Human immunodeficiency virus type 1 glycoprotein 120 CD4 binding site (HIV-1 gp120 CD4bs)

The Human immunodeficiency virus type 1 glycoprotein 120 (gp120) CD4 binding site is a critical functional domain on the viral envelope protein responsible for initiating infection by binding to the host CD4 receptor (UniProt P04578). This interaction triggers a series of conformational changes in the envelope trimer, exposing the coreceptor binding site and facilitating viral fusion with the host cell membrane (PubMed: 21179084). As a highly conserved region essential for viral entry, it serves as a primary target for both small-molecule inhibitors and broadly neutralizing antibodies (bNAbs). Fostemsavir, a prodrug of temsavir, is a first-in-class attachment inhibitor that binds directly to this site to prevent the initial docking of the virus to CD4+ T-cells (PubChem CID 71241277). Additionally, potent bNAbs such as VRC01 and 3BNC117 target this epitope to neutralize a wide range of HIV-1 variants, making it a focal point for vaccine design and passive immunization strategies (NIH: NIAID). Despite its importance, the site is shielded by a complex layer of glycans and variable loops, which the virus uses to evade host immune detection. Therapeutic challenges include the emergence of resistance mutations within the gp120 sequence that can reduce drug affinity or antibody neutralization potency.

Other names

gp120 CD4 binding siteCD4bsHIV-1 envelope glycoprotein gp120 CD4 binding pocketCD4-binding site of gp120

Inhibition of viral attachment to host CD4+ cells by binding to the gp120 subunit of the HIV-1 envelope glycoprotein, preventing the conformational change required for CD4 receptor interaction (PubChem CID 71241277).