Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we...

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Main Authors: Olivia Perwitasari, Scott Johnson, Xiuzhen Yan, Emery Register, Jackelyn Crabtree, Jon Gabbard, Elizabeth Howerth, Sharon Shacham, Robert Carlson, Sharon Tamir, Ralph A Tripp
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5125695?pdf=render
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author Olivia Perwitasari
Scott Johnson
Xiuzhen Yan
Emery Register
Jackelyn Crabtree
Jon Gabbard
Elizabeth Howerth
Sharon Shacham
Robert Carlson
Sharon Tamir
Ralph A Tripp
author_facet Olivia Perwitasari
Scott Johnson
Xiuzhen Yan
Emery Register
Jackelyn Crabtree
Jon Gabbard
Elizabeth Howerth
Sharon Shacham
Robert Carlson
Sharon Tamir
Ralph A Tripp
author_sort Olivia Perwitasari
collection DOAJ
description Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.
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spelling doaj.art-bdbea100a7b54b728eb4ce648327d8922022-12-22T01:38:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011111e016722110.1371/journal.pone.0167221Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.Olivia PerwitasariScott JohnsonXiuzhen YanEmery RegisterJackelyn CrabtreeJon GabbardElizabeth HowerthSharon ShachamRobert CarlsonSharon TamirRalph A TrippInfluenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.http://europepmc.org/articles/PMC5125695?pdf=render
spellingShingle Olivia Perwitasari
Scott Johnson
Xiuzhen Yan
Emery Register
Jackelyn Crabtree
Jon Gabbard
Elizabeth Howerth
Sharon Shacham
Robert Carlson
Sharon Tamir
Ralph A Tripp
Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.
PLoS ONE
title Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.
title_full Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.
title_fullStr Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.
title_full_unstemmed Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.
title_short Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.
title_sort antiviral efficacy of verdinexor in vivo in two animal models of influenza a virus infection
url http://europepmc.org/articles/PMC5125695?pdf=render
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