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

The SARS-CoV-2 spike protein S1 N-terminal domain (NTD) is a critical structural component of the viral spike (S) glycoprotein, located at the distal end of the S1 subunit [7, 11]. While the receptor-binding domain (RBD) is the primary site for interacting with the human ACE2 receptor, the NTD plays a vital role in initial viral attachment, potentially by binding to host cell surface glycans or sialic acids [1, 5, 13]. It also acts as an allosteric modulator of spike protein cleavage and fusion kinetics, facilitating efficient entry into host cells [4]. The NTD is a major target for the host immune response and contains a "neutralizing supersite" where several potent neutralizing antibodies bind [2, 11]. However, it is also a hotspot for mutations in variants of concern (VOCs), such as Delta and Omicron, which contribute to immune evasion and increased transmissibility [5, 8]. Therapeutic strategies targeting the NTD include monoclonal antibodies and next-generation vaccines designed to provide broader protection against evolving viral strains [1, 20].

Other names

S1-NTDSpike protein N-terminal domainA domainS1-A

Neutralization of viral entry by blocking attachment to host cell co-receptors and inhibiting allosteric transitions required for membrane fusion [1, 2, 11].