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Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2

机译：Rhehus Macaques remdesivir的临床益处感染SARS-COV-2

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The nucleotide analogue prodrug remdesivir reduces viral load and lung disease in a rhesus macaque model of SARS-CoV-2 infection.Effective therapies to treat coronavirus disease 2019 (COVID-19) are urgently needed. While many investigational, approved, and repurposed drugs have been suggested as potential treatments, preclinical data from animal models can guide the search for effective treatments by ruling out those that lack efficacy in vivo. Remdesivir (GS-5734) is a nucleotide analogue prodrug with broad antiviral activity(1,2)that is currently being investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration(3,4). In animal models, remdesivir was effective against infection with Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV)(2,5,6). In vitro, remdesivir inhibited replication of SARS-CoV-2(7,8). Here we investigate the efficacy of remdesivir in a rhesus macaque model of SARS-CoV-2 infection(9). Unlike vehicle-treated animals, macaques treated with remdesivir did not show signs of respiratory disease; they also showed reduced pulmonary infiltrates on radiographs and reduced virus titres in bronchoalveolar lavages twelve hours after the first dose. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, remdesivir-treated animals had lower lung viral loads and reduced lung damage. Thus, treatment with remdesivir initiated early during infection had a clinical benefit in rhesus macaques infected with SARS-CoV-2. Although the rhesus macaque model does not represent the severe disease observed in some patients with COVID-19, our data support the early initiation of remdesivir treatment in patients with COVID-19 to prevent progression to pneumonia.
机译：核苷酸类似物前药Remdesivir减少了SARS-COV-2感染的恒河猴模型中的病毒载荷和肺病。迫切需要治疗冠状病毒疾病的疗法（Covid-19）。虽然已经提出了许多调查，批准和重新培养的药物作为潜在的治疗，但动物模型的临床前数据可以通过裁定缺乏体内疗效的人来指导有效治疗。 RemdesiviR（GS-5734）是具有广泛抗病毒活性（1,2）的核苷酸类似物前药（1,2），目前正在Covid-19临床试验中研究，最近收到了美国食品和药物管理局的紧急使用授权（3,4）。在动物模型中，RemdesiviR对中东呼吸综合征冠状病毒（MERS-COV）和严重急性呼吸综合征冠状病毒（SARS-COV）的感染有效（2,5,6）。体外，Remdesivir抑制SARS-COV-2（7,8）的复制。在这里，我们研究Remdesivir在SARS-COV-2感染的恒星猕猴模型中的疗效（9）。与车辆治疗的动物不同，用雷德氏菌治疗的猕猴没有显示出呼吸系统疾病的迹象;它们还表现出X型X型X型肺渗透，并在一剂后12小时后的支气管肺泡灌洗液中减少病毒滴度。来自上呼吸道的病毒脱落未通过雷级肽治疗减少。在尸检时，雷德米血症治疗的动物具有较低的肺病毒载荷和降低的肺部损伤。因此，在感染期间早期开始的Remdesivir治疗在感染SARS-COV-2的恒河猴中具有临床益处。虽然恒河猴模型不代表在一些Covid-19患者中观察到的严重疾病，但我们的数据支持患有Covid-19患者的RemdesiviR治疗的早期开始，以防止进入肺炎。

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