Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC₅₀ = 0.01 μM). Weaker activity is observed in Vero E6 cells (EC₅₀ = 1.65 μM) because of their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase of SARS-CoV-2. In mice infected with the chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared with vehicle-treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.

严重急性呼吸系统综合症冠状病毒2（SARS-CoV-2）是新型病毒性疾病COVID-19的病原体。由于没有批准的疗法，这种大流行说明了迫切需要针对SARS-CoV-2和未来出现的CoV的广谱抗病毒对策。我们报告说，雷姆昔韦（RDV）可以有效抑制SARS-CoV-2在人肺细胞和原代人气道上皮培养物中的复制（EC ₅₀  = 0.01μM）。在Vero E6细胞（EC ₅₀  = 1.65μM）中观察到较弱的活性，因为它们的RDV代谢能力较低。快速评估体内功效，我们设计了一种嵌合的SARS-CoV，该病毒编码RDV的病毒靶标，即SARS-CoV-2的RNA依赖性RNA聚合酶。与载体治疗的动物相比，在嵌合病毒感染的小鼠中，RDV的治疗性给药可减少肺部病毒载量并改善肺功能。这些数据表明，RDV在体外和体内均具有针对SARS-CoV-2的有效活性，从而支持其进一步的临床试验以治疗COVID-19。