机构：[1]The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center forBiological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084 Beijing, China[2]Key Laboratory ofMedical Virology, National Health and Family Planning Commission, National Institute for Viral Disease Control and Prevention, China CDC, 102206 Beijing,China[3]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University CancerHospital & Institute, 100142 Beijing, China[4]Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of InfectiousDiseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, 100084 Beijing, China[5]Collaborative Innovation Center for Biotherapy,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 610065 Chengdu, China四川大学华西医院
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.
基金：
National Key
Plan for Scientific Research and Development of China (grants 2016YFD0500307 and
2016YFD0500301), the National Natural Science Foundation of China (grants 31470751
and U1405228), and the National Major Project for Control and Prevention of Infectious
Disease in China (2016ZX10004001-003).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|1 区综合性期刊
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最新[2023]版：
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第一作者：
第一作者机构：[1]The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center forBiological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084 Beijing, China
共同第一作者：
通讯作者：
通讯机构：[1]The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center forBiological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, 100084 Beijing, China[5]Collaborative Innovation Center for Biotherapy,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 610065 Chengdu, China
推荐引用方式(GB/T 7714)：
Zhou Haixia,Chen Yingzhu,Zhang Shuyuan,et al.Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein.[J].Nature communications.2019,10(1):3068.doi:10.1038/s41467-019-10897-4.
APA：
Zhou Haixia,Chen Yingzhu,Zhang Shuyuan,Niu Peihua,Qin Kun...&Wang Xinquan.(2019).Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein..Nature communications,10,(1)
MLA：
Zhou Haixia,et al."Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein.".Nature communications 10..1(2019):3068
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