Therapeutic options against SARS-CoV-2 are underutilized. Two oral drugs, molnupiravir and paxlovid (nirmatrelvir/ritonavir), have received emergency use authorization. Initial trials suggested greater efficacy of paxlovid, but recent studies indicated comparable potency in older adults. Here, we compare both drugs in two animal models; the Roborovski dwarf hamster model for severe COVID-19-like lung infection and the ferret SARS-CoV-2 transmission model. Dwarf hamsters treated with either drug survive VOC omicron infection with equivalent lung titer reduction. Viral RNA copies in the upper respiratory tract of female ferrets receiving 1.25 mg/kg molnupiravir twice-daily are not significantly reduced, but infectious titers are lowered by >2 log orders and direct-contact transmission is stopped. Female ferrets dosed with 20 or 100 mg/kg nirmatrelvir/ritonavir twice-daily show 1–2 log order reduction of viral RNA copies and infectious titers, which correlates with low nirmatrelvir exposure in nasal turbinates. Virus replication resurges towards nirmatrelvir/ritonavir treatment end and virus transmits efficiently (20 mg/kg group) or partially (100 mg/kg group). Prophylactic treatment with 20 mg/kg nirmatrelvir/ritonavir does not prevent spread from infected ferrets, but prophylactic 5 mg/kg molnupiravir or 100 mg/kg nirmatrelvir/ritonavir block productive transmission. These data confirm reports of similar efficacy in older adults and inform on possible epidemiologic benefit of antiviral treatment.

针对 SARS-CoV-2 的治疗方案尚未得到充分利用。两种口服药物莫努匹拉韦和帕克洛维德（尼马瑞韦/利托那韦）已获得紧急使用授权。最初的试验表明帕克洛维的疗效更好，但最近的研究表明对老年人的疗效相当。在这里，我们比较了两种药物在两种动物模型中的作用；用于严重 COVID-19 样肺部感染的 Roborovski 侏儒仓鼠模型和雪貂 SARS-CoV-2 传播模型。用这两种药物治疗的侏儒仓鼠在 VOC omicron 感染中存活下来，肺效价也相应降低。每日两次接受 1.25 mg/kg molnupiravir 治疗的雌性雪貂上呼吸道中的病毒 RNA 拷贝数并未显着降低，但感染滴度降低了 >2 个对数级，并且直接接触传播停止。雌性雪貂每日两次服用 20 或 100 mg/kg 尼马瑞韦/利托那韦，病毒 RNA 拷贝数和感染滴度呈对数级减少 1-2 个数量级，这与鼻甲骨中尼马瑞韦暴露量较低相关。病毒复制在尼马曲韦/利托那韦治疗结束时重新出现，病毒有效传播（20 mg/kg 组）或部分传播（100 mg/kg 组）。使用 20 mg/kg 尼马瑞韦/利托那韦进行预防性治疗并不能阻止受感染雪貂的传播，但预防性使用 5 mg/kg 莫努匹拉韦或 100 mg/kg 尼马瑞韦/利托那韦可阻止生产性传播。这些数据证实了老年人中类似疗效的报告，并揭示了抗病毒治疗可能的流行病学益处。