The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset

Sci Rep. 2015 Oct 12;5:14775. doi: 10.1038/srep14775.

Abstract

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Amides / pharmacology*
  • Animals
  • Animals, Outbred Strains
  • Antibodies, Viral / biosynthesis*
  • Antibodies, Viral / blood
  • Antiviral Agents / pharmacology*
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Guinea Pigs
  • Humans
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin G / blood
  • Lassa Fever / drug therapy*
  • Lassa Fever / immunology
  • Lassa Fever / mortality
  • Lassa Fever / virology
  • Lassa virus / drug effects*
  • Lassa virus / pathogenicity
  • Lassa virus / physiology
  • Liver / drug effects
  • Liver / virology
  • Lung / drug effects
  • Lung / virology
  • Male
  • Pyrazines / pharmacology*
  • Ribavirin / pharmacology
  • Spleen / drug effects
  • Spleen / pathology
  • Spleen / virology
  • Survival Analysis
  • Viral Load / drug effects

Substances

  • Amides
  • Antibodies, Viral
  • Antiviral Agents
  • Immunoglobulin G
  • Pyrazines
  • Ribavirin
  • favipiravir