SARS-CoV-2 spike protein non-receptor binding domain surface epitopes (SARS-CoV-2 non-RBD epitopes)

The SARS-CoV-2 spike protein non-receptor binding domain (non-RBD) surface epitopes represent critical antigenic sites located on the N-terminal domain (NTD) and the S2 subunit of the viral spike glycoprotein. While the receptor-binding domain (RBD) is the primary target for many neutralizing antibodies, non-RBD epitopes play vital roles in viral attachment, conformational transitions, and membrane fusion (Walls et al., 2020, Cell). The NTD, for instance, contains a neutralizing supersite targeted by potent antibodies that can inhibit viral entry by interfering with auxiliary receptor interactions or stabilizing the pre-fusion state (McCallum et al., 2021, Science). The S2 subunit, containing the fusion peptide and heptad repeats, is highly conserved across coronaviruses, making its epitopes attractive targets for universal coronavirus vaccines and broad-spectrum therapeutics (Shah et al., 2021, Nature Communications). Targeting these regions is essential for overcoming the high mutation rates observed in the RBD of emerging variants of concern. Therapeutic strategies involving non-RBD epitopes often utilize monoclonal antibodies or structure-based vaccine design to elicit a more robust and variant-resistant immune response (Pinto et al., 2021, Science).

Other names

SARS-CoV-2 N-terminal domain (NTD)SARS-CoV-2 S2 subunitSpike protein stem regionFusion peptide (FP)Heptad repeat 1 (HR1)Heptad repeat 2 (HR2)SARS-CoV-2 S protein non-RBD regions

Neutralization of viral infection by inhibiting N-terminal domain-mediated attachment or S2-mediated membrane fusion, and induction of Fc-mediated effector functions.