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Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever

We studied the therapeutic potential of favipiravir (T-705) for Lassa fever, both alone and in combination with ribavirin. Favipiravir suppressed Lassa virus replication in cell culture by 5 log(10) units. In a novel lethal mouse model, it lowered the viremia level and the virus load in organs and n...

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Autores principales: Oestereich, Lisa, Rieger, Toni, Lüdtke, Anja, Ruibal, Paula, Wurr, Stephanie, Pallasch, Elisa, Bockholt, Sabrina, Krasemann, Susanne, Muñoz-Fontela, César, Günther, Stephan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760419/
https://www.ncbi.nlm.nih.gov/pubmed/26531247
http://dx.doi.org/10.1093/infdis/jiv522
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author Oestereich, Lisa
Rieger, Toni
Lüdtke, Anja
Ruibal, Paula
Wurr, Stephanie
Pallasch, Elisa
Bockholt, Sabrina
Krasemann, Susanne
Muñoz-Fontela, César
Günther, Stephan
author_facet Oestereich, Lisa
Rieger, Toni
Lüdtke, Anja
Ruibal, Paula
Wurr, Stephanie
Pallasch, Elisa
Bockholt, Sabrina
Krasemann, Susanne
Muñoz-Fontela, César
Günther, Stephan
author_sort Oestereich, Lisa
collection PubMed
description We studied the therapeutic potential of favipiravir (T-705) for Lassa fever, both alone and in combination with ribavirin. Favipiravir suppressed Lassa virus replication in cell culture by 5 log(10) units. In a novel lethal mouse model, it lowered the viremia level and the virus load in organs and normalized levels of cell-damage markers. Treatment with 300 mg/kg per day, commenced 4 days after infection, when the viremia level had reached 4 log(10) virus particles/mL, rescued 100% of Lassa virus–infected mice. We found a synergistic interaction between favipiravir and ribavirin in vitro and an increased survival rate and extended survival time when combining suboptimal doses in vivo.
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spelling pubmed-47604192016-02-22 Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever Oestereich, Lisa Rieger, Toni Lüdtke, Anja Ruibal, Paula Wurr, Stephanie Pallasch, Elisa Bockholt, Sabrina Krasemann, Susanne Muñoz-Fontela, César Günther, Stephan J Infect Dis Major Articles and Brief Reports We studied the therapeutic potential of favipiravir (T-705) for Lassa fever, both alone and in combination with ribavirin. Favipiravir suppressed Lassa virus replication in cell culture by 5 log(10) units. In a novel lethal mouse model, it lowered the viremia level and the virus load in organs and normalized levels of cell-damage markers. Treatment with 300 mg/kg per day, commenced 4 days after infection, when the viremia level had reached 4 log(10) virus particles/mL, rescued 100% of Lassa virus–infected mice. We found a synergistic interaction between favipiravir and ribavirin in vitro and an increased survival rate and extended survival time when combining suboptimal doses in vivo. Oxford University Press 2016-03-15 2015-11-03 /pmc/articles/PMC4760419/ /pubmed/26531247 http://dx.doi.org/10.1093/infdis/jiv522 Text en © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact journals.permissions@oup.com.
spellingShingle Major Articles and Brief Reports
Oestereich, Lisa
Rieger, Toni
Lüdtke, Anja
Ruibal, Paula
Wurr, Stephanie
Pallasch, Elisa
Bockholt, Sabrina
Krasemann, Susanne
Muñoz-Fontela, César
Günther, Stephan
Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever
title Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever
title_full Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever
title_fullStr Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever
title_full_unstemmed Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever
title_short Efficacy of Favipiravir Alone and in Combination With Ribavirin in a Lethal, Immunocompetent Mouse Model of Lassa Fever
title_sort efficacy of favipiravir alone and in combination with ribavirin in a lethal, immunocompetent mouse model of lassa fever
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760419/
https://www.ncbi.nlm.nih.gov/pubmed/26531247
http://dx.doi.org/10.1093/infdis/jiv522
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