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A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes

Author

Listed:
  • Yu Guo

    (Nankai University)

  • Lisu Huang

    (Shanghai Jiao Tong University School of Medicine)

  • Guangshun Zhang

    (Nankai University
    Nankai University)

  • Yanfeng Yao

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • He Zhou

    (HiFiBio (Hong Kong) Limited)

  • Shu Shen

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Bingqing Shen

    (HiFiBio (Hong Kong) Limited)

  • Bo Li

    (Nankai University
    Nankai University)

  • Xin Li

    (Nankai University
    Nankai University)

  • Qian Zhang

    (HiFiBio (Hong Kong) Limited)

  • Mingjie Chen

    (HiFiBio (Hong Kong) Limited)

  • Da Chen

    (Nankai University
    Nankai University)

  • Jia Wu

    (HiFiBio (Hong Kong) Limited)

  • Dan Fu

    (Nankai University)

  • Xinxin Zeng

    (Shanghai Jiao Tong University School of Medicine)

  • Mingfang Feng

    (HiFiBio (Hong Kong) Limited)

  • Chunjiang Pi

    (HiFiBio (Hong Kong) Limited)

  • Yuan Wang

    (Nankai University
    Nankai University)

  • Xingdong Zhou

    (Nankai University
    Nankai University)

  • Minmin Lu

    (HiFiBio (Hong Kong) Limited)

  • Yarong Li

    (Wuxi Biologics Limited)

  • Yaohui Fang

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Yun-Yueh Lu

    (HiFiBio (Hong Kong) Limited)

  • Xue Hu

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Shanshan Wang

    (HiFiBio (Hong Kong) Limited)

  • Wanju Zhang

    (Shanghai Jiao Tong University School of Medicine)

  • Ge Gao

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Francisco Adrian

    (HiFiBio (Hong Kong) Limited)

  • Qisheng Wang

    (Shanghai Advanced Research Institute, Chinese Academy of Sciences)

  • Feng Yu

    (Shanghai Advanced Research Institute, Chinese Academy of Sciences)

  • Yun Peng

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Alexander G. Gabibov

    (Russian Academy of Sciences)

  • Juan Min

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Yuhui Wang

    (Nankai University
    Nankai University)

  • Heyu Huang

    (Shanghai Jiao Tong University School of Medicine)

  • Alexey Stepanov

    (Russian Academy of Sciences)

  • Wei Zhang

    (Nankai University
    Nankai University)

  • Yan Cai

    (Tianjin International Joint Academy of Biotechnology & Medicine)

  • Junwei Liu

    (Tianjin International Joint Academy of Biotechnology & Medicine)

  • Zhiming Yuan

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Chen Zhang

    (Nankai University)

  • Zhiyong Lou

    (Tsinghua University)

  • Fei Deng

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Hongkai Zhang

    (Nankai University
    Nankai University
    ShanghaiTech University
    Nankai University)

  • Chao Shan

    (Wuhan Institute of Virology, Chinese Academy of Sciences)

  • Liang Schweizer

    (HiFiBio (Hong Kong) Limited)

  • Kun Sun

    (Shanghai Jiao Tong University School of Medicine)

  • Zihe Rao

    (Nankai University
    Nankai University
    Nankai University
    Guangzhou Laboratory)

Abstract

COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.

Suggested Citation

  • Yu Guo & Lisu Huang & Guangshun Zhang & Yanfeng Yao & He Zhou & Shu Shen & Bingqing Shen & Bo Li & Xin Li & Qian Zhang & Mingjie Chen & Da Chen & Jia Wu & Dan Fu & Xinxin Zeng & Mingfang Feng & Chunji, 2021. "A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22926-2
    DOI: 10.1038/s41467-021-22926-2
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