Spike glycoprotein (S) of Severe acute respiratory syndrome coronavirus (SARS-CoV) (Spike protein (S))

The spike glycoprotein is a trimeric class I viral fusion protein on the coronavirus envelope that mediates host cell entry by binding a host receptor via its S1 subunit and driving membrane fusion via its S2 subunit[1][2][9]. Each protomer is a type I membrane protein of approximately 1273 amino acids in SARS-CoV/SARS‑CoV‑2, with an N-terminal signal peptide, an S1 region containing the N-terminal domain and receptor-binding domain (RBD), and an S2 region containing the fusion peptide, heptad repeats HR1 and HR2, transmembrane segment, and cytoplasmic tail[2][5][9]. The spike is heavily N‑glycosylated and undergoes proteolytic cleavage at the S1/S2 boundary (often by furin if a site is present) and at the S2′ site to activate fusion[1][2][3]. In SARS-related coronaviruses, the RBD engages the host receptor angiotensin‑converting enzyme 2 (ACE2), with the RBD toggling between “down” (receptor-inaccessible) and “up” (receptor-accessible) conformations prior to binding[2][4][8]. Receptor engagement and proteolytic activation trigger large conformational changes in S2, including HR1–HR2 assembly into a six-helix bundle that drives apposition and fusion of viral and cellular membranes[1][4][5]. Because spike governs attachment, fusion, and is the principal target of neutralizing antibodies, it is a key therapeutic and vaccine target; interventions include RBD‑blocking antibodies, S2 fusion inhibitors targeting HR1/HR2, and strategies that modulate or inhibit host proteases required for spike activation[3][4][5][7][9].

Other names

Spike proteinS glycoproteinSpike (S)Coronavirus spike proteinSARS coronavirus spike proteinSARS-CoV spike protein

Block receptor binding by targeting the receptor-binding domain (RBD) to prevent spike interaction with ACE2 Neutralize virions by binding epitopes on S1/RBD or N-terminal domain (NTD) Inhibit membrane fusion by targeting S2 heptad repeats (HR1/HR2) to prevent six-helix bundle formation Block proteolytic activation at S1/S2 or S2′ sites indirectly via host protease inhibition (e.g., TMPRSS2) Stabilize prefusion conformations that are non-fusogenic