Halogenated Chrysins Inhibit Dengue and Zika Virus Infectivity

Sci Rep. 2017 Oct 20;7(1):13696. doi: 10.1038/s41598-017-14121-5.

Abstract

Dengue virus infection is a global threat for which no specific treatment has not been established. Previous reports suggested chrysin and flavanone derivatives were potential flaviviral inhibitors. Here, we reported two halogenated chrysins, abbreviated FV13 and FV14, were highly potent against DENV1-4 and ZIKV infectivities with the FV13 EC50 values of 2.30 ± 1.04, 1.47 ± 0.86, 2.32 ± 1.46, 1.78 ± 0.72 and 1.65 ± 0.86 µM; and FV14 EC50 values of 2.30 ± 0.92, 2.19 ± 0.31, 1.02 ± 0.31, 1.29 ± 0.60 and 1.39 ± 0.11 µM, respectively. The CC50s to LLC/MK2 of FV13 and FV14 were 44.28 ± 2.90 μM, 42.51 ± 2.53 µM, respectively. Mechanism of drug action studies suggested multiple targets but maximal efficiency was achieved with early post infection treatment. This is the first report showing a high potency of halogenated chrysins for development as a broad-spectrum anti-flaviviral drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Dengue / drug therapy*
  • Dengue Virus / drug effects
  • Dose-Response Relationship, Drug
  • Flavones / chemistry
  • Flavones / pharmacology*
  • Humans
  • Macaca mulatta
  • Molecular Structure
  • Zika Virus / drug effects
  • Zika Virus Infection / drug therapy*

Substances

  • Antiviral Agents
  • Flavones