PT  - JOURNAL ARTICLE
AU  - Caleb D. Swaim
AU  - Yi-Chieh Perng
AU  - Xu Zhao
AU  - Larissa A. Canadeo
AU  - Houda H. Harastani
AU  - Tamarand L. Darling
AU  - Adrianus C. M. Boon
AU  - Deborah J. Lenschow
AU  - Jon M. Huibregtse
TI  - 6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro protease activities
AID  - 10.1101/2020.07.01.183020
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.01.183020
4099  - http://biorxiv.org/content/early/2020/07/02/2020.07.01.183020.short
4100  - http://biorxiv.org/content/early/2020/07/02/2020.07.01.183020.full
AB  - 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.