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Combating yellow fever virus with 7-deaza-7-fluoro-2'-C-methyladenosine
Julia C LeCher1, Vivian Vasconcelos Costa2, Lauren N Rust3
1Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Antimicrobial Agents and Chemotherapy
|April 14, 2025
Summary
A novel compound, 7-deaza-7-fluoro-2'-C-methyladenosine (DFA), shows strong potential as an antiviral treatment for Yellow fever virus (YFV). This drug effectively reduces YFV replication and liver damage in preclinical models.
Area of Science:
- Virology
- Infectious Diseases
- Drug Discovery
Background:
- Yellow fever virus (YFV) is a severe zoonotic flavivirus with no approved antiviral treatments.
- YFV is transmitted by mosquitoes in tropical regions of Africa and South America.
- Previous research identified 7-deaza-7-fluoro-2 -C-methyladenosine (DFA) as a potential YFV inhibitor.
Purpose of the Study:
- To evaluate the anti-flavivirus activity of DFA, specifically against YFV.
- To assess DFA's efficacy and safety profile both in vitro and in vivo.
Main Methods:
- In vitro assays were performed using YFV vaccine strain (YFV-17D) and a clinical isolate (DakH1279).
- In vivo efficacy was tested in A129 and AG129 mouse models infected with YFV.
- Key indicators of liver damage, including alanine transaminase levels and indocyanine green clearance, were measured.
Main Results:
- DFA demonstrated potent sub-micromolar activity against YFV in vitro with low cytotoxicity.
- DFA significantly reduced viral replication in the livers of infected mice.
- Treatment with DFA ameliorated YFV-induced liver damage markers in vivo.
Conclusions:
- DFA is a potent inhibitor of Yellow fever virus.
- DFA shows promise as a therapeutic agent for YFV infections.
- Further development of DFA as a pan-flavivirus therapeutic is warranted.
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