title: The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice.
abstract: Iminosugars that are competitive inhibitors of endoplasmic reticulum (ER) α-glucosidases have been demonstrated to have antiviral activity against a diverse set of viruses. A novel iminosugar, UV-4B, has recently been shown to provide protection against lethal infections with dengue and influenza A (H1N1) viruses in mice. In the current study, the breadth of activity of UV-4B against influenza was examined ex vivo and in vivo. Efficacy of UV-4B against influenza A and B viruses was shown in primary human bronchial epithelial cells, a principal target tissue for influenza. Efficacy of UV-4B against influenza A (H1N1 and H3N2 subtypes) and influenza B was demonstrated using multiple lethal mouse models with readouts including mortality and weight loss. Clinical trials are ongoing to demonstrate safety of UV-4B and future studies to evaluate antiviral activity against influenza in humans are planned.
authors.affiliation: Emergent BioSolutions, Gaithersburg, MD 20879, USA. warfieldk@ebsi.com.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Warfield
authors.affiliation: Institute for Antiviral Research, Utah State University, Logan, UT 84322-5600, USA. dale.barnard@usu.edu.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Barnard
authors.affiliation: Integrated Biotherapeutics Inc., Gaithersburg, MD 20878, USA. sven@integratedbiotherapeutics.com.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Enterlein
authors.affiliation: Institute for Antiviral Research, Utah State University, Logan, UT 84322-5600, USA. don.smee@usu.edu.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smee
authors.affiliation: Emergent BioSolutions, Gaithersburg, MD 20879, USA. warfieldk@ebsi.com.
authors.forename: Mansoora
authors.initials: M
authors.lastname: Khaliq
authors.affiliation: Emergent BioSolutions, Gaithersburg, MD 20879, USA. khaliqm@ebsi.com.
authors.forename: Aruna
authors.initials: A
authors.lastname: Sampath
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA. mvcallahan@mgh.harvard.edu.|Unither Virology, LLC, Silver Spring, MD 20910, USA. mvcallahan@mgh.harvard.edu.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Callahan
authors.affiliation: Unither Virology, LLC, Silver Spring, MD 20910, USA. urban_ramstedt@yahoo.com.
authors.forename: Urban
authors.initials: U
authors.lastname: Ramstedt
authors.affiliation: Institute for Antiviral Research, Utah State University, Logan, UT 84322-5600, USA. craig.day@usu.edu.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Day
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001835:Body Weight; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D009981:Influenza B virus / Q000187:drug effects*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D017485:1-Deoxynojirimycin; C000604871:N-9-methoxynonyldeoxynojirimycin
keywords: Iminosugar; UV-4B; antiviral; human bronchial epithelial cells; influenza; mice