SARS-CoV-2 Omicron spike protein non-RBD epitopes (Omicron S non-RBD epitopes)

The SARS-CoV-2 Omicron spike protein non-RBD epitopes are antigenic regions on the spike (S) protein of the Omicron variant (B.1.1.529) that are distinct from the receptor-binding domain (RBD). These epitopes are located within the N-terminal domain (NTD) of the S1 subunit and various functional regions of the S2 subunit, such as the fusion peptide, heptad repeats (HR1 and HR2), and the stem helix (Cameroni et al., 2022; Nature). While the Omicron variant possesses numerous mutations in the RBD that allow it to evade many existing vaccines and monoclonal antibodies, the non-RBD regions—particularly the S2 subunit—remain relatively conserved across different SARS-CoV-2 lineages (Zhou et al., 2022; Science). These epitopes are critical for the viral infection process, as the NTD can facilitate initial attachment to host cells, while the S2 subunit mediates the fusion of the viral and host cell membranes (V'kovski et al., 2021; Nature Reviews Microbiology). Therapeutic strategies targeting these non-RBD sites involve the use of broadly neutralizing antibodies (bnAbs) that inhibit viral entry by preventing the conformational changes required for membrane fusion or by sterically blocking attachment (McCallum et al., 2021; Cell). Consequently, these epitopes are high-priority targets for the development of next-generation, variant-proof therapeutics and universal coronavirus vaccines.

Other names

Omicron S2 subunit epitopesOmicron N-terminal domain epitopesSARS-CoV-2 Omicron spike protein conserved epitopesOmicron S non-receptor binding domain epitopes

Inhibition of viral-host membrane fusion and blockade of N-terminal domain-mediated viral attachment.