Efficacy of orally administered T-705 pyrazine analog on lethal West Nile virus infection in rodents.
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.
Morrey
John D
JD
Institute for Antiviral Research, Utah State University, 4700 Old Main Hill, UT 84322-4700, USA. john.morrey@usu.edu
Taro
Brandon S
BS
Siddharthan
Venkatraman
V
Wang
Hong
H
Smee
Donald F
DF
Christensen
Andrew J
AJ
Furuta
Yousuke
Y