp41 fusion peptide

Inhibition of conformational transitions required for membrane fusion (e.g., preventing six-helix bundle formation in gp41) Steric blocking of fusion peptide insertion into host cell membrane by antibodies or small molecules Stabilizing prefusion states or blocking post-fusion conformational changes