Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever
Several viruses in the Arenaviridae family cause severe life-threatening hemorrhagic fever syndromes, which are considered neglected tropical diseases in endemic areas of Africa and South America. Ribavirin, the only licensed antiviral indicated for use has limited efficacy when treating advanced ca...
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| Format: | Online |
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Public Library of Science
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191123/ |
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pubmed-31911232011-10-21 Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever Mendenhall, Michelle Russell, Andrew Smee, Donald F. Hall, Jeffery O. Skirpstunas, Ramona Furuta, Yousuke Gowen, Brian B. Research Article Several viruses in the Arenaviridae family cause severe life-threatening hemorrhagic fever syndromes, which are considered neglected tropical diseases in endemic areas of Africa and South America. Ribavirin, the only licensed antiviral indicated for use has limited efficacy when treating advanced cases of disease and is associated with toxicity. In the present study, we use a model of acute arenaviral disease in guinea pigs based on infection with an adapted strain of the Pichindé arenavirus (PICV) to further preclinical development of a promising broad-spectrum antiviral drug candidate, favipiravir. Oral favipiravir was highly effective in the treatment of sick animals with marked fevers, as all recovered fully from lethal PICV infection even when therapy was initiated one week after virus challenge. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in serum virus loads and serum aspartate aminotransferase, an enzyme released into the bloodstream following tissue damage and a marker for severe arenaviral infections. Moreover, a sharp decrease in fever was observed shortly after the onset of treatment. Our findings support further development of favipiravir for the treatment of severe arenaviral infections, for which there are presently no safe and effective therapies for treating advanced cases of disease. Public Library of Science 2011-10-11 /pmc/articles/PMC3191123/ /pubmed/22022624 http://dx.doi.org/10.1371/journal.pntd.0001342 Text en Mendenhall et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Mendenhall, Michelle Russell, Andrew Smee, Donald F. Hall, Jeffery O. Skirpstunas, Ramona Furuta, Yousuke Gowen, Brian B. |
| spellingShingle |
Mendenhall, Michelle Russell, Andrew Smee, Donald F. Hall, Jeffery O. Skirpstunas, Ramona Furuta, Yousuke Gowen, Brian B. Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever |
| author_facet |
Mendenhall, Michelle Russell, Andrew Smee, Donald F. Hall, Jeffery O. Skirpstunas, Ramona Furuta, Yousuke Gowen, Brian B. |
| author_sort |
Mendenhall, Michelle |
| title |
Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever |
| title_short |
Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever |
| title_full |
Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever |
| title_fullStr |
Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever |
| title_full_unstemmed |
Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever |
| title_sort |
effective oral favipiravir (t-705) therapy initiated after the onset of clinical disease in a model of arenavirus hemorrhagic fever |
| description |
Several viruses in the Arenaviridae family cause severe life-threatening hemorrhagic fever syndromes, which are considered neglected tropical diseases in endemic areas of Africa and South America. Ribavirin, the only licensed antiviral indicated for use has limited efficacy when treating advanced cases of disease and is associated with toxicity. In the present study, we use a model of acute arenaviral disease in guinea pigs based on infection with an adapted strain of the Pichindé arenavirus (PICV) to further preclinical development of a promising broad-spectrum antiviral drug candidate, favipiravir. Oral favipiravir was highly effective in the treatment of sick animals with marked fevers, as all recovered fully from lethal PICV infection even when therapy was initiated one week after virus challenge. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in serum virus loads and serum aspartate aminotransferase, an enzyme released into the bloodstream following tissue damage and a marker for severe arenaviral infections. Moreover, a sharp decrease in fever was observed shortly after the onset of treatment. Our findings support further development of favipiravir for the treatment of severe arenaviral infections, for which there are presently no safe and effective therapies for treating advanced cases of disease. |
| publisher |
Public Library of Science |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191123/ |
| _version_ |
1611480067571974144 |