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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Vincent Madelain, Sylvain Baize, Frédéric Jacquot, Stéphanie Reynard, Alexandra Fizet, Stephane Barron, Caroline Solas, Bruno Lacarelle, Caroline Carbonnelle, France Mentré, Hervé Raoul, Xavier de Lamballerie, Jérémie Guedj

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. More... »

PAGES

4013

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-06215-z

DOI

http://dx.doi.org/10.1038/s41467-018-06215-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107245420

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30275474


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