{"doi":"10.3390/v16040651","title":"Why Certain Repurposed Drugs Are Unlikely to Be Effective Antivirals to Treat SARS-CoV-2 Infections","abstract":"Most repurposed drugs have proved ineffective for treating COVID-19. We evaluated median effective and toxic concentrations (EC50, CC50) of 49 drugs, mostly from previous clinical trials, in Vero cells. Ratios of reported unbound peak plasma concentrations, (Cmax)/EC50, were used to predict the potential in vivo efficacy. The 20 drugs with the highest ratios were retested in human Calu-3 and Caco-2 cells, and their CC50 was determined in an expanded panel of cell lines. Many of the 20 drugs with the highest ratios were inactive in human Calu-3 and Caco-2 cells. Antivirals effective in controlled clinical trials had unbound Cmax/EC50 ≥ 6.8 in Calu-3 or Caco-2 cells. EC50 of nucleoside analogs were cell dependent. This approach and earlier availability of more relevant cultures could have reduced the number of unwarranted clinical trials.","journal":"Viruses","year":2024,"id":463230,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":929758,"name":"Ramyani De","orcid":"0000-0001-5534-0705","position":1,"is_corresponding":false},{"id":693450,"name":"Julia C. LeCher","orcid":"0000-0002-0056-176X","position":2,"is_corresponding":false},{"id":314481,"name":"Jessica Downs-Bowen","orcid":"0000-0002-7472-033X","position":3,"is_corresponding":false},{"id":900941,"name":"Shu Ling Goh","orcid":"0000-0001-8575-6103","position":4,"is_corresponding":false},{"id":244969,"name":"Keivan Zandi","orcid":"0000-0001-9728-5038","position":5,"is_corresponding":false},{"id":315999,"name":"Tamara R. McBrayer","orcid":null,"position":6,"is_corresponding":false},{"id":314480,"name":"Franck Amblard","orcid":"0009-0002-6235-4050","position":7,"is_corresponding":false},{"id":432486,"name":"Dharmeshkumar Patel","orcid":"0000-0003-1601-256X","position":8,"is_corresponding":false},{"id":694293,"name":"James J. Kohler","orcid":null,"position":9,"is_corresponding":false},{"id":253631,"name":"Manoj Bhasin","orcid":"0000-0001-5172-420X","position":10,"is_corresponding":false},{"id":393270,"name":"Brian Dobosh","orcid":"0000-0003-1537-7188","position":11,"is_corresponding":false},{"id":718922,"name":"Vikas P. Sukhatme","orcid":"0000-0002-1825-6034","position":12,"is_corresponding":false},{"id":393272,"name":"Rabindra Tirouvanziam","orcid":"0000-0003-3526-9985","position":13,"is_corresponding":false},{"id":228075,"name":"Raymond F. Schinazi","orcid":"0000-0002-6688-3614","position":14,"is_corresponding":false},{"id":656258,"name":"Selwyn J. Hurwitz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":173,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:04:28.838123Z","pmid":"38675992","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":[]}