Spike glycoprotein (S) of SARS-CoV-2 (S protein)

The Spike glycoprotein (S) is a large trimeric class I viral fusion protein found on the surface of coronaviruses, including SARS-CoV‑2. It is composed of two functional subunits per protomer—S1, which contains a receptor-binding domain responsible for attachment to host cell receptors such as angiotensin-converting enzyme 2 (ACE2), and S2, which mediates membrane fusion between virus and host cell membranes. The full-length mature S protein consists of approximately 1273 amino acids in SARS-CoV‑2. The trimeric structure protrudes from the virion surface forming characteristic “spikes,” giving coronaviruses their crown-like appearance under electron microscopy. The S glycoprotein is heavily glycosylated and undergoes significant conformational changes during virus entry. It is essential for infectivity, pathogenesis, tissue tropism determination, and serves as both a major antigenic determinant recognized by neutralizing antibodies during natural infection/vaccination—and thus is central to most COVID‑19 vaccine strategies—as well as a direct therapeutic target for monoclonal antibodies. Mutations within this gene are associated with altered transmissibility or immune escape properties among emerging variants.[1][3][4][5]

Other names

Spike proteinS proteinSARS-CoV-2 spike glycoproteinCoronavirus spike proteinE2 (historical)CoV_S1 (domain symbol)

Blockade of ACE2 binding to prevent virus attachment and entry[1][4] Inhibition of conformational changes required for membrane fusion[8] Induction of neutralizing antibodies that target key epitopes on the RBD or other regions to prevent infection/reduce severity[4]