Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses

[Image: see text] 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 correlat...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236220/
https://www.ncbi.nlm.nih.gov/pubmed/35723434
http://dx.doi.org/10.1021/acschembio.2c00378
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author 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.
author_facet 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.
author_sort Yang, Xuan
collection PubMed
description [Image: see text] 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.
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spelling pubmed-92362202022-06-27 Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-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. ACS Chem Biol [Image: see text] 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. American Chemical Society 2022-06-19 2022-07-15 /pmc/articles/PMC9236220/ /pubmed/35723434 http://dx.doi.org/10.1021/acschembio.2c00378 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle 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.
Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses
title Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses
title_full Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses
title_fullStr Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses
title_full_unstemmed Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses
title_short Host Kinase CSNK2 is a Target for Inhibition of Pathogenic SARS-like β-Coronaviruses
title_sort host kinase csnk2 is a target for inhibition of pathogenic sars-like β-coronaviruses
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236220/
https://www.ncbi.nlm.nih.gov/pubmed/35723434
http://dx.doi.org/10.1021/acschembio.2c00378
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