{"doi":"10.1101/2020.08.28.271957","title":"Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2","abstract":"Abstract A consensus virtual screening protocol has been applied to ca. 2000 approved drugs to seek inhibitors of the main protease (M pro ) of SARS-CoV-2, the virus responsible for COVID-19. 42 drugs emerged as top candidates, and after visual analyses of the predicted structures of their complexes with M pro , 17 were chosen for evaluation in a kinetic assay for M pro inhibition. Remarkably 14 of the compounds at 100-μM concentration were found to reduce the enzymatic activity and 5 provided IC 50 values below 40 μM: manidipine (4.8 μM), boceprevir (5.4 μM), lercanidipine (16.2 μM), bedaquiline (18.7 μM), and efonidipine (38.5 μM). Structural analyses reveal a common cloverleaf pattern for the binding of the active compounds to the P1, P1’, and P2 pockets of M pro . Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119070,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9406,"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":552842,"name":"Julian Tirado‐Rives","orcid":"0000-0001-7330-189X","position":1,"is_corresponding":false},{"id":552843,"name":"M.G. Deshmukh","orcid":"0000-0002-3704-3229","position":2,"is_corresponding":false},{"id":426682,"name":"Joseph A. Ippolito","orcid":"0000-0002-9211-5766","position":3,"is_corresponding":false},{"id":552844,"name":"Chunhui Zhang","orcid":"0000-0002-4579-9202","position":4,"is_corresponding":false},{"id":552845,"name":"Israel Cabeza de Vaca","orcid":"0000-0002-6208-1091","position":5,"is_corresponding":false},{"id":500264,"name":"Maria-Elena Liosi","orcid":null,"position":6,"is_corresponding":false},{"id":368807,"name":"Karen S. Anderson","orcid":"0000-0003-3433-0780","position":7,"is_corresponding":false},{"id":368808,"name":"William L. Jorgensen","orcid":"0000-0002-3993-9520","position":8,"is_corresponding":false},{"id":552841,"name":"Mohammad Mehdi Ghahremanpour","orcid":"0000-0002-1129-6041","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T23:14:03.409507Z","pmid":"32869018","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":[]}