SARS-CoV-2 spike glycoprotein (ancestral strain, prefusion-stabilized) (SARS-CoV-2 S protein (2P))

The SARS-CoV-2 spike (S) glycoprotein is the primary surface protein of the virus responsible for mediating host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2) receptor (Wrapp et al., Science, 2020). In its ancestral form, derived from the Wuhan-Hu-1 strain, the protein is a homotrimer that undergoes significant conformational changes from a prefusion to a postfusion state during the infection process (UniProt P0DTC2). To enhance its stability and immunogenicity for vaccine development, researchers introduced two proline substitutions (K986P and V987P), known as the 2P mutation, which lock the protein in its prefusion state (Pallesen et al., PNAS, 2017). This stabilized version is the central component of major COVID-19 vaccines, including BNT162b2 and mRNA-1273, as it preserves the structural integrity of critical neutralizing epitopes (Corbett et al., Nature, 2020). Beyond vaccines, the spike protein is the target for numerous monoclonal antibodies designed to block viral attachment and entry (Polack et al., NEJM, 2020). However, the emergence of variants with mutations in the spike protein has posed significant challenges to the long-term efficacy of these ancestral-based therapeutics due to reduced neutralization sensitivity.

Other names

Spike proteinS protein2P-stabilized spikeWuhan-Hu-1 spike proteinSurface glycoproteinSARS-CoV-2 S-2P

Vaccines utilize the prefusion-stabilized spike protein as an antigen to induce neutralizing antibodies and cellular immune responses that prevent viral entry. Monoclonal antibodies bind to specific epitopes, primarily within the receptor-binding domain (RBD), to competitively inhibit binding to the host ACE2 receptor or to prevent the conformational changes required for membrane fusion.