Gilead Sciences Inc., Foster City, California, USA.
Geneva Foundation, Tacoma, Washington, USA.
J Infect Dis. 2020 Nov 9;222(11):1894-1901. doi: 10.1093/infdis/jiaa290.
Marburg virus (MARV) is a filovirus with documented human case-fatality rates of up to 90%. Here, we evaluated the therapeutic efficacy of remdesivir (GS-5734) in nonhuman primates experimentally infected with MARV. Beginning 4 or 5 days post inoculation, cynomolgus macaques were treated once daily for 12 days with vehicle, 5 mg/kg remdesivir, or a 10-mg/kg loading dose followed by 5 mg/kg remdesivir. All vehicle-control animals died, whereas 83% of animals receiving a 10-mg/kg loading dose of remdesivir survived, as did 50% of animals receiving a 5-mg/kg remdesivir regimen. Remdesivir-treated animals exhibited improved clinical scores, lower plasma viral RNA, and improved markers of kidney function, liver function, and coagulopathy versus vehicle-control animals. The small molecule remdesivir showed therapeutic efficacy in this Marburg virus disease model with treatment initiation 5 days post inoculation, supporting further assessment of remdesivir for the treatment of Marburg virus disease in humans.
马尔堡病毒(MARV)是一种丝状病毒,有记录的人类病死率高达 90%。在这里,我们评估了瑞德西韦(GS-5734)在感染 MARV 的非人灵长类动物中的治疗效果。从接种后 4 或 5 天开始,恒河猴每天接受一次治疗,持续 12 天,分别接受载体、5mg/kg 瑞德西韦或 10mg/kg 负荷剂量加 5mg/kg 瑞德西韦。所有接受载体对照治疗的动物均死亡,而接受 10mg/kg 瑞德西韦负荷剂量治疗的动物中有 83%存活,接受 5mg/kg 瑞德西韦治疗方案的动物中有 50%存活。与载体对照动物相比,瑞德西韦治疗动物的临床评分改善,血浆病毒 RNA 降低,肾功能、肝功能和凝血功能障碍标志物改善。小分子瑞德西韦在这种马尔堡病毒病模型中显示出治疗效果,接种后 5 天开始治疗,支持进一步评估瑞德西韦治疗人类马尔堡病毒病的效果。