SARS-CoV-2 spike protein S1 subunit N-terminal domain (NTD) (SARS-CoV-2 S-NTD)

The SARS-CoV-2 spike (S) protein is a large type I transmembrane glycoprotein that mediates viral entry into host cells (Harvey et al., 2021, Nature Reviews Microbiology). It is composed of two functional subunits: S1, which is responsible for receptor binding, and S2, which facilitates membrane fusion. Within the S1 subunit, the N-terminal domain (NTD) and other non-receptor-binding domain (non-RBD) epitopes serve as critical targets for the host immune system (McCallum et al., 2021, Cell). The NTD is particularly important as it contains an "antigenic supersite" targeted by potent neutralizing antibodies, such as 4A8, which inhibit viral entry by interfering with attachment to co-receptors or preventing necessary conformational changes (Chi et al., 2020, Science; Cerutti et al., 2021, Cell Reports). Mutations in these regions are a hallmark of SARS-CoV-2 variants of concern, contributing significantly to immune evasion and reduced vaccine efficacy (Harvey et al., 2021, Nature Reviews Microbiology). Consequently, the NTD and non-RBD S1 epitopes are major focuses for the development of broadly neutralizing antibodies and next-generation vaccines.

Other names

NTDS1-NTDSpike N-terminal domainNon-RBD S1 epitopesS1 subunitSARS-CoV-2 S1 domain

Neutralization of viral entry by blocking co-receptor binding (e.g., AXL, L-SIGN) or preventing the conformational transitions of the spike protein required for S1/S2 cleavage and membrane fusion (Chi et al., 2020, Science; McCallum et al., 2021, Cell).