Abstract |
Yellow fever virus (YFV) causes 30,000 deaths worldwide, despite the availability of a vaccine. There are no approved antiviral therapies for the treatment of YFV disease in humans, and, therefore, these studies were designed to investigate the anti-YFV properties of T-1106, a substituted pyrazine, in a hamster model of YFV disease. Intraperitoneal (i.p.) treatment with 100 mg/kg of body weight/day of T-1106 starting 4 h prior to virus inoculation and continuing twice daily through 7 days post-virus inoculation (dpi) resulted in significantly improved survival, alanine aminotransferase levels in the serum, weight gain, and mean day to death. Virus titer in the liver at 4 dpi was significantly reduced in treated animals, as determined by both quantitative real-time PCR and infectious cell culture assay. No toxicity ( weight loss or mortality) was observed at a dose of 100 mg/kg/day in sham-infected control animals. The observed minimal effective dose of T-1106 was 32 mg/kg/day administered either by oral or i.p. treatment. Therapeutic treatment was effective in significantly improving survival when T-1106 was administered beginning as late as 4 days after virus challenge with twice-daily treatment for 8 days at a dose of 100 mg/kg/day. With favorable safety, bioavailability, and postviral challenge treatment efficacy, T-1106 was effective in the treatment of disease in hamsters infected with YFV and should be further studied for potential use as a therapy for human YFV disease.
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Authors | Justin G Julander, Yousuke Furuta, Kristiina Shafer, Robert W Sidwell |
Journal | Antimicrobial agents and chemotherapy
(Antimicrob Agents Chemother)
Vol. 51
Issue 6
Pg. 1962-6
(Jun 2007)
ISSN: 0066-4804 [Print] United States |
PMID | 17420215
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amides
- Antiviral Agents
- Pyrazines
- favipiravir
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Topics |
- Amides
(administration & dosage, chemistry, pharmacology, therapeutic use)
- Animals
- Antiviral Agents
(chemistry, pharmacology, therapeutic use)
- Chlorocebus aethiops
- Cricetinae
- Disease Models, Animal
- Female
- Humans
- Mesocricetus
- Pyrazines
(administration & dosage, chemistry, pharmacology, therapeutic use)
- Treatment Outcome
- Vero Cells
- Yellow Fever
(drug therapy, mortality, virology)
- Yellow fever virus
(drug effects, pathogenicity, physiology)
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