Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses
Xuan Yang, Rebekah J. Dickmander, Armin Bayati, Sharon Taft-Benz, Jeffery L. Smith, Carrow I. Wells, Emily A. Madden, Jason W. Brown, Erik M. Lenarcic, Boyd L. Yount, Edcon Chang, Alison D. Axtman, Ralph S. Baric, Mark T. Heise, Peter S. McPherson, Nathaniel J. Moorman, Timothy M. Willson
Abstract
Inhibition of the protein kinase CSNK2 with any of 30 specific and selective inhibitors representing different chemotypes, blocked replication of pathogenic human, bat, 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 endocytosis 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 the development of anti-SARS-like β-coronavirus drugs.