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

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

Author information

1
IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité Paris, 75018, Paris, France. vincent.madelain@inserm.fr.
2
UBIVE, Institut Pasteur, Centre International de Recherche en Infectiologie, 69007, Lyon, France.
3
Laboratoire P4 Inserm-Jean Mérieux, US003 Inserm, 69365, Lyon, France.
4
Aix-Marseille Univ U105, APHM, SMARTc CRCM Inserm UMR1068 CNRS UMR7258, Hôpital La Timone, Laboratoire de Pharmacocinétique et Toxicologie, 13005, Marseille, France.
5
IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité Paris, 75018, Paris, France.
6
UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille university - IRD 190 - Inserm 1207 - EHESP) - Institut Hospitalo-Universitaire Méditerranée Infection, 13385, Marseille, France.

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.

PMID:
30275474
PMCID:
PMC6167368
DOI:
10.1038/s41467-018-06215-z
[Indexed for MEDLINE]
Free PMC Article

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