Human immunodeficiency virus type 1 envelope glycoprotein gp120 (HIV-1 gp120) (HIV-1 gp120)

The Human Immunodeficiency Virus type 1 (HIV-1) envelope glycoprotein gp120 is the surface subunit of the viral Env protein complex, which is essential for the virus's ability to infect host cells (UniProt P04578). It functions by mediating the initial high-affinity binding to the host CD4 receptor, which induces conformational changes in the Env trimer that allow for subsequent binding to co-receptors such as CCR5 or CXCR4 (Scheid et al., 2011, Science). This sequence of events is a prerequisite for the fusion of the viral and host cell membranes, a process facilitated by the transmembrane subunit gp41. Because gp120 is the most exposed component of the virus, it is the primary target for the host's neutralizing antibody response and a central focus for the development of entry inhibitors and vaccines. 3BNC117-LS is a potent, broadly neutralizing monoclonal antibody (bNAb) that specifically targets the highly conserved CD4 binding site (CD4bs) on gp120 (Caskey et al., 2015, Nature). By mimicking the interaction of the CD4 receptor, 3BNC117-LS sterically blocks the virus from attaching to its target cells, effectively neutralizing a wide range of global HIV-1 strains. The LS modification in the antibody's Fc region (M428L/N434S) enhances its binding to the neonatal Fc receptor (FcRn), thereby significantly extending its half-life in human circulation (Gaudinski et al., 2019, PLOS Medicine).

Other names

gp120HIV-1 EnvSurface protein SUEnvelope glycoprotein gp120Env surface subunit

Drugs targeting gp120 primarily function as entry inhibitors. Broadly neutralizing antibodies like 3BNC117-LS bind to the CD4 binding site (CD4bs) of gp120, sterically hindering the virus's ability to attach to the host CD4 receptor (Scheid et al., 2011, Science). Other agents, such as attachment inhibitors (e.g., fostemsavir), bind directly to gp120 to prevent the initial interaction with CD4, while some antibodies target the V3 loop or the membrane-proximal external region (MPER) to inhibit co-receptor binding or fusion (Caskey et al., 2015, Nature).