Coronavirus spike protein (S protein)

The coronavirus spike (S) protein is a large, type I transmembrane glycoprotein that forms the characteristic crown-like protrusions on the surface of the viral envelope (UniProt P0DTC2). It is the primary mediator of viral entry into host cells, consisting of two functional subunits: S1, which contains the receptor-binding domain (RBD) for attachment to host receptors such as Angiotensin-Converting Enzyme 2 (ACE2), and S2, which facilitates the fusion of viral and cellular membranes (NCBI PMC7112330). Because of its essential role in the viral life cycle and its high visibility to the immune system, the spike protein is the principal target for neutralizing antibodies and the primary antigen used in the development of vaccines like BNT162b2 and mRNA-1273 (Nature Reviews Immunology, 2020). Therapeutic monoclonal antibodies, such as Sotrovimab and Bebtelovimab, target specific epitopes within the RBD or N-terminal domain (NTD) to block receptor engagement or inhibit the structural transitions required for fusion (FDA, 2022). However, the high mutation rate of the virus, particularly within these epitope regions, poses a significant challenge for long-term efficacy, leading to the emergence of variants of concern (VOCs) that can evade existing immunity (PubMed 33603082). Understanding the structural landscape of these epitopes is critical for designing variant-proof therapeutics and broadly neutralizing vaccines.

Other names

Spike glycoproteinS proteinPeplomer proteinReceptor-binding domain (RBD)N-terminal domain (NTD)Coronavirus spike protein epitopes

Neutralization of viral particles by blocking the receptor-binding domain (RBD) interaction with host receptors (e.g., ACE2) or inhibiting the S2-mediated membrane fusion process.