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A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2

Author

Listed:
  • Rui Shi

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Chao Shan

    (Chinese Academy of Sciences)

  • Xiaomin Duan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhihai Chen

    (Capital Medical University)

  • Peipei Liu

    (Chinese Center for Disease Control and Prevention)

  • Jinwen Song

    (National Clinical Research Center for Infectious Diseases)

  • Tao Song

    (Chinese Academy of Sciences
    Shanxi Academy of Advanced Research and Innovation
    Hebei Normal University of Science and Technology)

  • Xiaoshan Bi

    (Chinese Academy of Sciences
    Anhui University)

  • Chao Han

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Lianao Wu

    (Anhui University
    Chinese Academy of Sciences)

  • Ge Gao

    (Chinese Academy of Sciences)

  • Xue Hu

    (Chinese Academy of Sciences)

  • Yanan Zhang

    (Chinese Academy of Sciences)

  • Zhou Tong

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Weijin Huang

    (National Institutes for Food and Drug Control)

  • William Jun Liu

    (Chinese Center for Disease Control and Prevention)

  • Guizhen Wu

    (Chinese Center for Disease Control and Prevention)

  • Bo Zhang

    (Chinese Academy of Sciences)

  • Lan Wang

    (National Institutes for Food and Drug Control)

  • Jianxun Qi

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Hui Feng

    (Shanghai Junshi Biosciences Co. Ltd)

  • Fu-Sheng Wang

    (National Clinical Research Center for Infectious Diseases)

  • Qihui Wang

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • George Fu Gao

    (Chinese Academy of Sciences)

  • Zhiming Yuan

    (Chinese Academy of Sciences)

  • Jinghua Yan

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

An outbreak of coronavirus disease 2019 (COVID-19)1–3, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)4, has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus–receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.

Suggested Citation

  • Rui Shi & Chao Shan & Xiaomin Duan & Zhihai Chen & Peipei Liu & Jinwen Song & Tao Song & Xiaoshan Bi & Chao Han & Lianao Wu & Ge Gao & Xue Hu & Yanan Zhang & Zhou Tong & Weijin Huang & William Jun Liu, 2020. "A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2," Nature, Nature, vol. 584(7819), pages 120-124, August.
    • Handle: RePEc:nat:nature:v:584:y:2020:i:7819:d:10.1038_s41586-020-2381-y
    DOI: 10.1038/s41586-020-2381-y
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    Cited by:

    1. Zepeng Xu & Xinrui Kang & Pu Han & Pei Du & Linjie Li & Anqi Zheng & Chuxia Deng & Jianxun Qi & Xin Zhao & Qihui Wang & Kefang Liu & George Fu Gao, 2022. "Binding and structural basis of equine ACE2 to RBDs from SARS-CoV, SARS-CoV-2 and related coronaviruses," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Yifan Wang & Caixuan Liu & Chao Zhang & Yanxing Wang & Qin Hong & Shiqi Xu & Zuyang Li & Yong Yang & Zhong Huang & Yao Cong, 2022. "Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Pauline Maisonnasse & Yoann Aldon & Aurélien Marc & Romain Marlin & Nathalie Dereuddre-Bosquet & Natalia A. Kuzmina & Alec W. Freyn & Jonne L. Snitselaar & Antonio Gonçalves & Tom G. Caniels & Judith , 2021. "COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Wanbo Tai & Kai Yang & Yubin Liu & Ruofan Li & Shengyong Feng & Benjie Chai & Xinyu Zhuang & Shaolong Qi & Huicheng Shi & Zhida Liu & Jiaqi Lei & Enhao Ma & Weixiao Wang & Chongyu Tian & Ting Le & Jin, 2023. "A lung-selective delivery of mRNA encoding broadly neutralizing antibody against SARS-CoV-2 infection," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Emanuele Andreano & Ida Paciello & Giulio Pierleoni & Giuseppe Maccari & Giada Antonelli & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevra Giglioli & Giulia Piccini & Concetta De Santi &, 2023. "mRNA vaccines and hybrid immunity use different B cell germlines against Omicron BA.4 and BA.5," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    6. Yu Guo & Guangshun Zhang & Qi Yang & Xiaowei Xie & Yang Lu & Xuelian Cheng & Hui Wang & Jingxi Liang & Jielin Tang & Yuxin Gao & Hang Shang & Jun Dai & Yongxia Shi & Jiaxi Zhou & Jun Zhou & Hangtian G, 2023. "Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Didar Baimanov & Jing Wang & Jun Zhang & Ke Liu & Yalin Cong & Xiaomeng Shi & Xiaohui Zhang & Yufeng Li & Xiumin Li & Rongrong Qiao & Yuliang Zhao & Yunlong Zhou & Liming Wang & Chunying Chen, 2022. "In situ analysis of nanoparticle soft corona and dynamic evolution," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Monica Neagu & Carolina Constantin & Mihaela Surcel, 2021. "Testing Antigens, Antibodies, and Immune Cells in COVID-19 as a Public Health Topic—Experience and Outlines," IJERPH, MDPI, vol. 18(24), pages 1-16, December.
    9. Runchu Zhao & Lili Wu & Junqing Sun & Dezhi Liu & Pu Han & Yue Gao & Yi Zhang & Yanli Xu & Xiao Qu & Han Wang & Yan Chai & Zhihai Chen & George F. Gao & Qihui Wang, 2024. "Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    10. Tingting Li & Xiaojian Han & Chenjian Gu & Hangtian Guo & Huajun Zhang & Yingming Wang & Chao Hu & Kai Wang & Fengjiang Liu & Feiyang Luo & Yanan Zhang & Jie Hu & Wang Wang & Shenglong Li & Yanan Hao , 2021. "Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    11. Yanqun Wang & An Yan & Deyong Song & Maoqin Duan & Chuangchuang Dong & Jiantao Chen & Zihe Jiang & Yuanzhu Gao & Muding Rao & Jianxia Feng & Zhaoyong Zhang & Ruxi Qi & Xiaomin Ma & Hong Liu & Beibei Y, 2024. "Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    12. Andrew C. Hunt & Bastian Vögeli & Ahmed O. Hassan & Laura Guerrero & Weston Kightlinger & Danielle J. Yoesep & Antje Krüger & Madison DeWinter & Michael S. Diamond & Ashty S. Karim & Michael C. Jewett, 2023. "A rapid cell-free expression and screening platform for antibody discovery," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    13. Zhennan Zhao & Yufeng Xie & Bin Bai & Chunliang Luo & Jingya Zhou & Weiwei Li & Yumin Meng & Linjie Li & Dedong Li & Xiaomei Li & Xiaoxiong Li & Xiaoyun Wang & Junqing Sun & Zepeng Xu & Yeping Sun & W, 2023. "Structural basis for receptor binding and broader interspecies receptor recognition of currently circulating Omicron sub-variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Yingdan Wang & Aihua Hao & Ping Ji & Yunping Ma & Zhaoyong Zhang & Jiali Chen & Qiyu Mao & Xinyi Xiong & Palizhati Rehati & Yajie Wang & Yanqun Wang & Yumei Wen & Lu Lu & Zhenguo Chen & Jincun Zhao & , 2024. "A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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