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PLoS One. 2016 Nov 28;11(11):e0167221. doi: 10.1371/journal.pone.0167221. eCollection 2016.

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

Author information

1
Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
2
Department of Pathology, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
3
Karyopharm Therapeutics, Newton, Massachusetts, United States of America.

Abstract

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.

PMID:
27893810
PMCID:
PMC5125695
DOI:
10.1371/journal.pone.0167221
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: SS and ST are current employees and shareholders of Karyopharm Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors have declared that no competing interests exist.

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