SARS-CoV-2 Spike surface protein (S protein)

The SARS-CoV-2 Spike (S) surface protein is a large, trimeric class I fusion glycoprotein that serves as the primary mediator of viral entry into host cells (UniProt P0DTC2). It consists of two functional subunits: the S1 subunit, which contains the receptor-binding domain (RBD) for attachment to the host angiotensin-converting enzyme 2 (ACE2) receptor, and the S2 subunit, which facilitates the fusion of viral and host cell membranes (NIH, PMID: 32155444). As the most prominent surface antigen, the Spike protein is the central target for nearly all COVID-19 vaccines and therapeutic monoclonal antibodies. These interventions work by eliciting or providing antibodies that neutralize the virus, primarily by blocking the RBD-ACE2 interaction or inhibiting the structural rearrangements necessary for membrane fusion (Nature, 2020). Beyond its role in viral entry, the Spike protein is a key driver of the disease's pathogenesis, capable of triggering pro-inflammatory signaling and causing endothelial damage through ACE2 downregulation and interaction with other host factors like Toll-like receptors (Frontiers, 2025; Salk Institute, 2021). The protein's high mutational plasticity allows the virus to evolve variants that can evade neutralizing immunity, necessitating the development of strategies that target multiple epitopes to maintain therapeutic efficacy (Nature, 2020; MDPI, 2025).

Other names

Spike glycoproteinSurface glycoproteinSARS-CoV-2 S protein2019-nCoV S proteinSpike protein

Neutralization of viral entry by blocking the interaction between the Spike protein's Receptor Binding Domain (RBD) and the host ACE2 receptor, or by inhibiting membrane fusion (NIH, PMID: 32142651; Frontiers, 2022).