| Title: |
Combating yellow fever virus with 7-deaza-7-fluoro-2′-C-methyladenosine |
| Authors: |
LeCher, Julia C.; Costa, Vivian Vasconcelos; Rust, Lauren N.; Bassit, Leda C.; Patel, Dharmeshkumar; Rezaei, Sahar; Moua, Justin; Santos, Felipe Rocha da Silva; Goncalves, Matheus Rodrigues; Queroz-Junior, Celso Martins; Marim, Fernanda Martins; Zhou, Longhu; Lee, Sujin; McBrayer, Tamara; De, Ramyani; Azadi, Niloufar; Salman, Mohammad; Zandi, Keivan; Amblard, Franck; Burwitz, Benjamin; Teixeira, Mauro M.; Schinazi, Raymond F. |
| Contributors: |
Martinez, Miguel Angel; National Institutes of Health; National Institute of Science and Technology in Dengue and Host-Microorganism Interaction; Fundacao de Amparo a Pesquisa do Estado de Minas Gerais |
| Source: |
Antimicrobial Agents and Chemotherapy ; volume 69, issue 5 ; ISSN 0066-4804 1098-6596 |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2025 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1128/aac.01889-24 |
| Availability: |
https://doi.org/10.1128/aac.01889-24; https://journals.asm.org/doi/pdf/10.1128/aac.01889-24 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; https://journals.asm.org/non-commercial-tdm-license |
| Accession Number: |
edsbas.FBBE0C69 |
| Database: |
BASE |