Severe acute respiratory syndrome coronavirus 2 spike protein (SARS-CoV-2 S protein), S2 subunit and non-RBD regions (SARS-CoV-2 S protein)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is a large, trimeric class I fusion glycoprotein that is essential for viral entry into host cells (UniProt P0DTC2). It consists of the S1 subunit, which contains the receptor-binding domain (RBD) and the N-terminal domain (NTD), and the S2 subunit, which mediates the fusion of viral and cellular membranes (Huang et al., 2020, Acta Pharm Sin). While the RBD is the primary target for most neutralizing antibodies, the S2 subunit and non-RBD regions like the NTD are highly conserved across variants, making them attractive targets for broad-spectrum therapeutics (Xia et al., 2020, Cell Res). The S2 subunit contains key functional elements, including the fusion peptide and heptad repeats (HR1 and HR2), which undergo a dramatic conformational change to form a six-helix bundle during the fusion process (V'kovski et al., 2021, Nat Rev Microbiol). Therapeutic interventions targeting these regions include fusion-inhibiting peptides like EK1, small molecules like Umifenovir, and various monoclonal antibodies and vaccines designed to elicit a robust immune response against conserved viral epitopes (Chi et al., 2020, Science; Pinto et al., 2021, Science).

Other names

Spike glycoproteinS proteinSurface glycoproteinS2 subunitFusion proteinNon-RBD spike regionsSARS-CoV-2 S2SARS-CoV-2 NTD

Inhibition of viral-host membrane fusion by blocking the S2 subunit conformational change or neutralizing viral entry through non-RBD epitopes.