Inhibition of amyloid formation of the Nucleoprotein of SARS-CoV-2

  1. Einav Tayeb-Fligelman
  2. Xinyi Cheng
  3. Christen Tai
  4. Jeannette T. Bowler
  5. Sarah Griner
  6. Michael R. Sawaya
  7. Paul M. Seidler
  8. Yi Xiao Jiang
  9. Jiahui Lu
  10. Gregory M. Rosenberg
  11. Lukasz Salwinski
  12. Romany Abskharon
  13. Chih-Te Zee
  14. Ke Hou
  15. Yan Li
  16. David R. Boyer
  17. Kevin A. Murray
  18. Genesis Falcon
  19. Daniel H. Anderson
  20. Duilio Cascio
  21. Lorena Saelices
  22. Robert Damoiseaux
  23. Feng Guo
  24. David S. Eisenberg

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Abstract

The SARS-CoV-2 Nucleoprotein (NCAP) functions in RNA packaging during viral replication and assembly. Computational analysis of its amino acid sequence reveals a central low-complexity domain (LCD) having sequence features akin to LCDs in other proteins known to function in liquid–liquid phase separation. Here we show that in the presence of viral RNA, NCAP, and also its LCD segment alone, form amyloid-like fibrils when undergoing liquid–liquid phase separation. Within the LCD we identified three 6-residue segments that drive amyloid fibril formation. We determined atomic structures for fibrils formed by each of the three identified segments. These structures informed our design of peptide inhibitors of NCAP fibril formation and liquid–liquid phase separation, suggesting a therapeutic route for Covid-19.

One Sentence Summary

Atomic structures of amyloid-driving peptide segments from SARS-CoV-2 Nucleoprotein inform the development of Covid-19 therapeutics.

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  1. Version published to 10.1101/2021.03.05.434000v2 on bioRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.03.05.434000: (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.
    • 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.

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  3. Version published to 10.1101/2021.03.05.434000v1 on bioRxiv