SARS-CoV-2 spike protein S2 subunit and non-receptor binding domain epitopes (SARS-CoV-2 S2 and non-RBD epitopes)

The SARS-CoV-2 spike (S) protein is a large type I transmembrane glycoprotein that mediates viral entry into host cells (Huang et al., 2020, Signal Transduction and Targeted Therapy). It consists of two functional subunits: S1, which contains the receptor-binding domain (RBD) and the N-terminal domain (NTD), and S2, which contains the fusion machinery (Walls et al., 2020, Cell). While the RBD is the primary target for most neutralizing antibodies, the S2 subunit and non-RBD epitopes like the NTD are critical targets for developing broadly neutralizing therapies due to their higher conservation across variants (Shah et al., 2021, Nature Communications). The S2 subunit facilitates the fusion of the viral envelope with the host cell membrane through a dramatic conformational change involving the fusion peptide and heptad repeats (V'kovski et al., 2021, Nature Reviews Microbiology). Antibodies targeting non-RBD epitopes, such as the NTD, can neutralize the virus by inhibiting attachment to auxiliary receptors or interfering with the transition from pre-fusion to post-fusion states (McCallum et al., 2021, Science). These regions are central to the design of next-generation universal vaccines aimed at providing protection against a wide range of sarbecoviruses and emerging SARS-CoV-2 variants (Wang et al., 2022, Nature).

Other names

Spike S2 subunitNon-RBD spike epitopesSARS-CoV-2 S2N-terminal domain (NTD) epitopesFusion protein subunitSARS-CoV-2 S2 subunitSpike protein S2 subunit

Inhibition of viral-host membrane fusion by targeting the S2 subunit and neutralization of viral entry by binding to non-RBD epitopes such as the N-terminal domain (NTD).