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A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants

Author

Listed:
  • Yanyun Du

    (Huazhong University of Science and Technology)

  • Rui Shi

    (Chinese Academy of Sciences)

  • Ying Zhang

    (Peking University)

  • Xiaomin Duan

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

  • Li Li

    (Shanghai Junshi Biosciences Co., Ltd)

  • Jing Zhang

    (Shanghai Junshi Biosciences Co., Ltd)

  • Fengze Wang

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

  • Ruixue Zhang

    (Peking University)

  • Hao Shen

    (Peking University)

  • Yue Wang

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

  • Zheng Wu

    (Chinese Academy of Sciences
    Anhui University)

  • Qianwen Peng

    (Huazhong University of Science and Technology)

  • Ting Pan

    (Huazhong University of Science and Technology)

  • Wanwei Sun

    (Huazhong University of Science and Technology)

  • Weijin Huang

    (National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals)

  • Yue Feng

    (Beijing University of Chemical Technology)

  • Hui Feng

    (Shanghai Junshi Biosciences Co., Ltd)

  • Junyu Xiao

    (Peking University)

  • Wenjie Tan

    (Chinese Center for Disease Control and Prevention)

  • Youchun Wang

    (National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals)

  • Chenhui Wang

    (Huazhong University of Science and Technology)

  • Jinghua Yan

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

Abstract

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.

Suggested Citation

  • Yanyun Du & Rui Shi & Ying Zhang & Xiaomin Duan & Li Li & Jing Zhang & Fengze Wang & Ruixue Zhang & Hao Shen & Yue Wang & Zheng Wu & Qianwen Peng & Ting Pan & Wanwei Sun & Weijin Huang & Yue Feng & Hu, 2021. "A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25331-x
    DOI: 10.1038/s41467-021-25331-x
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    Cited by:

    1. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Zhenzhen Wang & Shiqi Hu & Kristen D. Popowski & Shuo Liu & Dashuai Zhu & Xuan Mei & Junlang Li & Yilan Hu & Phuong-Uyen C. Dinh & Xiaojie Wang & Ke Cheng, 2024. "Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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