Host kinase CSNK2 is a target for inhibition of pathogenic β-coronaviruses including SARS-CoV-2

  1. Xuan Yang
  2. Rebekah J. Dickmander
  3. Armin Bayati
  4. Sharon A. Taft-Benz
  5. Jeffery L. Smith
  6. Carrow I. Wells
  7. Emily A. Madden
  8. Jason W. Brown
  9. Erik M. Lenarcic
  10. Boyd L. Yount
  11. Edcon Chang
  12. Alison D. Axtman
  13. Ralph S. Baric
  14. Mark T. Heise
  15. Peter S. McPherson
  16. Nathaniel J. Moorman
  17. Timothy M. Willson

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Abstract

Inhibition of the protein kinase CSNK2 with any of 30 specific and selective inhibitors representing different chemotypes, blocked replication of pathogenic human and murine β-coronaviruses. The potency of in-cell CSNK2A target engagement across the set of inhibitors correlated with antiviral activity and genetic knockdown confirmed the essential role of the CSNK2 holoenzyme in β-coronavirus replication. Spike protein uptake was blocked by CSNK2A inhibition, indicating that antiviral activity was due in part to a suppression of viral entry. CSNK2A inhibition may be a viable target for development of new broad spectrum anti-β-coronavirus drugs.

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  1. Version published to 10.1101/2022.01.03.474779v3 on bioRxiv
  2. Version published to 10.1101/2022.01.03.474779v2 on bioRxiv
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    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot 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.

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    • 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.

    Results from scite Reference Check: We found no unreliable references.

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  4. Version published to 10.1101/2022.01.03.474779v1 on bioRxiv