Severe acute respiratory syndrome coronavirus 2 Spike protein S2 subunit (S2) (S2)

The SARS-CoV-2 Spike protein S2 subunit is a class I viral fusion protein subunit responsible for mediating the fusion between the viral envelope and the host cell membrane (UniProt: P0DTC2). It contains several highly conserved functional elements, including the fusion peptide (FP), heptad repeats 1 and 2 (HR1 and HR2), and a transmembrane domain (PubMed: 32221306). Following the binding of the S1 subunit to the ACE2 receptor and subsequent proteolytic cleavage at the S2' site, the S2 subunit undergoes a dramatic conformational rearrangement to form a post-fusion six-helix bundle (6HB), which pulls the viral and host membranes together (Nature: 10.1038/s41586-020-2179-y). Because the S2 domain is significantly more conserved across various coronavirus strains than the S1 domain, it is a primary target for the development of broad-spectrum (pan-coronavirus) vaccines and fusion inhibitor therapies (Science: 10.1126/science.abj8322). Therapeutic agents like the EK1 peptide and its derivatives target the HR1 region to prevent the HR1-HR2 interaction, effectively blocking viral entry across multiple variants (Cell: 10.1016/j.cell.2020.03.031).

Other names

SARS-CoV-2 S2 domainSpike protein S2 subunitFusion subunitS2 subunitSARS-CoV-2 S2

Inhibition of viral-host membrane fusion by binding to the heptad repeat 1 (HR1) region or the stem helix, preventing the formation of the six-helix bundle (6HB) required for viral entry (Cell: 10.1016/j.cell.2020.03.031; Science: 10.1126/science.abj8322).