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6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
Caleb D. Swaim; Yi-Chieh Perng; Xu Zhao; Larissa A. Canadeo; Houda H. Harastani; Tamarand L. Darling; Adrianus C. M. Boon; Deborah J. Lenschow; Jon M. Huibregtse.
Affiliation
  • Caleb D. Swaim; University of Texas Austin
  • Yi-Chieh Perng; Washington University School of Medicine
  • Xu Zhao; University of Texas at Austin
  • Larissa A. Canadeo; University of Texas at Austin
  • Houda H. Harastani; Washington University School of Medicine
  • Tamarand L. Darling; Washington University School of Medicine
  • Adrianus C. M. Boon; Washington University School of Medicine
  • Deborah J. Lenschow; Washington University School of Medicine
  • Jon M. Huibregtse; University of Texas at Austin
Preprint in English | bioRxiv | ID: ppbiorxiv-183020
Journal article
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ABSTRACT
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.One Sentence Summary A repurposed drug that targets an essential enzymatic activity of SARS-CoV-2 represents a promising COVID-19 therapeutic.Competing Interest StatementThe authors have declared no competing interest.View Full Text
License
cc_by_nc_nd
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint
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