Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2−infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 于 2019 年 12 月在武汉出现后迅速在全球传播。由于没有具体的治疗和预防方案，该病毒已感染数百万人，其中超过 50 万人被感染。死于病毒性疾病 COVID-19。对有效治疗的迫切需要以及小动物感染模型的缺乏导致了使用重新用途药物的临床试验，而没有其体内疗效的临床前证据。我们在叙利亚仓鼠中建立了感染模型，以评估小分子对感染和传播的功效。用低剂量的法匹拉韦或羟氯喹加（不加）阿奇霉素治疗感染 SARS-CoV-2 的仓鼠，分别导致病毒水平轻度降低或无降低。然而，高剂量的法匹拉韦显着降低了肺部感染性病毒滴度，并显着改善了肺部组织病理学。此外，高剂量的法匹拉韦减少了直接接触引起的病毒传播，而羟氯喹则无法起到预防作用。羟氯喹的药代动力学模型表明，整个肺部暴露于该药物并不会导致失败。因此，我们关于羟氯喹的数据（以及之前在猕猴和雪貂身上的报告）并没有为在 COVID-19 患者中使用该药物提供科学依据。相比之下，法匹拉韦的结果表明，无毒剂量的抗病毒药物在小动物模型中对 SARS-CoV-2 表现出显着的保护作用。需要进行临床研究来评估是否可以在人体中实现类似的抗病毒作用而不产生毒性作用。