{"doi":"10.1101/2020.07.01.183020","title":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":118888,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":317859,"name":"Yi-Chieh Perng","orcid":"0000-0001-6996-0155","position":1,"is_corresponding":false},{"id":552348,"name":"Xu Zhao","orcid":"0000-0002-2477-8023","position":2,"is_corresponding":false},{"id":276313,"name":"Larissa A. Canadeo","orcid":null,"position":3,"is_corresponding":false},{"id":334925,"name":"Houda Harastani","orcid":"0000-0002-1234-6194","position":4,"is_corresponding":false},{"id":502614,"name":"Tamarand L. Darling","orcid":"0000-0001-6640-9165","position":5,"is_corresponding":false},{"id":334926,"name":"Adrianus C. M. Boon","orcid":"0000-0002-4700-8224","position":6,"is_corresponding":false},{"id":274234,"name":"Deborah J. Lenschow","orcid":"0000-0002-9400-5309","position":7,"is_corresponding":false},{"id":274235,"name":"Jon M. Huibregtse","orcid":"0000-0002-9210-3343","position":8,"is_corresponding":false},{"id":274232,"name":"Caleb D. Swaim","orcid":"0000-0003-4900-4515","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-18T23:14:03.409507Z","pmid":"32637945","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}