Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies. Antibodies that target the N-terminal domain (NTD) of the MERS-CoV spike remain poorly characterized. Here, Zhou et al. report the structural and functional analysis of the NTD-targeting mAb 7D10 and show that it synergizes with antibodies targeting the receptor-binding domain against different MERS-CoV strains.
【저자키워드】 Virology, X-ray crystallography, 【초록키워드】 neutralizing antibody, Structure, antibody, neutralization, monoclonal antibody, spike glycoprotein, MERS-CoV, DPP4, Dipeptidyl peptidase 4, Region, RBD, NTD, experiment, epitope, Strains, Critical, mechanism, binding, mAb, N-terminal domain, Analysis, conformational change, Middle East, residue, cell entry, help, respiratory syndrome coronavirus, neutralization breadth, MOST, cellular receptor, viral cell, pre-fusion, Effect, synergistic, bind, inhibit, characterized, functional, dependent on, the receptor-binding domain, inhibiting, explain, mutagenesis experiment, RBD-targeting antibodies, 【제목키워드】 neutralization, spike glycoprotein, MERS-CoV, epitope, N-terminal domain,