Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection

被引:606
作者
de Wit, Emmie [1 ]
Feldmann, Friederike [2 ]
Cronin, Jacqueline [1 ]
Jordan, Robert [3 ]
Okumura, Atsushi [4 ]
Thomas, Tina [1 ]
Scott, Dana [2 ]
Cihlar, Tomas [3 ]
Feldmann, Heinz [1 ]
机构
[1] NIAID, Lab Virol, NIH, Hamilton, MT 59840 USA
[2] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT 59840 USA
[3] Gilead Sci, Biol Dept, Foster City, CA 94404 USA
[4] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY 10032 USA
关键词
MERS-CoV; antiviral; animal model; remdesivir; therapy; EBOLA-VIRUS; ORGANIZATION; THERAPIES; EFFICACY;
D O I
10.1073/pnas.1922083117
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.
引用
收藏
页码:6771 / 6776
页数:6
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