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 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.
bioRxiv the preprint server for biology