Human immunodeficiency virus type 1 envelope glycoprotein gp120 CD4 binding site (HIV-1 gp120 CD4bs)

The Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 CD4 binding site (CD4bs) is a highly conserved and functionally critical epitope on the surface of the HIV-1 virion [1, 4]. It serves as the primary attachment point for the host cell's CD4 receptor, initiating the viral entry process by triggering conformational changes in the envelope trimer that allow for subsequent co-receptor binding and membrane fusion [2, 5]. Because of its essential role in infection, the CD4bs is a major target for therapeutic intervention, including small-molecule inhibitors and broadly neutralizing antibodies (bNAbs) [1, 12]. Drugs such as fostemsavir (and its active metabolite temsavir) bind to this site to prevent the virus from attaching to CD4+ T cells [1, 15]. Additionally, several bNAbs like VRC01 and 3BNC117 are designed to mimic the CD4 receptor's interaction, providing broad neutralization across various HIV-1 strains [4, 7]. However, the target's structural complexity, including extensive glycosylation and conformational masking, facilitates the development of resistance mutations that pose a significant challenge to long-term efficacy [1, 6].

Other names

CD4 binding siteCD4bsgp120 CD4-binding pocketPhe43 cavityCD4-binding domain

Inhibition of viral attachment to the host CD4 receptor by sterically blocking the binding site or stabilizing the envelope glycoprotein in a non-functional conformation [1, 15].