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Host kinase CSNK2 is a target for inhibition of pathogenic β-coronaviruses including SARS-CoV-2
Xuan Yang; Rebekah J Dickmander; Armin Bayati; Sharon A Taft-Benz; Jeffrey L Smith; Carrow I Wells; Emily A Madden; Jason W Brown; Erik M Lenarcic; Boyd L Yount Jr.; Edcon Chang; Alison D Axtman; Ralph S Baric; Mark T Heise; Peter S McPherson; Nathaniel J Moorman; Timothy M Willson.
Afiliação
  • Xuan Yang; University of North Carolina at Chapel Hill
  • Rebekah J Dickmander; University of North Carolina at Chapel Hill
  • Armin Bayati; Montreal Neurological Institute
  • Sharon A Taft-Benz; University of North Carolina at Chapel Hill
  • Jeffrey L Smith; University of North Carolina at Chapel Hill
  • Carrow I Wells; University of North Carolina at Chapel Hill
  • Emily A Madden; University of North Carolina at Chapel Hill
  • Jason W Brown; Takeda San Diego
  • Erik M Lenarcic; University of North Carolina at Chapel Hill
  • Boyd L Yount Jr.; University of North Carolina at Chapel Hill
  • Edcon Chang; Takeda San Diego
  • Alison D Axtman; University of North Carolina at Chapel Hill
  • Ralph S Baric; University of North Carolina at Chapel Hill
  • Mark T Heise; University of North Carolina at Chapel Hill
  • Peter S McPherson; Montreal Neurological Institute
  • Nathaniel J Moorman; University of North Carolina at Chapel Hill
  • Timothy M Willson; University of North Carolina at Chapel Hill
Preprint em En | PREPRINT-BIORXIV | ID: ppbiorxiv-474779
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
Licença
cc_by_nc
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Idioma: En Ano de publicação: 2022 Tipo de documento: Preprint
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-BIORXIV Idioma: En Ano de publicação: 2022 Tipo de documento: Preprint