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

The N-terminal domain (NTD) is a critical structural component of the S1 subunit of the SARS-CoV and SARS-CoV-2 spike (S) proteins [3, 8]. While the adjacent receptor-binding domain (RBD) is responsible for direct binding to the angiotensin-converting enzyme 2 (ACE2) receptor, the NTD plays a vital role in initial viral attachment to host cells, often through interactions with sugar molecules like sialic acids or specific protein co-receptors [1, 4, 5]. It is a major target for the host immune system, containing a 'supersite' where many potent neutralizing antibodies bind to inhibit viral entry [9, 10]. Mutations in the NTD are frequently observed in emerging variants of concern, such as Omicron, contributing significantly to immune evasion and increased transmissibility [1, 12]. Therapeutic strategies targeting the NTD include monoclonal antibodies that can be used alone or in combination with RBD-targeting drugs to provide broader protection against viral escape [6, 11]. Understanding the NTD's structure and function is essential for developing next-generation vaccines and pan-coronavirus therapies [10, 13].

Other names

Spike NTDS1-NTDN-terminal domain of the spike glycoproteinS protein NTDS1 subunit N-terminal domain

Neutralization of viral entry by blocking the interaction between the N-terminal domain and host cell co-receptors (e.g., sialic acids, gangliosides) or by stabilizing the spike protein in a prefusion 'down' conformation to prevent membrane fusion [1, 4, 6, 10].