Efficacy of Orally Administered T-705 Pyrazine Analog on Lethal West Nile Virus Infection in Rodents

Antiviral Res. 2008 Dec;80(3):377-9. doi: 10.1016/j.antiviral.2008.07.009. Epub 2008 Aug 30.

Abstract

We describe herein that a pyrazine derivative, T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide), is protective for a lethal West Nile virus infection in rodents. Oral T-705 at 200 mg/kg administered twice daily beginning 4h after subcutaneous (s.c.) viral challenge protected mice and hamsters against WNV-induced mortality, and reduced viral protein expression and viral RNA in brains. The minimal effective oral dose was between 20 and 65 mg/kg when administered twice a day beginning 1 day after viral s.c. challenge of mice. Treatment could be delayed out to 2 days after viral challenge to still achieve efficacy in mice. Further development of this compound should be considered for treatment of WNV.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Amides / administration & dosage*
  • Animals
  • Brain / metabolism
  • Brain / virology
  • Cricetinae
  • Disease Models, Animal
  • Drug Administration Schedule
  • Female
  • Humans
  • Mesocricetus
  • Mice
  • Mice, Inbred C57BL
  • Pyrazines / administration & dosage*
  • West Nile Fever / drug therapy*
  • West Nile Fever / metabolism
  • West Nile Fever / virology
  • West Nile virus / drug effects*

Substances

  • Amides
  • Pyrazines
  • favipiravir