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Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model.

Abstract
Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg virus (variant Angola). Moreover, lower doses of T-705 and higher doses administered later during infection (day 3 or 4 post-infection) showed partial efficacy, with at least half the infected mice surviving. Accordingly, we observed reductions in infectious virus particles and virus RNA levels following drug treatment that appeared to correlate with survival. Our findings suggest that T-705 may be an effective therapeutic against Marburg virus and might be especially promising for use in the event of an outbreak, where it could be orally administered quickly and safely even after exposure.
AuthorsWenjun Zhu, Zirui Zhang, Shihua He, Gary Wong, Logan Banadyga, Xiangguo Qiu
JournalAntiviral research (Antiviral Res) Vol. 151 Pg. 39-49 (03 2018) ISSN: 1872-9096 [Electronic] Netherlands
PMID29369776 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCrown Copyright © 2018. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Amides
  • Antiviral Agents
  • Pyrazines
  • RNA, Viral
  • favipiravir
Topics
  • Administration, Oral
  • Amides (administration & dosage, pharmacology)
  • Animals
  • Antiviral Agents (administration & dosage, pharmacology)
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Female
  • Marburg Virus Disease (drug therapy)
  • Marburgvirus (drug effects)
  • Mice, Inbred BALB C
  • Pyrazines (administration & dosage, pharmacology)
  • RNA, Viral (metabolism)
  • Survival Analysis
  • Vero Cells
  • Viral Load (drug effects)
  • Virus Replication (drug effects)

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