ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker

  1. Yuning Chen
  2. Ya-Nan Zhang
  3. Renhong Yan
  4. Guifeng Wang
  5. Yuanyuan Zhang
  6. Zhe-Rui Zhang
  7. Yaning Li
  8. Jianxia Ou
  9. Wendi Chu
  10. Zhijuan Liang
  11. Yongmei Wang
  12. Yi-Li Chen
  13. Ganjun Chen
  14. Qi Wang
  15. Qiang Zhou
  16. Bo Zhang
  17. Chunhe Wang

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Abstract

The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 “knock-in” mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and “alanine walk” studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and “broad-spectrum” management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.

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  1. Version published to 10.1038/s41392-021-00740-y
  2. Version published to 10.1101/2020.11.11.375972v2 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.11.11.375972: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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    • No protocol registration statement was detected.

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  4. Version published to 10.1101/2020.11.11.375972v1 on bioRxiv