The coronavirus disease 2019 (COVID-19) pandemic is having a catastrophic impact on human health¹. Widespread community transmission has triggered stringent distancing measures with severe socio-economic consequences. Gaining control of the pandemic will depend on the interruption of transmission chains until vaccine-induced or naturally acquired protective herd immunity arises. However, approved antiviral treatments such as remdesivir and reconvalescent serum cannot be delivered orally^2,3, making them poorly suitable for transmission control. We previously reported the development of an orally efficacious ribonucleoside analogue inhibitor of influenza viruses, MK-4482/EIDD-2801 (refs. ^4,5), that was repurposed for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently in phase II/III clinical trials (NCT04405570 and NCT04405739). Here, we explored the efficacy of therapeutically administered MK-4482/EIDD-2801 to mitigate SARS-CoV-2 infection and block transmission in the ferret model, given that ferrets and related members of the weasel genus transmit the virus efficiently with minimal clinical signs^6,7,8,9, which resembles the spread in the human young-adult population. We demonstrate high SARS-CoV-2 burden in nasal tissues and secretions, which coincided with efficient transmission through direct contact. Therapeutic treatment of infected animals with MK-4482/EIDD-2801 twice a day significantly reduced the SARS-CoV-2 load in the upper respiratory tract and completely suppressed spread to untreated contact animals. This study identified oral MK-4482/EIDD-2801 as a promising antiviral countermeasure to break SARS-CoV-2 community transmission chains.

2019 年冠状病毒病 (COVID-19) 大流行正在对人类健康造成灾难性影响¹。广泛的社区传播引发了严格的隔离措施，造成了严重的社会经济后果。控制大流行将取决于传播链的​​中断，直到疫苗诱导或自然获得的保护性群体免疫出现。然而，经批准的抗病毒治疗（例如瑞德西韦和恢复期血清）不能口服给药^2,3，这使得它们不太适合传播控制。^{我们之前报道了一种口服有效的流感病毒核糖核苷类似物抑制剂 MK-4482/EIDD-2801（参考文献4,5} ）的开发，该抑制剂被重新用于对抗严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)目前正在进行II/III期临床试验（NCT04405570和NCT04405739）。在这里，我们探讨了治疗性施用 MK-4482/EIDD-2801 在雪貂模型中减轻 SARS-CoV-2 感染和阻止传播的功效，因为雪貂和黄鼠狼属的相关成员可以在最小的临床症状下有效传播病毒^6,7,8,9，类似于人类年轻人口中的传播。我们证明鼻组织和分泌物中存在较高的 SARS-CoV-2 负担，这与通过直接接触的有效传播相一致。每天两次用 MK-4482/EIDD-2801 对受感染的动物进行治疗，显着降低了上呼吸道中的 SARS-CoV-2 负荷，并完全抑制了向未经治疗的接触动物的传播。这项研究确定口服 MK-4482/EIDD-2801 是一种有前途的抗病毒对策，可以打破 SARS-CoV-2 社区传播链。