SARS-CoV-2 spike protein N-terminal domain and non-receptor binding domain epitopes (NTD and non-RBD epitopes)

The SARS-CoV-2 spike (S) protein is a class I fusion protein that mediates viral entry into host cells. While the receptor-binding domain (RBD) is the most prominent target for neutralizing antibodies, the N-terminal domain (NTD) and other non-RBD epitopes in the S1 and S2 subunits play critical roles in the infection process (Chi et al., 2020, Science). The NTD is involved in initial viral attachment and facilitates the conformational changes necessary for the RBD to bind the ACE2 receptor (McCallum et al., 2021, Cell). Non-RBD epitopes in the S2 subunit, such as the fusion peptide and stem helix, are highly conserved across various coronaviruses and are essential for the fusion of viral and host cell membranes (Pinto et al., 2021, Science). Targeting these regions is a major focus for developing broad-spectrum therapeutics and vaccines that remain effective against emerging variants (Harvey et al., 2021, Nature Reviews Microbiology). Monoclonal antibodies targeting these domains function by preventing viral attachment, inhibiting the transition to a fusion-competent state, or mediating immune clearance of infected cells.

Other names

N-terminal domainNTDS1-NTDS2 subunitFusion peptideStem helixHeptad repeat 1 (HR1)Heptad repeat 2 (HR2)Conserved spike epitopesNon-RBD antigenic sites

Neutralization of viral entry through inhibition of attachment, steric hindrance of receptor binding, or prevention of membrane fusion.