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

X. Yang; R. J. Dickmander; A. Bayati; S. A. Taft-Benz; J. L. Smith; C. I. Wells; E. A. Madden; J. W. Brown; E. M. Lenarcic; B. L. Yount; E. Chang; A. D. Axtman; R. S. Baric; M. T. Heise; P. S. McPherson; N. J. Moorman; T. M. Willson

doi:10.1101/2022.01.03.474779

Cell BiologybioRxivJan 3, 2022

Preprint

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

X. Yang, R. J. Dickmander, A. Bayati, S. A. Taft-Benz, J. L. Smith, C. I. Wells, E. A. Madden, J. W. Brown, E. M. Lenarcic, B. L. Yount, E. Chang, A. D. Axtman, R. S. Baric, M. T. Heise, P. S. McPherson, N. J. Moorman, T. 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 and murine {beta}-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 {beta}-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-{beta}-coronavirus drugs. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=72 SRC="FIGDIR/small/474779v3_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@5d2799org.highwire.dtl.DTLVardef@1d2de35org.highwire.dtl.DTLVardef@fa852eorg.highwire.dtl.DTLVardef@13da300_HPS_FORMAT_FIGEXP M_FIG C_FIG

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