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

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is a large, trimeric class I fusion glycoprotein that decorates the surface of the virus and is the primary mediator of host cell entry (UniProt P0DTC2). It consists of two functional subunits: S1, which contains the receptor-binding domain (RBD) that attaches to the human angiotensin-converting enzyme 2 (ACE2) receptor, and S2, which facilitates the fusion of the viral and cellular membranes (NCBI, 2020). As the most prominent surface antigen, the spike protein is the central target for the development of COVID-19 vaccines and therapeutic monoclonal antibodies (Nature Reviews Immunology, 2021). Mutations within the spike protein, particularly in the RBD and N-terminal domain, characterize various variants of concern (VOCs) like Delta and Omicron, which can lead to increased viral transmissibility and evasion of the host immune system (WHO, 2023). Therapeutic strategies focus on neutralizing the protein's ability to bind to ACE2 or preventing the conformational changes required for membrane fusion. Monitoring the evolution of spike protein variants is essential for maintaining the efficacy of current medical countermeasures and guiding the development of next-generation bivalent or universal vaccines.

Other names

Spike glycoproteinS proteinSurface glycoproteinSARS-CoV-2 SPeplomer protein

Vaccines induce the host to produce the spike protein, triggering an immune response that generates neutralizing antibodies and T-cells (CDC, 2021). Monoclonal antibodies bind to specific epitopes on the spike protein, primarily the receptor-binding domain (RBD), to sterically hinder the interaction with the host ACE2 receptor, thereby preventing viral attachment and entry (Nature, 2022).