A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation

  1. Sisi Kang
  2. Mei Yang
  3. Suhua He
  4. Yueming Wang
  5. Xiaoxue Chen
  6. Yao-Qing Chen
  7. Zhongsi Hong
  8. Jing Liu
  9. Guanmin Jiang
  10. Qiuyue Chen
  11. Ziliang Zhou
  12. Zhechong Zhou
  13. Zhaoxia Huang
  14. Xi Huang
  15. Huanhuan He
  16. Weihong Zheng
  17. Hua-Xin Liao
  18. Fei Xiao
  19. Hong Shan
  20. Shoudeng Chen

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Abstract

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

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  1. Version published to 10.1038/s41467-021-23036-9
  2. Version published to 10.21203/rs.3.rs-106760/v1 on Research Square
  3. ScreenIT

    SciScore for 10.1101/2020.09.10.292318: (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: Thank you for sharing your data.

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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  4. Version published to 10.1101/2020.09.10.292318v1 on bioRxiv