Morrey John D, Taro Brandon S, Siddharthan Venkatraman, Wang Hong, Smee Donald F, Christensen Andrew J, Furuta Yousuke
Institute for Antiviral Research, Utah State University, 4700 Old Main Hill, UT 84322-4700, USA.
Antiviral Res. 2008 Dec;80(3):377-9. doi: 10.1016/j.antiviral.2008.07.009. Epub 2008 Aug 30.
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.
我们在此描述,一种吡嗪衍生物T-705(6-氟-3-羟基-2-吡嗪甲酰胺)对啮齿动物的西尼罗河病毒致死性感染具有保护作用。在皮下接种病毒攻击后4小时开始,每天两次给予200mg/kg的口服T-705,可保护小鼠和仓鼠免受西尼罗河病毒诱导的死亡,并降低脑中病毒蛋白表达和病毒RNA水平。当在小鼠皮下接种病毒攻击后1天开始每天两次给药时,最小有效口服剂量在20至65mg/kg之间。治疗可延迟至病毒攻击后2天,仍能在小鼠中达到疗效。应考虑进一步开发该化合物用于治疗西尼罗河病毒。