SARS-CoV-2 Omicron BA.1 spike glycoprotein (S protein (BA.1))

The SARS-CoV-2 Omicron BA.1 spike glycoprotein is a class I fusion protein that serves as the primary mediator of viral entry for the B.1.1.529 (Omicron) variant. It is composed of two subunits: S1, which contains the receptor-binding domain (RBD) for attachment to the human angiotensin-converting enzyme 2 (ACE2) receptor, and S2, which facilitates the fusion of the viral and host cell membranes (UniProt: P0DTC2; Mannar et al., Science 2022). The BA.1 lineage is characterized by an unprecedented number of mutations—over 30 in the spike protein alone—which significantly enhance its binding affinity for ACE2 while simultaneously allowing it to evade many neutralizing antibodies elicited by prior infection or original vaccine formulations (Cao et al., Nature 2022). This protein is the central target for COVID-19 vaccines and therapeutic monoclonal antibodies. However, the structural shifts in the BA.1 spike led to the loss of clinical efficacy for several major antibody treatments, such as the Casirivimab/Imdevimab cocktail, while others like Sotrovimab retained partial activity (FDA, 2022). Consequently, the BA.1 spike protein has been a critical focus for the development of bivalent mRNA vaccines and next-generation biologics designed to provide broader protection against evolving SARS-CoV-2 variants.

Other names

Omicron BA.1 spike proteinB.1.1.529 spike glycoproteinSARS-CoV-2 S protein (Omicron BA.1)Surface glycoprotein (SARS-CoV-2 Omicron BA.1)

Monoclonal antibodies and vaccine-elicited antibodies bind to specific epitopes on the S1 subunit (particularly the Receptor Binding Domain or RBD) or the N-terminal domain (NTD) of the spike protein. This binding sterically hinders the interaction between the spike protein and the human Angiotensin-Converting Enzyme 2 (ACE2) receptor, thereby neutralizing the virus and preventing its entry into host cells (Cameroni et al., Nature 2022; FDA, 2022).