6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities

A recently emerged betacoronavirus, SARS-CoV-2, has led to a global health crisis that calls for the identification of effective therapeutics for COVID-19 disease. Coronavirus papain-like protease (PLpro) is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjug...

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Autores principales: Swaim, Caleb D., Perng, Yi-Chieh, Zhao, Xu, Canadeo, Larissa A., Harastani, Houda H., Darling, Tamarand L., Boon, Adrianus C. M., Lenschow, Deborah J., Huibregtse, Jon M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337375/
https://www.ncbi.nlm.nih.gov/pubmed/32637945
http://dx.doi.org/10.1101/2020.07.01.183020
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author Swaim, Caleb D.
Perng, Yi-Chieh
Zhao, Xu
Canadeo, Larissa A.
Harastani, Houda H.
Darling, Tamarand L.
Boon, Adrianus C. M.
Lenschow, Deborah J.
Huibregtse, Jon M.
author_facet Swaim, Caleb D.
Perng, Yi-Chieh
Zhao, Xu
Canadeo, Larissa A.
Harastani, Houda H.
Darling, Tamarand L.
Boon, Adrianus C. M.
Lenschow, Deborah J.
Huibregtse, Jon M.
author_sort Swaim, Caleb D.
collection PubMed
description A recently emerged betacoronavirus, SARS-CoV-2, has led to a global health crisis that calls for the identification of effective therapeutics for COVID-19 disease. Coronavirus papain-like protease (PLpro) is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG) inhibits SARS-CoV-2 PLpro-catalyzed viral polyprotein cleavage and ISG15 deconjugation in cells and inhibits replication of SARS-CoV-2 in Vero-E6 cells and Calu3 cells at submicromolar levels. As a well-characterized FDA-approved orally delivered drug, 6-TG represents a promising therapeutic for COVID-19 and other emerging coronaviruses.
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spelling pubmed-73373752020-07-07 6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities Swaim, Caleb D. Perng, Yi-Chieh Zhao, Xu Canadeo, Larissa A. Harastani, Houda H. Darling, Tamarand L. Boon, Adrianus C. M. Lenschow, Deborah J. Huibregtse, Jon M. bioRxiv Article A recently emerged betacoronavirus, SARS-CoV-2, has led to a global health crisis that calls for the identification of effective therapeutics for COVID-19 disease. Coronavirus papain-like protease (PLpro) is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG) inhibits SARS-CoV-2 PLpro-catalyzed viral polyprotein cleavage and ISG15 deconjugation in cells and inhibits replication of SARS-CoV-2 in Vero-E6 cells and Calu3 cells at submicromolar levels. As a well-characterized FDA-approved orally delivered drug, 6-TG represents a promising therapeutic for COVID-19 and other emerging coronaviruses. Cold Spring Harbor Laboratory 2020-07-02 /pmc/articles/PMC7337375/ /pubmed/32637945 http://dx.doi.org/10.1101/2020.07.01.183020 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Swaim, Caleb D.
Perng, Yi-Chieh
Zhao, Xu
Canadeo, Larissa A.
Harastani, Houda H.
Darling, Tamarand L.
Boon, Adrianus C. M.
Lenschow, Deborah J.
Huibregtse, Jon M.
6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
title 6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
title_full 6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
title_fullStr 6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
title_full_unstemmed 6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
title_short 6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
title_sort 6-thioguanine blocks sars-cov-2 replication by inhibition of plpro protease activities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337375/
https://www.ncbi.nlm.nih.gov/pubmed/32637945
http://dx.doi.org/10.1101/2020.07.01.183020
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