{"doi":"10.1101/2021.05.19.444875","title":"4’-Fluorouridine is a broad-spectrum orally efficacious antiviral blocking respiratory syncytial virus and SARS-CoV-2 replication","abstract":"Abstract The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and the elderly. We describe 4’-fluorouridine (4’-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and SARS-CoV-2 with high selectivity index in cells and well-differentiated human airway epithelia. Polymerase inhibition in in vitro RdRP assays established for RSV and SARS-CoV-2 revealed transcriptional pauses at positions i or i +3/4 post-incorporation. Once-daily oral treatment was highly efficacious at 5 mg/kg in RSV-infected mice or 20 mg/kg in ferrets infected with SARS-CoV-2 WA1/2020 or variant-of-concern (VoC) isolate CA/2020, initiated 24 or 12 hours after infection, respectively. These properties define 4’-FlU as a broad-spectrum candidate for the treatment of RSV, SARS-CoV-2 and related RNA virus infections. One-Sentence Summary 4’-Fluorouridine is an orally available ribonucleoside analog that efficiently treats RSV and SARS-CoV-2 infections in vivo .","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215419,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":810167,"name":"Carolin M. Lieber","orcid":"0000-0002-6845-2746","position":1,"is_corresponding":false},{"id":273308,"name":"Megha Aggarwal","orcid":"0000-0002-6989-9064","position":2,"is_corresponding":false},{"id":228960,"name":"Robert M. Cox","orcid":"0000-0003-0620-1674","position":3,"is_corresponding":false},{"id":228961,"name":"Josef D. Wolf","orcid":"0000-0003-2507-6944","position":4,"is_corresponding":false},{"id":810749,"name":"Jeong-Joong Yoon","orcid":null,"position":5,"is_corresponding":false},{"id":346936,"name":"Märt Toots","orcid":"0000-0002-5049-3400","position":6,"is_corresponding":false},{"id":2361,"name":"Chengjin Ye","orcid":"0000-0002-1934-9494","position":7,"is_corresponding":false},{"id":729928,"name":"Zachary M. Sticher","orcid":"0000-0002-7022-1410","position":8,"is_corresponding":false},{"id":552478,"name":"Alexander A. Kolykhalov","orcid":"0000-0002-3966-9540","position":9,"is_corresponding":false},{"id":2423,"name":"Luis Martínez‐Sobrido","orcid":"0000-0001-7084-0804","position":10,"is_corresponding":false},{"id":552476,"name":"Gregory R. Bluemling","orcid":"0000-0001-9138-7578","position":11,"is_corresponding":false},{"id":552477,"name":"Michael G. Natchus","orcid":"0000-0001-5132-2833","position":12,"is_corresponding":false},{"id":552479,"name":"George R. Painter","orcid":"0000-0002-9803-8095","position":13,"is_corresponding":false},{"id":228962,"name":"Richard K. Plemper","orcid":"0000-0003-2034-2107","position":14,"is_corresponding":false},{"id":576114,"name":"Julien Sourimant","orcid":"0000-0002-1660-1666","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-18T23:52:55.971300Z","pmid":"34031658","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":[]}