{"doi":"10.21203/rs.3.rs-26344/v1","title":"Broad-spectrum inhibition of coronavirus main and papain-like proteases by HCV drugs","abstract":"<title>Abstract</title> Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has led to over 200,000 deaths thus far. We screened a library of approved antiviral drugs against the two SARS-CoV-2 proteases, 3C-like/main protease (3CLpro/Mpro) and papain-like protease (PLpro), which are essential for viral replication and attractive drug targets. Three HCV protease inhibitors were tested and found to inhibit 3CLpro and PLpro enzymes from Alpha-, Beta- and Gamma-coronaviruses. Anti-HIV drugs had no activity. Boceprevir and telaprevir inhibited 3CLpro, with boceprevir inhibiting eight of nine coronavirus 3CLpro enzymes tested including from SARS-CoV-2, MERS and SARS-CoV. Asunaprevir inhibited PLpro from SARS-CoV-2 and four other coronaviruses. The 1.4 Å X-ray structure of boceprevir bound to 3CLpro was determined to explain its broad-spectrum activity and guide structure-based design of inhibitors of multiple coronaviruses.Authors Brandon J. Anson, Mackenzie E. Chapman, and Emma K. Lendy contributed equally to this work.","journal":"Research Square (Research Square)","year":2020,"id":118759,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"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":107926,"name":"Mackenzie E. Chapman","orcid":"0000-0001-9969-2446","position":1,"is_corresponding":false},{"id":107927,"name":"Emma K. Lendy","orcid":"0000-0003-0619-8743","position":2,"is_corresponding":false},{"id":553120,"name":"S. Pshenychnyi","orcid":null,"position":3,"is_corresponding":false},{"id":329248,"name":"Richard T. D’Aquila","orcid":"0000-0002-9653-5987","position":4,"is_corresponding":false},{"id":36778,"name":"Karla J. F. Satchell","orcid":"0000-0003-3274-7611","position":5,"is_corresponding":false},{"id":107929,"name":"Andrew D. Mesecar","orcid":"0000-0002-1241-2577","position":6,"is_corresponding":false},{"id":550153,"name":"Brandon J. Anson","orcid":"0000-0003-2670-974X","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:03.409507Z","pmid":null,"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":[]}