Spike glycoprotein (viral) (S protein (or S glycoprotein))

The **Spike glycoprotein** (S protein) is a large, trimeric class I viral fusion protein found on the surface of coronaviruses, projecting from the viral envelope and forming the characteristic "crown" seen by electron microscopy[1][7]. It mediates two critical steps in infection: attachment of the virus to host cell receptors—commonly angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and SARS-CoV-2—and subsequent fusion of the viral and host cell membranes via substantial conformational changes in its S2 domain[1][3][4][5]. The spike protein has two main subunits: S1 (containing the receptor-binding domain, responsible for recognizing and binding host receptors), and S2 (responsible for membrane fusion). Cleavage by host proteases is required for function[2][5]. The spike protein is highly immunogenic, is the dominant target of neutralizing antibodies, and is the principal antigen used in all current COVID-19 vaccines[1][3][4]. Its surface-exposed, essential role and immunogenicity make it a key therapeutic target; monoclonal antibodies and vaccines mainly work by blocking its receptor-binding or fusion activity[3][4][7]. Variability or mutation of the spike can alter host range, immune escape, and therapeutic efficacy.

Other names

Spike proteinS proteinviral spike proteinspike glycoproteinS glycoproteinenvelope spike proteinE2 (historic, in coronaviruses)

Neutralizing antibodies block receptor binding domain (RBD) to prevent virus attachment and entry Fusion inhibitors block S2-mediated membrane fusion Vaccines induce protective immune responses targeting spike epitopes