SARS-CoV-2 spike protein S1 subunit (non-RBM regions) (SARS-CoV-2 S1 (non-RBM))

The SARS-CoV-2 spike protein S1 subunit is the primary surface glycoprotein of the virus, facilitating attachment to host cells via the angiotensin-converting enzyme 2 (ACE2) receptor. While the receptor-binding motif (RBM) is the direct interface for ACE2, the regions of the S1 subunit outside the core RBM, including the N-terminal domain (NTD) and conserved lateral surfaces of the receptor-binding domain (RBD), are critical for viral stability and immune evasion (UniProt P0DTC2). These non-RBM regions are significant therapeutic targets because they often harbor highly conserved epitopes that are less prone to the rapid mutations seen within the RBM (Pinto et al., Nature 2020). Monoclonal antibodies such as Sotrovimab target these conserved sites to provide broad-spectrum neutralization against multiple SARS-CoV-2 variants. By binding to these regions, therapeutic agents can sterically hinder receptor access or inhibit the structural transitions necessary for the S2 subunit to initiate membrane fusion (Tortorici et al., Nature 2020). Consequently, targeting the S1 subunit outside the RBM is a major focus for developing variant-resistant biologics and vaccines.

Other names

SARS-CoV-2 S1 subunitSpike protein S1N-terminal domain (NTD)Non-RBM Receptor Binding DomainS1 subunitSARS-CoV-2 S1 non-receptor binding motif regions

Neutralization of viral entry by binding to conserved epitopes outside the receptor-binding motif (RBM), which sterically hinders ACE2 receptor access or prevents the conformational changes required for S2-mediated membrane fusion (Pinto et al., Nature 2020).