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

The HIV-1 gp120 CD4-binding site (CD4bs) is a critical functional domain on the surface of the human immunodeficiency virus type 1 envelope glycoprotein (UniProt P04578). It serves as the primary attachment point for the virus to the host's CD4 receptor, which is predominantly expressed on T-helper lymphocytes and macrophages (NIH, 2023). Upon binding to CD4, gp120 undergoes a series of conformational changes that expose the co-receptor binding site (CCR5 or CXCR4), eventually leading to viral fusion and entry into the host cell (PubMed: 29434336). Because this site is essential for viral infectivity and is relatively conserved across different HIV-1 strains, it is a major target for both small-molecule inhibitors and broadly neutralizing antibodies (bNAbs) (Nature, 2016). Drugs like fostemsavir (and its active moiety temsavir) specifically target this site to prevent the initial attachment of the virus (FDA, 2020). Additionally, many potent bNAbs under clinical investigation, such as VRC01, are designed to recognize and block this specific epitope to neutralize the virus (NIH, 2021). However, the high mutation rate of the HIV-1 envelope remains a significant challenge, as it can lead to the emergence of resistant variants that evade these therapeutic interventions (PubMed: 31209115).

Other names

CD4-binding siteCD4bsgp120 CD4-binding pocketHIV-1 gp120 surface glycoprotein CD4-binding site

Attachment inhibition by preventing the interaction between the viral gp120 protein and the host CD4 receptor, thereby blocking viral entry into the target cell (FDA, 2020).