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

The SARS-CoV-2 spike (S) glycoprotein is a class I fusion protein responsible for viral attachment and entry into host cells. While much therapeutic focus is on the receptor-binding domain (RBD), the N-terminal domain (NTD) and additional non-RBD epitopes, such as those in the S2 subunit, are vital for viral fitness and represent significant neutralizing targets [McCallum et al., 2021, Science]. The NTD contains an antigenic supersite where several potent monoclonal antibodies bind to inhibit viral entry, potentially by interfering with attachment to auxiliary receptors like L-SIGN/DC-SIGN or preventing the transition of the spike protein from a pre-fusion to a post-fusion state [Chi et al., 2020, Science]. Non-RBD epitopes in the S2 subunit are particularly valuable due to their high degree of conservation across different coronaviruses, making them targets for universal vaccine and therapy development [Huang et al., 2020, Science]. However, the NTD is also a hotspot for mutations in variants of concern, which can lead to significant immune evasion and reduced efficacy of certain monoclonal antibody treatments [Harvey et al., 2021, Nature Reviews Microbiology].

Other names

NTDS1-NTDSpike N-terminal domainS2 subunit epitopesNon-RBD neutralizing epitopesSpike protein N-terminal domain

Neutralization of viral infection by blocking attachment to host cell co-receptors or inhibiting the structural rearrangements of the spike protein required for membrane fusion.