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

Autor:	Swaim CD; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX., Perng YC; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Zhao X; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX., Canadeo LA; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX., Harastani HH; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Darling TL; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Boon ACM; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO., Lenschow DJ; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Huibregtse JM; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2020 Jul 02. Date of Electronic Publication: 2020 Jul 02.
DOI:	10.1101/2020.07.01.183020
Abstrakt:	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.
Databáze:	MEDLINE
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