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Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist circulating variants

Author

Listed:
  • Tingting Li

    (Xiamen University
    Xiamen University)

  • Wenhui Xue

    (Xiamen University
    Xiamen University)

  • Qingbing Zheng

    (Xiamen University
    Xiamen University)

  • Shuo Song

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Chuanlai Yang

    (Xiamen University
    Xiamen University)

  • Hualong Xiong

    (Xiamen University
    Xiamen University)

  • Sibo Zhang

    (Xiamen University
    Xiamen University)

  • Minqing Hong

    (Xiamen University
    Xiamen University)

  • Yali Zhang

    (Xiamen University
    Xiamen University)

  • Hai Yu

    (Xiamen University
    Xiamen University)

  • Yuyun Zhang

    (Xiamen University
    Xiamen University)

  • Hui Sun

    (Xiamen University
    Xiamen University)

  • Yang Huang

    (Xiamen University
    Xiamen University)

  • Tingting Deng

    (Xiamen University
    Xiamen University)

  • Xin Chi

    (Xiamen University
    Xiamen University)

  • Jinjin Li

    (Xiamen University
    Xiamen University)

  • Shaojuan Wang

    (Xiamen University
    Xiamen University)

  • Lizhi Zhou

    (Xiamen University
    Xiamen University)

  • Tingting Chen

    (Xiamen University
    Xiamen University)

  • Yingbin Wang

    (Xiamen University
    Xiamen University)

  • Tong Cheng

    (Xiamen University
    Xiamen University)

  • Tianying Zhang

    (Xiamen University
    Xiamen University)

  • Quan Yuan

    (Xiamen University
    Xiamen University)

  • Qinjian Zhao

    (Xiamen University
    Xiamen University)

  • Jun Zhang

    (Xiamen University
    Xiamen University)

  • Jason S. McLellan

    (The University of Texas at Austin)

  • Z. Hong Zhou

    (California NanoSystems Institute (CNSI), UCLA
    University of California, Los Angeles)

  • Zheng Zhang

    (Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital
    Southern University of Science and Technology)

  • Shaowei Li

    (Xiamen University
    Xiamen University)

  • Ying Gu

    (Xiamen University
    Xiamen University)

  • Ningshao Xia

    (Xiamen University
    Xiamen University
    Chinese Academy of Medical Sciences)

Abstract

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.

Suggested Citation

  • Tingting Li & Wenhui Xue & Qingbing Zheng & Shuo Song & Chuanlai Yang & Hualong Xiong & Sibo Zhang & Minqing Hong & Yali Zhang & Hai Yu & Yuyun Zhang & Hui Sun & Yang Huang & Tingting Deng & Xin Chi &, 2021. "Cross-neutralizing antibodies bind a SARS-CoV-2 cryptic site and resist circulating variants," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25997-3
    DOI: 10.1038/s41467-021-25997-3
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    Cited by:

    1. Yang Yang & Shiyu Niu & Chenguang Shen & Liuqing Yang & Shuo Song & Yun Peng & Yifan Xu & Liping Guo & Liang Shen & Zhonghui Liao & Jiexiang Liu & Shengjie Zhang & Yanxin Cui & Jiayin Chen & Si Chen &, 2024. "Longitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Mingxi Li & Yifei Ren & Zhen Qin Aw & Bo Chen & Ziqing Yang & Yuqing Lei & Lin Cheng & Qingtai Liang & Junxian Hong & Yiling Yang & Jing Chen & Yi Hao Wong & Jing Wei & Sisi Shan & Senyan Zhang & Jiwa, 2022. "Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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