SARS-CoV-2 Spike protein N-terminal domain and S2 domain (NTD-S2)

The SARS-CoV-2 Spike protein N-terminal domain (NTD) and S2 domain are key structural elements of the viral spike glycoprotein that mediate host cell entry [1.2.1, 1.2.5]. The NTD, located within the S1 subunit, is involved in initial viral attachment to host cell surfaces, often through interactions with sugar moieties like sialic acids, and plays a role in the allosteric regulation of the receptor-binding domain (RBD) [1.1.1, 1.3.4]. The S2 domain contains the essential fusion machinery, including the fusion peptide and heptad repeat regions, which undergo dramatic conformational changes to merge the viral and host membranes [1.2.1, 1.5.3]. Because the S2 domain is more highly conserved than the RBD across different SARS-CoV-2 variants and other coronaviruses, it is a primary target for the development of universal vaccines and broad-spectrum fusion inhibitors [1.4.1, 1.4.5]. Therapeutic strategies targeting these domains include monoclonal antibodies that neutralize the virus by disrupting trimer stability or blocking attachment, as well as peptides that prevent the structural transitions required for membrane fusion [1.4.3, 1.6.1, 1.6.5].

Other names

S1-NTDS2 subunitSpike protein non-RBD domainsS1-N-terminal domainSARS-CoV-2 S2 domainSARS-CoV-2 NTD

Inhibition of viral-host membrane fusion, blockade of initial viral attachment, and disruption of spike trimer integrity.