Efficacy of orally administered T-705 pyrazine analog on lethal West Nile virus infection in rodents

• Published in: Antiviral research 2008-12, Vol.80 (3), p.377-379
• Main Authors: Morrey, John D., Taro, Brandon S., Siddharthan, Venkatraman, Wang, Hong, Smee, Donald F., Christensen, Andrew J., Furuta, Yousuke
• Format: Article
• Language: English
• Subjects: 6-Fluoro-3-hydroxy-2-pyrazinecarboxamide; Administration, Oral; Amides - administration & dosage; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Brain - metabolism; Brain - virology; Cricetinae; Disease Models, Animal; Drug Administration Schedule; Female; Hamsters; Humans; Medical sciences; Mesocricetus; Mice; Mice, Inbred C57BL; Pharmacology. Drug treatments; Pyrazines - administration & dosage; T-705; West Nile Fever - drug therapy; West Nile Fever - metabolism; West Nile Fever - virology; West Nile virus; West Nile virus - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2008.07.009

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 4 h 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.