Middle East respiratory syndrome coronavirus spike glycoprotein S1 N-terminal domain (MERS-CoV S1-NTD)

The Middle East respiratory syndrome coronavirus spike glycoprotein S1 N-terminal domain (MERS-CoV S1-NTD) is a distinct structural region of the viral spike protein responsible for the initial stages of infection (UniProt A0A2R4KP93). While the receptor-binding domain (RBD) of the S1 subunit is the primary site for interaction with the host receptor dipeptidyl peptidase 4 (DPP4), the S1-NTD (also referred to as the S1A domain) functions as a secondary attachment factor by binding to sialoglycans on the host cell surface (NIH PMC6759331). This interaction is thought to facilitate viral concentration on the cell membrane and influence the virus's tissue tropism and host range (NIH PMC5457961). As a critical surface-exposed antigen, the S1-NTD is a key target for the development of neutralizing monoclonal antibodies and subunit vaccines (NIH PMC6759331). Experimental antibodies such as G2 and 5F9 have demonstrated the ability to neutralize MERS-CoV by blocking sialoglycan binding or by inducing conformational changes that prevent viral-host membrane fusion (NIH PMC6759331). However, the high rate of viral mutation and the potential for antibody-dependent enhancement (ADE) present significant challenges for the clinical development of S1-NTD-targeted therapies (NIH PMC5457961).

Other names

S1-NTDS1A domainSpike protein S1 subunit N-terminal domainMERS-CoV S1A

Neutralization of viral entry by blocking attachment to host cells or interfering with spike protein conformational changes.