SARS-CoV-2 Omicron spike glycoprotein (S protein) (S protein)

The SARS-CoV-2 Omicron spike (S) glycoprotein is a large, trimeric class I transmembrane fusion protein that decorates the surface of the Omicron variant of the virus [1.1.3, 1.5.1]. It is composed of two functional subunits: S1, which mediates attachment to the host cell via the receptor-binding domain (RBD) interacting with angiotensin-converting enzyme 2 (ACE2), and S2, which facilitates the fusion of viral and host cell membranes [1.1.2, 1.4.2]. The Omicron variant is distinguished by an exceptionally high number of mutations within the spike protein, particularly concentrated in the RBD and N-terminal domain (NTD), which enhance its binding affinity for ACE2 and enable profound evasion of neutralizing antibodies elicited by prior infection or early-generation vaccines [1.1.3, 1.3.3]. As the primary target for both the host immune response and therapeutic interventions, the spike protein is the central component of mRNA and protein-subunit vaccines and the target for monoclonal antibody therapies [1.1.4, 1.4.4]. However, the continuous evolution of Omicron into numerous sublineages has created a significant therapeutic challenge, as many previously effective monoclonal antibodies have lost their neutralizing activity, necessitating the ongoing development of variant-adapted vaccines and broadly neutralizing therapeutic agents [1.3.2, 1.5.2]. The protein's extensive N-linked glycosylation further serves as a glycan shield, masking conserved epitopes from immune recognition [1.2.4, 1.5.4]. Therapeutic strategies primarily focus on neutralizing the virus by blocking the RBD-ACE2 interaction or inhibiting the conformational changes required for membrane fusion [1.2.1, 1.4.1].

Other names

Spike proteinS proteinS glycoproteinPeplomer proteinE2Surface glycoproteinSARS-CoV-2 S protein

Neutralization of viral entry by binding to the receptor-binding domain (RBD) or N-terminal domain (NTD) of the spike protein, thereby sterically hindering the interaction with the host ACE2 receptor or preventing the conformational changes required for membrane fusion [1.2.1, 1.2.4, 1.4.4].