Spike glycoprotein S2 subunit (S2 subunit)

The Spike glycoprotein S2 subunit is the membrane-anchored, C-terminal subunit of the coronavirus spike protein that mediates the critical step of viral and host cell membrane fusion, enabling viral genome entry into the host cell cytoplasm[1][3][7][8]. The full spike protein is cleaved into two subunits, with S1 functioning in receptor binding and S2 performing fusion. S2 contains the fusion peptide, two heptad repeat regions (HR1 and HR2), a transmembrane domain, and a cytoplasmic tail[1][3][5]. Upon receptor engagement and proteolytic activation (by host proteases such as furin or TMPRSS2), S2 undergoes dramatic structural rearrangements to bring viral and cellular membranes into proximity, forming a stable six-helix bundle that drives fusion[7][2][5]. The S protein, including the S2 subunit, is a major antigenic target for vaccines and antiviral drugs, although most neutralizing antibodies target the more variable S1/RBD region. However, the highly conserved and functionally essential nature of S2 has motivated efforts to design broadly effective fusion inhibitors and next-generation vaccines against this domain[1][3][8].

Other names

Spike S2 subunitS2Coronavirus spike protein S2 subunitSARS-CoV-2 S2 subunit

Inhibition of S2 conformational changes to block membrane fusion - Disruption of S2 domain heptad repeat (HR1/HR2) interactions - Protease inhibition to prevent S protein cleavage/activation