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

Vincent Madelain (), Sylvain Baize, Frédéric Jacquot, Stéphanie Reynard, Alexandra Fizet, Stephane Barron, Caroline Solas, Bruno Lacarelle, Caroline Carbonnelle, France Mentré, Hervé Raoul, Xavier Lamballerie and Jérémie Guedj
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Vincent Madelain: Université Paris Diderot, Sorbonne Paris Cité Paris
Sylvain Baize: Centre International de Recherche en Infectiologie
Frédéric Jacquot: US003 Inserm
Stéphanie Reynard: Centre International de Recherche en Infectiologie
Alexandra Fizet: Centre International de Recherche en Infectiologie
Stephane Barron: US003 Inserm
Caroline Solas: Laboratoire de Pharmacocinétique et Toxicologie
Bruno Lacarelle: Laboratoire de Pharmacocinétique et Toxicologie
Caroline Carbonnelle: US003 Inserm
France Mentré: Université Paris Diderot, Sorbonne Paris Cité Paris
Hervé Raoul: US003 Inserm
Xavier Lamballerie: UMR “Emergence des Pathologies Virales” (EPV: Aix-Marseille university - IRD 190 - Inserm 1207 - EHESP) - Institut Hospitalo-Universitaire Méditerranée Infection
Jérémie Guedj: Université Paris Diderot, Sorbonne Paris Cité Paris

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06215-z

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