title: Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model.
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.
authors.affiliation: Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany; German Centre for Infection Research (DZIF), Partner Site Hamburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Oestereich
authors.affiliation: Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Lüdtke
authors.affiliation: Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany; German Centre for Infection Research (DZIF), Partner Site Hamburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wurr
authors.affiliation: Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany; German Centre for Infection Research (DZIF), Partner Site Hamburg, Germany.
authors.forename: Toni
authors.initials: T
authors.lastname: Rieger
authors.affiliation: Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg, Germany.
authors.forename: César
authors.initials: C
authors.lastname: Muñoz-Fontela
authors.affiliation: Bernhard-Nocht-Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany; German Centre for Infection Research (DZIF), Partner Site Hamburg, Germany. Electronic address: guenther@bni.uni-hamburg.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Günther
mesh_terms: D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000187:drug effects / Q000302:isolation & purification* / Q000502:physiology; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011719:Pyrazines / Q000627:therapeutic use*; D016019:Survival Analysis; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000577:Amides; D000998:Antiviral Agents; D011719:Pyrazines; C462182:favipiravir
keywords: Antiviral testing; Ebolavirus; Mouse model