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Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein

Author

Listed:
  • Haixia Zhou

    (Tsinghua University)

  • Yingzhu Chen

    (National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC
    Peking University Cancer Hospital & Institute)

  • Shuyuan Zhang

    (Tsinghua University)

  • Peihua Niu

    (National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC)

  • Kun Qin

    (National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC)

  • Wenxu Jia

    (Tsinghua University)

  • Baoying Huang

    (National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC)

  • Senyan Zhang

    (Tsinghua University)

  • Jun Lan

    (Tsinghua University)

  • Linqi Zhang

    (Tsinghua University)

  • Wenjie Tan

    (National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC)

  • Xinquan Wang

    (Tsinghua University
    Sichuan University)

Abstract

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.

Suggested Citation

  • Haixia Zhou & Yingzhu Chen & Shuyuan Zhang & Peihua Niu & Kun Qin & Wenxu Jia & Baoying Huang & Senyan Zhang & Jun Lan & Linqi Zhang & Wenjie Tan & Xinquan Wang, 2019. "Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10897-4
    DOI: 10.1038/s41467-019-10897-4
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