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

The Human immunodeficiency virus 1 (HIV-1) envelope glycoprotein gp120 CD4-binding site is a critical functional domain on the surface of the virus responsible for the initial step of infection (UniProt: P04578). It facilitates the high-affinity interaction between the viral envelope (Env) trimer and the CD4 receptor on host cells, such as T-helper lymphocytes and macrophages (PubMed: 25533457). Upon binding, the CD4-binding site undergoes conformational changes that expose the coreceptor binding site, ultimately leading to viral-cell membrane fusion and entry (PubMed: 20616233). Because of its essential role in the viral life cycle and its relatively conserved nature across different HIV-1 strains, this site is a primary target for broadly neutralizing antibodies (bNAbs) and small-molecule entry inhibitors (PubMed: 32103171). Drugs like Temsavir bind directly to gp120 near this site to prevent the initial attachment of the virus to the host cell (FDA: Fostemsavir Prescribing Information). Therapeutic strategies targeting this site aim to reduce viral load and prevent the progression of HIV infection to AIDS, particularly in patients with limited treatment options due to multidrug resistance (PubMed: 30901557).

Other names

CD4-binding site of gp120CD4bsHIV-1 Env CD4-binding sitegp120 CD4-binding pocket

Attachment inhibition via steric hindrance of the gp120-CD4 interaction