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

The Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) is a trimeric complex composed of gp120 and gp41 subunits that mediates viral entry into host cells [Source: UniProt P04578]. The CD4-binding site (CD4bs) is a highly conserved region on the gp120 subunit that serves as the primary attachment point for the host CD4 receptor [Source: PubMed PMC4289608]. Binding of CD4 to this site induces conformational changes in the Env trimer, transitioning it from a closed state to an open state that exposes the coreceptor binding site [Source: Nature 1998, 393(6686)]. This site is a major target for drug development, including small-molecule attachment inhibitors like Fostemsavir and broadly neutralizing antibodies (bNAbs) such as VRC01 and 3BNC117 [Source: NIH/NIAID]. These therapeutics function by blocking the initial interaction between the virus and the CD4+ T-cell, thereby preventing viral entry and subsequent replication. However, the high mutation rate of HIV-1 and the presence of a dense glycan shield can lead to the development of resistance, necessitating the use of these agents as part of combination antiretroviral therapy [Source: Lancet HIV 2020].

Other names

CD4 binding sitegp120 CD4-binding siteHIV-1 Env CD4bsCD4bs

Attachment inhibition through steric hindrance of the gp120-CD4 interaction [Source: PubChem CID 71245230]