Remdesivir (GS-5734) Is Efficacious in Cynomolgus Macaques Infected With Marburg Virus

被引:43
|
作者
Porter, Danielle P. [1 ]
Weidner, Jessica M. [2 ,3 ]
Gomba, Laura [2 ,3 ]
Bannister, Roy [1 ]
Blair, Christiana [1 ]
Jordan, Robert [1 ]
Wells, Jay [2 ,3 ]
Wetzel, Kelly [2 ,3 ]
Garza, Nicole [2 ,3 ]
Van Tongeren, Sean [2 ,3 ]
Donnelly, Ginger [2 ,3 ]
Steffens, Jesse [2 ,3 ]
Moreau, Alicia [3 ]
Bearss, Jeremy [3 ]
Lee, Eric [3 ]
Bavari, Sina [3 ]
Cihlar, Tomas [1 ]
Warren, Travis K. [2 ,3 ]
机构
[1] Gilead Sci Inc, 333 Lakeside Dr, Foster City, CA 94404 USA
[2] Geneva Fdn, Tacoma, WA USA
[3] US Army Med Res Inst Infect Dis, Frederick, MD USA
来源
JOURNAL OF INFECTIOUS DISEASES | 2020年 / 222卷 / 11期
关键词
Marburg virus; filovirus; GS-5734; nonhuman primate; remdesivir; NONHUMAN-PRIMATES; EBOLA-VIRUS;
D O I
10.1093/infdis/jiaa290
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1894 / 1901
页数:8
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