Ebola viral dynamics in nonhuman primates provides insights into virus immuno-pathogenesis and antiviral strategies

Nat Commun. 2018 Oct 1;9(1):4013. doi: 10.1038/s41467-018-06215-z.

Abstract

Despite several clinical trials implemented, no antiviral drug could demonstrate efficacy against Ebola virus. In non-human primates, early initiation of polymerase inhibitors favipiravir and remdesivir improves survival, but whether they could be effective in patients is unknown. Here we analyze the impact of antiviral therapy by using a mathematical model that integrates virological and immunological data of 44 cynomolgus macaques, left untreated or treated with favipiravir. We estimate that favipiravir has a ~50% efficacy in blocking viral production, which results in reducing virus growth and cytokine storm while IFNα reduces cell susceptibility to infection. Simulating the effect of delayed initiations of treatment, our model predicts survival rates of 60% for favipiravir and 100% for remdesivir when treatment is initiated within 3 and 4 days post infection, respectively. These results improve the understanding of Ebola immuno-pathogenesis and can help optimize antiviral evaluation in future outbreaks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Amides / therapeutic use
  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Ebolavirus / drug effects
  • Ebolavirus / immunology*
  • Ebolavirus / pathogenicity*
  • Female
  • Hemorrhagic Fever, Ebola / drug therapy*
  • Hemorrhagic Fever, Ebola / immunology*
  • Hemorrhagic Fever, Ebola / virology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology*
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use
  • Macaca
  • Models, Theoretical
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use
  • Survival Analysis
  • Time Factors
  • Viral Load / drug effects
  • Viral Load / immunology

Substances

  • Amides
  • Antiviral Agents
  • Cytokines
  • Interferon-alpha
  • Pyrazines
  • favipiravir