{"doi":"10.1128/aac.01889-24","title":"Combating yellow fever virus with 7-deaza-7-fluoro-2′-C-methyladenosine","abstract":"ABSTRACT Yellow fever virus (YFV) is a deadly zoonotic flavivirus endemic in tropical/sub-tropical Africa and South America transmitted by mosquito vector ( Aedes aegypti ; Haemagogus leucocelaenus ) to humans and non-human primates. There are no approved antiviral agents for YFV. We previously identified 7-deaza-7-fluoro-2′-C-methyladenosine (DFA) with anti-YFV activity. Interestingly, DFA exhibits pan-activity in vitro against flaviviruses, such as dengue, Japanese encephalitis, Zika, and hepatitis C. This study aimed to expand DFA’s anti-flavivirus profile. DFA exhibited potent sub-micromolar anti-YFV activity in vitro against both the vaccine strain (YFV-17D) and a viscerotropic clinical YFV isolate (DakH1279) concomitantly with low cellular cytotoxicity and no notable mitochondrial toxicity. In vivo , efficacy was assessed against both YFV-17DD and a human clinical isolate in A129 and AG129 mouse flavivirus infection models, respectively. DFA significantly reduced virus replication in the livers of YFV-infected mice and the hallmarks of YFV-induced liver damage, including alanine transaminase levels and indocyanine green clearance. Collectively, this work identifies DFA as a potent YFV inhibitor and lays the groundwork for further therapeutic development as a YFV and, potentially, pan-flavivirus therapeutic.","journal":"Antimicrobial Agents and Chemotherapy","year":2025,"id":539238,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":375883,"name":"Vivian Vasconcelos Costa","orcid":"0000-0002-0175-642X","position":1,"is_corresponding":false},{"id":903183,"name":"Lauren N. 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