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Intracellular conversion and in vivo dose response of favipiravir (T-705) in rodents infected with Ebola virus
Antiviral Research ( IF 4.5 ) Pub Date : 2017-12-28 , DOI: 10.1016/j.antiviral.2017.12.020
Sandra L. Bixler , Thomas M. Bocan , Jay Wells , Kelly S. Wetzel , Sean A. Van Tongeren , Nicole L. Garza , Ginger Donnelly , Lisa H. Cazares , Veronica Soloveva , Lisa Welch , Carol Epstein , Li-Fang Liang , Dennis Giesing , Robert Lenk , Sina Bavari , Travis K. Warren

During the 2013–2016 Ebola virus (EBOV) outbreak in West Africa, our team at USAMRIID evaluated the antiviral activity of a number of compounds, including favipiravir (T-705), in vitro and in mouse and nonhuman primate (NHP) models of Ebola virus disease. In this short communication, we present our findings for favipiravir in cell culture and in mice, while an accompanying paper presents the results of NHP studies. We confirmed previous reports that favipiravir has anti-EBOV activity in mice. Additionally, we found that the active form of favipiravir is generated in mice in tissues relevant for the pathogenesis of EBOV infection. Finally, we observed that protection can be achieved in mice down to 8 mg/kg/day, which is lower than the dosing regimens previously reported. An accompanying paper reports the results of treating nonhuman primates infected with EBOV or with Marburg virus with oral or intravenous favipiravir.



中文翻译:

法维拉韦(T-705)在感染埃博拉病毒的啮齿动物中的细胞内转化和体内剂量反应

在西非2013-2016埃博拉病毒(EBOV)爆发,我们的团队在USAMRIID评估了许多化合物的抗病毒活性,包括法匹拉韦(T-705),在体外以及埃博拉病毒病的小鼠和非人类灵长类动物(NHP)模型。在这段简短的交流中,我们介绍了在细胞培养和小鼠中使用favipiravir的发现,同时随附的论文介绍了NHP研究的结果。我们证实了先前的报道,表明favipiravir在小鼠中具有抗EBOV活性。此外,我们发现,favipiravir的活性形式是在小鼠中与EBOV感染的发病机理相关的组织中产生的。最后,我们观察到低至8 mg / kg / day的小鼠可以实现保护,这低于先前报道的给药方案。随附的论文报告了口服或静脉注射法维吡韦治疗感染EBOV或马堡病毒的非人类灵长类动物的结果。

更新日期:2017-12-28
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