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Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like ß-Coronaviruses.
Yang, Xuan; Dickmander, Rebekah J; Bayati, Armin; Taft-Benz, Sharon A; Smith, Jeffery L; Wells, Carrow I; Madden, Emily A; Brown, Jason W; Lenarcic, Erik M; Yount, Boyd L; Chang, Edcon; Axtman, Alison D; Baric, Ralph S; Heise, Mark T; McPherson, Peter S; Moorman, Nathaniel J; Willson, Timothy M.
  • Yang X; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Dickmander RJ; Rapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, North Carolina 27599, United States.
  • Bayati A; Rapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, North Carolina 27599, United States.
  • Taft-Benz SA; Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Smith JL; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Wells CI; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Madden EA; Structural Genomics Consortium, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
  • Brown JW; Rapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, North Carolina 27599, United States.
  • Lenarcic EM; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Yount BL; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Chang E; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Axtman AD; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Baric RS; Takeda San Diego, San Diego, California 92121, United States.
  • Heise MT; Rapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, North Carolina 27599, United States.
  • McPherson PS; Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Moorman NJ; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Willson TM; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
ACS Chem Biol ; 17(7): 1937-1950, 2022 07 15.
Article in English | MEDLINE | ID: covidwho-2106315
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 ß-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 ß-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 ß-coronavirus drugs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Coronavirus Limits: Animals / Humans Language: English Journal: ACS Chem Biol Year: 2022 Document Type: Article Affiliation country: Acschembio.2c00378

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Coronavirus Limits: Animals / Humans Language: English Journal: ACS Chem Biol Year: 2022 Document Type: Article Affiliation country: Acschembio.2c00378