Sarbecovirus spike glycoprotein (S-glycoprotein or S-protein)

The Sarbecovirus spike glycoprotein is a large, trimeric class I fusion protein protruding from the viral envelope, characterized by its distinctive "club-" or "petal-" shaped architecture visible by electron microscopy[1]. It is essential for viral entry, mediating attachment to host cell receptors (notably ACE2 in SARS-CoV and SARS-CoV-2) via its N-terminal S1 subunit, followed by membrane fusion driven by the S2 subunit[1][3]. The spike protein is highly glycosylated and undergoes proteolytic cleavage at the S1/S2 and S2' sites, priming it for fusion. It exists in metastable prefusion and stable postfusion conformations, with dramatic structural rearrangements required for membrane fusion[1][3]. The spike protein is the primary target for neutralizing antibodies and a major focus of vaccine development efforts due to its critical role in infection and its exposure on the virion surface[1]. Its genetic and structural variability among sarbecoviruses influences host specificity, immune evasion, and therapeutic targeting[2].

Other names

Spike proteinSpike (S) glycoproteinE2 (formerly)SARS-CoV and SARS-CoV-2 spike glycoprotein (for specific viruses within the sarbecovirus subgenus)

Neutralizing antibodies block receptor binding or interfere with conformational changes required for fusion; Small molecules and peptides may stabilize the prefusion conformation, prevent cleavage, or block membrane fusion; ACE2 decoys compete with cellular ACE2 for spike binding, preventing viral entry