Unknown

Dataset Information

0

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

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.

SUBMITTER: Swaim CD 

PROVIDER: S-EPMC7337375 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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

Swaim Caleb D CD   Perng Yi-Chieh YC   Zhao Xu X   Canadeo Larissa A LA   Harastani Houda H HH   Darling Tamarand L TL   Boon Adrianus C M ACM   Lenschow Deborah J DJ   Huibregtse Jon M JM  

bioRxiv : the preprint server for biology 20200702

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  ...[more]

Similar Datasets

Unknown 6-Thioguanine blocks SARS-CoV-2 replication by inhibition of PLpro.
| S-EPMC8487320 | biostudies-literature
Unknown Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2
| S-SCDT-EMBOJ-2020-106275 | biostudies-other
Unknown Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2.
| S-EPMC7461020 | biostudies-literature
Unknown Pharmacological inhibition of fatty acid synthesis blocks SARS-CoV-2 replication.
| S-EPMC8475461 | biostudies-literature
Unknown Mercapto-pyrimidines are reversible covalent inhibitors of the papain-like protease (PLpro) and inhibit SARS-CoV-2 (SCoV-2) replication.
| S-EPMC10259201 | biostudies-literature
Unknown Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication.
| S-EPMC7453019 | biostudies-literature
Unknown Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication.
| S-EPMC10470319 | biostudies-literature
Unknown Inhibition of the 3CL Protease and SARS-CoV-2 Replication by Dalcetrapib.
| S-EPMC8230949 | biostudies-literature
Unknown Ubiquitin variants potently inhibit SARS-CoV-2 PLpro and viral replication via a novel site distal to the protease active site.
| S-EPMC9822107 | biostudies-literature
Unknown Identification of SARS-CoV-2 Papain-like Protease (PLpro) Inhibitors Using Combined Computational Approach.
| S-EPMC8805381 | biostudies-literature