Severe acute respiratory syndrome coronavirus 2 Spike glycoprotein (non-RBD regions) (SARS-CoV-2 S (non-RBD))

The SARS-CoV-2 Spike (S) glycoprotein is a trimeric class I fusion protein that mediates viral entry into host cells. While the Receptor Binding Domain (RBD) is the primary site for ACE2 binding, the regions outside the RBD, including the N-terminal domain (NTD) and the S2 subunit, are critical for viral attachment and membrane fusion (UniProt: P0DTC2). The NTD is involved in initial cell surface interactions and acts as a wedge to regulate the conformational dynamics of the RBD (Chi et al., Science 2020). The S2 subunit contains the fusion peptide and heptad repeat regions, which undergo a massive structural transition to facilitate the merging of viral and host membranes (Pinto et al., Science 2021). Because the S2 subunit is highly conserved across various coronavirus strains, it is an attractive target for developing broadly neutralizing antibodies that could remain effective against emerging variants (Harvey et al., Nature Reviews Microbiology 2021). Current vaccines and certain experimental monoclonal antibodies target these non-RBD regions to prevent infection by inhibiting these essential entry steps.

Other names

SARS-CoV-2 Spike protein N-terminal domainSARS-CoV-2 Spike protein S2 subunitSARS-CoV-2 S protein non-RBD domainsSARS-CoV-2 S1-NTDSARS-CoV-2 S2 fusion protein

Neutralization of viral infection by blocking N-terminal domain (NTD) mediated attachment or inhibiting S2 subunit mediated membrane fusion between the virus and host cell.