Favipiravir is a broad-spectrum antiviral agent that has demonstrated efficacy against Ebola virus (EBOV) in rodents. However, there are no published reports of favipiravir efficacy for filovirus infection of nonhuman primates (NHPs). Here we evaluated the pharmacokinetic profile of favipiravir in NHPs, as well as in vivo efficacy against two filoviruses, EBOV and Marburg virus (MARV). While no survival benefit was observed in two studies employing once- or twice-daily oral dosing of favipiravir during EBOV infection of NHPs, an antiviral effect was observed in terms of extended time-to-death and reduced levels of viral RNA. However, oral dosing in biosafety level-4 (BSL-4) presents logistical and technical challenges, and repeated anesthesia events may potentially worsen survival outcome in animals. For the third study of treatment of MARV infection, we therefore made use of catheters, jackets, and tethers for intravenous (IV) dosing and blood collection, which minimized the requirement for repeated anesthesia events. When MARV infection was treated with IV favipiravir, five of six animals (83%) survived infection, while all untreated NHPs succumbed. An accompanying report presents the results of favipiravir treatment of EBOV infection in mice.

Favipiravir是一种广谱抗病毒药物，已证明对啮齿动物具有抗埃博拉病毒（EBOV）的功效。但是，尚无公开的文献报道favipiravir对非人类灵长类动物（NHPs）的细丝病毒感染有疗效。在这里，我们评估了法维拉韦在NHPs以及体内的药代动力学特征对两种丝状病毒EBOV和Marburg病毒（MARV）的功效。尽管两项研究在NHP的EBOV感染期间使用favipiravir每日一次或两次口服口服给药的两项研究均未观察到生存益处，但从延长死亡时间和降低病毒RNA水平方面观察到了抗病毒作用。然而，生物安全级别4（BSL-4）的口服剂量提出了后勤和技术难题，重复麻醉事件可能会恶化动物的生存结果。因此，对于第三项MARV感染的治疗，我们使用导管，护套和系绳进行静脉内（IV）给药和采血，从而最大程度地减少了重复麻醉事件的需要。当用IV法维吡韦治疗MARV感染时，六只动物中有五只（83％）幸免于感染，而所有未治疗的NHP均服从。