Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840;
Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6771-6776. doi: 10.1073/pnas.1922083117. Epub 2020 Feb 13.
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.
中东呼吸综合征（MERS）病例不断出现，且病死率较高，这凸显了需要有有效的抗病毒治疗药物。瑞德西韦（GS-5734）可有效抑制中东呼吸综合征冠状病毒（MERS-CoV）在体外的复制，且在小鼠模型中对严重急性呼吸综合征冠状病毒（SARS-CoV）有效。在此，我们在恒河猴的中东呼吸综合征冠状病毒感染非人类灵长类动物模型中测试了预防性和治疗性瑞德西韦治疗的疗效。预防性瑞德西韦治疗在接种前 24 小时开始可完全预防 MERS-CoV 引起的临床疾病，强烈抑制呼吸道组织中的 MERS-CoV 复制，并防止肺部病变的形成。在接种后 12 小时开始的治疗性瑞德西韦治疗也提供了明显的临床益处，临床症状减少，肺部病毒复制减少，肺部病变的出现和严重程度降低。本研究结果支持在 MERS 临床试验中测试瑞德西韦治疗的疗效，并可能也适用于包括目前新出现的新型冠状病毒 2019-nCoV 在内的更广泛的冠状病毒。
