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The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Si...

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Autores principales: Safronetz, David, Rosenke, Kyle, Westover, Jonna B., Martellaro, Cynthia, Okumura, Atsushi, Furuta, Yousuke, Geisbert, Joan, Saturday, Greg, Komeno, Takashi, Geisbert, Thomas W., Feldmann, Heinz, Gowen, Brian B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600983/
https://www.ncbi.nlm.nih.gov/pubmed/26456301
http://dx.doi.org/10.1038/srep14775
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author Safronetz, David
Rosenke, Kyle
Westover, Jonna B.
Martellaro, Cynthia
Okumura, Atsushi
Furuta, Yousuke
Geisbert, Joan
Saturday, Greg
Komeno, Takashi
Geisbert, Thomas W.
Feldmann, Heinz
Gowen, Brian B.
author_facet Safronetz, David
Rosenke, Kyle
Westover, Jonna B.
Martellaro, Cynthia
Okumura, Atsushi
Furuta, Yousuke
Geisbert, Joan
Saturday, Greg
Komeno, Takashi
Geisbert, Thomas W.
Feldmann, Heinz
Gowen, Brian B.
author_sort Safronetz, David
collection PubMed
description With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.
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spelling pubmed-46009832015-10-21 The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset Safronetz, David Rosenke, Kyle Westover, Jonna B. Martellaro, Cynthia Okumura, Atsushi Furuta, Yousuke Geisbert, Joan Saturday, Greg Komeno, Takashi Geisbert, Thomas W. Feldmann, Heinz Gowen, Brian B. Sci Rep Article With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs. Nature Publishing Group 2015-10-12 /pmc/articles/PMC4600983/ /pubmed/26456301 http://dx.doi.org/10.1038/srep14775 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Safronetz, David
Rosenke, Kyle
Westover, Jonna B.
Martellaro, Cynthia
Okumura, Atsushi
Furuta, Yousuke
Geisbert, Joan
Saturday, Greg
Komeno, Takashi
Geisbert, Thomas W.
Feldmann, Heinz
Gowen, Brian B.
The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset
title The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset
title_full The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset
title_fullStr The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset
title_full_unstemmed The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset
title_short The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset
title_sort broad-spectrum antiviral favipiravir protects guinea pigs from lethal lassa virus infection post-disease onset
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600983/
https://www.ncbi.nlm.nih.gov/pubmed/26456301
http://dx.doi.org/10.1038/srep14775
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