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Activity of T-1106 in a hamster model of yellow Fever virus infection.

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.
AuthorsJustin G Julander, Yousuke Furuta, Kristiina Shafer, Robert W Sidwell
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 51 Issue 6 Pg. 1962-6 (Jun 2007) ISSN: 0066-4804 [Print] United States
PMID17420215 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Amides
  • Antiviral Agents
  • Pyrazines
  • favipiravir
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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