Early control of viral load by favipiravir promotes survival to Ebola virus challenge and prevents cytokine storm in non-human primates

PLoS Negl Trop Dis. 2021 Mar 29;15(3):e0009300. doi: 10.1371/journal.pntd.0009300. eCollection 2021 Mar.

Abstract

Ebola virus has been responsible for two major epidemics over the last several years and there has been a strong effort to find potential treatments that can improve the disease outcome. Antiviral favipiravir was thus tested on non-human primates infected with Ebola virus. Half of the treated animals survived the Ebola virus challenge, whereas the infection was fully lethal for the untreated ones. Moreover, the treated animals that did not survive died later than the controls. We evaluated the hematological, virological, biochemical, and immunological parameters of the animals and performed proteomic analysis at various timepoints of the disease. The viral load strongly correlated with dysregulation of the biological functions involved in pathogenesis, notably the inflammatory response, hemostatic functions, and response to stress. Thus, the management of viral replication in Ebola virus disease is of crucial importance in preventing the immunopathogenic disorders and septic-like shock syndrome generally observed in Ebola virus-infected patients.

MeSH terms

  • Amides / pharmacology*
  • Animals
  • Antiviral Agents / pharmacology*
  • Cytokine Release Syndrome / prevention & control*
  • Cytokines / blood
  • Disease Models, Animal
  • Ebolavirus / drug effects*
  • Hemorrhagic Fever, Ebola / drug therapy*
  • Hemorrhagic Fever, Ebola / pathology
  • Hemorrhagic Fever, Ebola / veterinary
  • Macaca fascicularis
  • Pyrazines / pharmacology*
  • T-Lymphocytes / immunology
  • Viral Load / drug effects*
  • Viremia / blood
  • Viremia / pathology
  • Virus Replication / drug effects

Substances

  • Amides
  • Antiviral Agents
  • Cytokines
  • Pyrazines
  • favipiravir

Grants and funding

The authors received no specific funding for this work.