Spike glycoprotein S (coronavirus S protein) (S protein)

The spike glycoprotein S is a large trimeric class I fusion protein found on the surface of all coronaviruses, including SARS-CoV-2, SARS-CoV, and MERS-CoV, where it mediates viral entry into host cells[1][4][5][7][8]. The S protein comprises two subunits: S1, which contains the receptor-binding domain (RBD) responsible for binding host cell receptors (such as ACE2), and S2, which contains the fusion peptide responsible for membrane fusion[1][4][7][8]. Cleavage by host proteases (furin, TMPRSS2, cathepsin L) activates the S protein for membrane fusion[2][4][7]. The spike protein is highly immunogenic and the main antigen targeted by neutralizing antibodies and most COVID-19 vaccines[1][3][6][7]. It is central to viral infectivity, species specificity, and pathogenicity and is a therapeutic and diagnostic target in coronavirus infection[1][6][7]. References from this answer include [1][2][3][4][5][6][7][8].

Other names

Spike proteinS glycoproteinProtein SE2 (historical name)SARS-CoV-2 spike protein (for the organism-specific case)Coronavirus spike protein

Neutralizing antibodies bind the receptor-binding domain (RBD) and block ACE2 interaction, preventing viral entry[1][7] Small-molecule inhibitors or peptides block protease cleavage/fusion steps[6][2] Soluble ACE2 decoys compete for S protein binding