Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies

  1. Renhong Yan
  2. Ruoke Wang
  3. Bin Ju
  4. Jinfang Yu
  5. Yuanyuan Zhang
  6. Nan Liu
  7. Jia Wang
  8. Qi Zhang
  9. Peng Chen
  10. Bing Zhou
  11. Yaning Li
  12. Yaping Shen
  13. Shuyuan Zhang
  14. Long Tian
  15. Yingying Guo
  16. Lu Xia
  17. Xinyue Zhong
  18. Lin Cheng
  19. Xiangyang Ge
  20. Juanjuan Zhao
  21. Hong-Wei Wang
  22. Xinquan Wang
  23. Zheng Zhang
  24. Linqi Zhang
  25. Qiang Zhou

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Abstract

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the “up” conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.

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  1. Version published to 10.1038/s41422-021-00487-9
  2. ScreenIT

    SciScore for 10.1101/2020.10.13.336800: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    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.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.10.13.336800v1 on bioRxiv