The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice

Viruses. 2016 Mar 7;8(3):71. doi: 10.3390/v8030071.

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.

Keywords: Iminosugar; UV-4B; antiviral; human bronchial epithelial cells; influenza; mice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 1-Deoxynojirimycin / administration & dosage
  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / pharmacology
  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacology
  • Body Weight
  • Cells, Cultured
  • Disease Models, Animal
  • Epithelial Cells / virology
  • Humans
  • Influenza A virus / drug effects*
  • Influenza B virus / drug effects*
  • Mice
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antiviral Agents
  • 1-Deoxynojirimycin
  • N-9-methoxynonyldeoxynojirimycin