SARS-CoV-2 spike glycoprotein (prefusion-stabilized) (SARS-CoV-2 S protein)

The SARS-CoV-2 spike (S) glycoprotein is a large trimeric class I fusion protein that mediates viral entry into host cells by binding to the human angiotensin-converting enzyme 2 (ACE2) receptor (Wrapp et al., 2020, Science). It is composed of two functional subunits: S1, which contains the receptor-binding domain (RBD), and S2, which facilitates the fusion of the viral and host cell membranes (UniProt P0DTC2). The prefusion-stabilized soluble trimeric ectodomain is an engineered version of the protein, often containing proline substitutions (e.g., K986P and V987P) to maintain the protein in its highly immunogenic prefusion state and a deleted transmembrane domain to ensure solubility (Pallesen et al., 2017, PNAS). This stabilized form is the primary antigen used in most COVID-19 vaccines, including mRNA-1273 and BNT162b2, to elicit a robust neutralizing antibody response (Corbett et al., 2020, Nature). Additionally, it serves as the target for numerous monoclonal antibodies designed to block viral attachment and entry, making it the central focus of therapeutic and prophylactic strategies against COVID-19 (Hansen et al., 2020, Science).

Other names

SARS-CoV-2 S-2PSpike proteinS proteinSARS-CoV-2 S-6PHexaProSpike ectodomain2019-nCoV spike protein

Drugs targeting this molecule, such as monoclonal antibodies and vaccine-induced antibodies, primarily act by binding to the receptor-binding domain (RBD) or the N-terminal domain (NTD) to sterically hinder the interaction with the host ACE2 receptor, or by binding to the S2 subunit to prevent the structural rearrangement necessary for membrane fusion (Kyriakidis et al., 2021, npj Vaccines).