Derivatives of usnic acid inhibit broad range of influenza viruses and protect mice from lethal influenza infection

Antivir Chem Chemother. 2015 Aug;24(3-4):92-8. doi: 10.1177/2040206616636992. Epub 2016 Mar 27.

Abstract

Background: Influenza is a disease of significant morbidity and mortality, the number of anti-influenza drugs is small; many of them stimulate the appearance of resistant strains. In this work, we demonstrate activity of some usnic acid (UA) derivatives against influenza virus in vitro and in vivo.

Methods: Organic synthesis was used to prepare compounds. Antiviral activity of the compounds in vitro was evaluated by their ability to decrease the virus titer on Madin-Darby Canine Kidney cells. In vivo activity was evaluated by decrease of mortality and index of protection.

Results: Compounds were tested against a broad spectrum of influenza virus strains and showed activity against all used strains. One compound, [5] (valine enamine of UA), also significantly reduced lethality of infected animals and does not give rise to the appearance of resistant strains. Additional studies showed that hepatotoxicity of compound [5] is reduced comparatively to UA.

Conclusion: Our results suggest that valine enamine of UA could be a potential candidate for the development of a new anti-influenza therapy.

Keywords: Compounds; influenza; inhibitors; orthomyxoviridae; respiratory infections.

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Benzofurans / administration & dosage
  • Benzofurans / pharmacology*
  • Cell Survival / drug effects
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Hepatocytes / drug effects
  • Hepatocytes / pathology
  • Madin Darby Canine Kidney Cells / drug effects
  • Madin Darby Canine Kidney Cells / virology
  • Mice
  • Mice, Inbred Strains
  • Microbial Sensitivity Tests
  • Orthomyxoviridae / drug effects*
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / virology*
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Benzofurans
  • usnic acid