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- Title
Ebola viral dynamics in nonhuman primates provides insights into virus immuno-pathogenesis and antiviral strategies.
- Authors
Madelain, Vincent; Baize, Sylvain; Jacquot, Frédéric; Reynard, Stéphanie; Fizet, Alexandra; Barron, Stephane; Solas, Caroline; Lacarelle, Bruno; Carbonnelle, Caroline; Mentré, France; Raoul, Hervé; de Lamballerie, Xavier; Guedj, Jérémie
- 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. Optimization of antiviral therapy can be crucial in the management of Ebola virus outbreaks. Here, Madelain et al. use an integrative mathematical model to correlate the dose and the time of treatment initiation with survival rate, enhanced immune response and viral clearance.
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-06215-z