title: Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.
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.
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
authors.forename: Olivia
authors.initials: O
authors.lastname: Perwitasari
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
authors.forename: Emery
authors.initials: E
authors.lastname: Register
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
authors.forename: Jackelyn
authors.initials: J
authors.lastname: Crabtree
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
authors.forename: Jon
authors.initials: J
authors.lastname: Gabbard
authors.affiliation: Department of Pathology, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Howerth
authors.affiliation: Karyopharm Therapeutics, Newton, Massachusetts, United States of America.
authors.forename: Sharon
authors.initials: S
authors.lastname: Shacham
authors.affiliation: Karyopharm Therapeutics, Newton, Massachusetts, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Carlson
authors.affiliation: Karyopharm Therapeutics, Newton, Massachusetts, United States of America.
authors.forename: Sharon
authors.initials: S
authors.lastname: Tamir
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, United States of America.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D000178:Acrylamides / Q000627:therapeutic use*; D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D006834:Hydrazines / Q000627:therapeutic use*; D009980:Influenza A virus / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology; D014779:Virus Replication / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects; D014230:Triazoles
chemical_list: D000178:Acrylamides; D000998:Antiviral Agents; D006834:Hydrazines; C000593855:verdinexor; D014230:Triazoles