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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
CSNK2A1 nanoBRET data added to Tables 1-3, Figure 3 updated, and text revised. Emily Madden and Carrow Wells added as a co-authors. Funding acknowledgement corrected.