SARS-CoV-2 spike glycoprotein (Beta variant) (SARS-CoV-2 S protein)

The SARS-CoV-2 spike (S) protein is a class I fusion glycoprotein responsible for viral attachment to the host ACE2 receptor and subsequent membrane fusion (UniProt P0DTC2). This specific mutant form, featuring K417N, E484K, N501Y, and D614G, is characteristic of the B.1.351 (Beta) variant of concern (CDC, 2021). The N501Y mutation increases the binding affinity for the ACE2 receptor, while the E484K and K417N mutations in the receptor-binding domain (RBD) significantly contribute to immune escape from neutralizing antibodies (Wang et al., 2021, Nature). The D614G mutation enhances viral infectivity by stabilizing the spike trimer in an "up" conformation, facilitating easier receptor access (Harvey et al., 2021, Nature Reviews Microbiology). This protein is the primary target for COVID-19 vaccines and monoclonal antibody therapies like Sotrovimab and Evusheld (NIH, 2022). However, the presence of the E484K mutation notably reduces the efficacy of certain early-generation antibodies such as Bamlanivimab and the Casirivimab/Imdevimab cocktail (Hoffmann et al., 2021, Cell). Understanding these mutations is critical for the development of next-generation vaccines and variant-proof therapeutics.

Other names

SARS-CoV-2 spike protein (B.1.351)Beta variant spike proteinS proteinSurface glycoproteinSARS-CoV-2 S protein (K417N/E484K/N501Y/D614G)

Neutralization of viral entry by blocking the interaction between the receptor-binding domain (RBD) and the host ACE2 receptor, or by inhibiting membrane fusion.