Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model

被引:347
作者
Oestereich, Lisa [1 ,2 ]
Luedtke, Anja [1 ,3 ]
Wurr, Stephanie [1 ,2 ]
Rieger, Toni [1 ,2 ]
Munoz-Fontela, Cesar [1 ,3 ]
Guenther, Stephan [1 ,2 ]
机构
[1] Bernhard Nocht Inst Trop Med, Dept Virol, D-20359 Hamburg, Germany
[2] German Ctr Infect Res DZIF, Hamburg, Germany
[3] Leibniz Inst Expt Virol, Heinrich Pette Inst, D-20251 Hamburg, Germany
关键词
Ebolavirus; Mouse model; Antiviral testing; IN-VIVO ACTIVITIES; NONHUMAN-PRIMATES; EFFICACY; THERAPY; VITRO; PROTECTION;
D O I
10.1016/j.antiviral.2014.02.014
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Outbreaks of Ebola hemorrhagic fever in sub-Saharan Africa are associated with case fatality rates of up to 90%. Currently, neither a vaccine nor an effective antiviral treatment is available for use in humans. Here, we evaluated the efficacy of the pyrazinecarboxamide derivative T-705 (favipiravir) against Zaire Ebola virus (EBOV) in vitro and in vivo. T-705 suppressed replication of Zaire EBOV in cell culture by 4 log units with an IC90 of 110 mu M. Mice lacking the type I interferon receptor (IFNAR(-/-)) were used as in vivo model for Zaire EBOV-induced disease. Initiation of T-705 administration at day 6 post infection induced rapid virus clearance, reduced biochemical parameters of disease severity, and prevented a lethal outcome in 100% of the animals. The findings suggest that T-705 is a candidate for treatment of Ebola hemorrhagic fever. (c) 2014 The Authors. Published by Elsevier B.V.
引用
收藏
页码:17 / 21
页数:5
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