Severe acute respiratory syndrome coronavirus 2 Spike glycoprotein (SARS-CoV-2 S protein) (SARS-CoV-2 S protein)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein is a large, homotrimeric class I fusion protein that mediates viral entry into host cells (UniProt: P0DTC2). It consists of two functional subunits: S1, which contains the receptor-binding domain (RBD) for attachment to the host angiotensin-converting enzyme 2 (ACE2) receptor, and S2, which facilitates the fusion of viral and cellular membranes (PubMed: 32155444). The S protein is the primary target for the host immune system, and its specific epitopes—particularly those within the RBD and N-terminal domain (NTD)—are the binding sites for neutralizing antibodies (PubMed: 32511530). Most COVID-19 vaccines and monoclonal antibody therapies are designed to target these epitopes to prevent infection or reduce disease severity. However, the protein's high susceptibility to mutations leads to the emergence of variants of concern that can evade existing immunity by altering these critical epitope structures (PubMed: 33686383). Consequently, the S protein remains a central focus for ongoing drug development and public health monitoring.

Other names

Spike proteinS proteinSurface glycoproteinPeplomer proteinSARS-CoV-2 S1/S2 proteinSpike glycoprotein epitopes

Neutralization of viral entry by binding to specific epitopes on the S1 or S2 subunits, thereby blocking the interaction between the receptor-binding domain (RBD) and the host ACE2 receptor or preventing the conformational changes required for membrane fusion.