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

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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SUBMITTER: Yang X

PROVIDER: S-EPMC8750650 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Yang Xuan X Dickmander Rebekah J RJ Bayati Armin A Taft-Benz Sharon A SA Smith Jeffery L JL Wells Carrow I CI Madden Emily A EA Brown Jason W JW Lenarcic Erik M EM Yount Boyd L BL Chang Edcon E Axtman Alison D AD Baric Ralph S RS Heise Mark T MT McPherson Peter S PS Moorman Nathaniel J NJ Willson Timothy M TM

bioRxiv : the preprint server for biology 20220126

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 wa ...[more]

PMID: 35018375

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