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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