Severe acute respiratory syndrome coronavirus 2 spike glycoprotein (S-2P) (SARS-CoV-2 S-2P)

The Severe acute respiratory syndrome coronavirus 2 spike glycoprotein (S-2P) is the primary surface protein of the SARS-CoV-2 virus and the critical mediator of viral entry into host cells (Wrapp et al., 2020, Science). It functions by binding the host Angiotensin-converting enzyme 2 (ACE2) receptor via its receptor-binding domain (RBD), followed by a conformational change that facilitates membrane fusion. The "S-2P" designation refers to a stabilized prefusion form of the protein created by substituting two consecutive residues (K986 and V987) with prolines, a modification that preserves the most immunogenic epitopes for vaccine development (Corbett et al., 2020, Nature). In the context of the immune system, this protein is the central antigen presented by Major Histocompatibility Complex (MHC) molecules to elicit neutralizing antibodies and cellular T-cell responses (Pardi et al., 2018, Nature Reviews Drug Discovery). Most authorized COVID-19 vaccines, including mRNA and protein subunit platforms, utilize the S-2P sequence to ensure high levels of protective immunity (Sahin et al., 2020, Nature). Additionally, the spike protein is the target for therapeutic monoclonal antibodies, which bind to the protein to neutralize the virus and prevent infection (Hansen et al., 2020, Science). Continuous monitoring of mutations within this protein is essential, as variants of concern can alter its structure and lead to immune evasion (Harvey et al., 2021, Nature Reviews Microbiology).

Other names

Spike proteinS proteinSARS-CoV-2 surface glycoproteinStabilized spike protein2P-stabilized S proteinSARS-CoV-2 S-2P spike protein

The S-2P protein acts as a stabilized antigen that is presented by Major Histocompatibility Complex (MHC) molecules to activate B-cells and T-cells, leading to the production of neutralizing antibodies and cellular immunity (Pardi et al., 2018, Nature Reviews Drug Discovery). Monoclonal antibodies bind directly to the spike protein's receptor-binding domain (RBD) to block its interaction with the host ACE2 receptor, thereby preventing viral entry (Hansen et al., 2020, Science).