SARS-CoV-2 spike protein ectodomain (SARS-CoV-2 S protein)

The SARS-CoV-2 spike (S) protein ectodomain is a class I fusion protein that mediates viral entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor (UniProt P0DTC2). While the Receptor Binding Motif (RBM) is the primary site for ACE2 interaction, the regions outside the RBM—including the N-terminal domain (NTD) and the S2 subunit—are essential for the structural transitions required for membrane fusion (Harvey et al., Nature Reviews Microbiology, 2021). These non-RBM regions are generally more conserved across viral variants, making them high-priority targets for broadly neutralizing antibodies (bnAbs) (Pinto et al., Science, 2021). Therapeutic agents like Sotrovimab target conserved epitopes within the RBD but outside the RBM, effectively neutralizing the virus by preventing membrane fusion or sterically hindering receptor access (Cathcart et al., Nature, 2022). Targeting these regions is a key strategy for developing therapeutics that maintain efficacy against emerging SARS-CoV-2 variants of concern.

Other names

Spike glycoproteinS-proteinSurface glycoproteinSARS-CoV-2 S ectodomainNon-RBM spike epitopes

Inhibition of viral-host membrane fusion and neutralization of viral entry through steric hindrance of receptor binding or stabilization of the pre-fusion conformation.