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

Antiviral Res. 2014 May;105:17-21. doi: 10.1016/j.antiviral.2014.02.014. Epub 2014 Feb 26.

Abstract

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 4log units with an IC90 of 110μM. 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.

Keywords: Antiviral testing; Ebolavirus; Mouse model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / therapeutic use*
  • Animals
  • Antiviral Agents / therapeutic use*
  • Disease Models, Animal
  • Ebolavirus / drug effects
  • Ebolavirus / isolation & purification*
  • Ebolavirus / physiology
  • Hemorrhagic Fever, Ebola / drug therapy*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pyrazines / therapeutic use*
  • Survival Analysis
  • Viral Load
  • Virus Replication / drug effects

Substances

  • Amides
  • Antiviral Agents
  • Pyrazines
  • favipiravir