Discordant Activity of Kaempferol Towards Dengue Virus and Japanese Encephalitis Virus

Molecules. 2020 Mar 10;25(5):1246. doi: 10.3390/molecules25051246.

Abstract

Kaempferol, a plant-derived flavonoid, has been reported to have activity against Japanese encephalitis virus (JEV) in BHK-21 cells. To determine the broader utility of this compound, we initially evaluated the activity of kaempferol against JEV and dengue virus (DENV) in HEK293T/17 cells. Results showed no significant antiviral activity against either virus. We subsequently investigated the activity of kaempferol against both JEV and DENV in BHK-21 cells. Results showed a significant inhibition of JEV infection but, surprisingly, a significant enhancement of DENV infection. The effect of kaempferol on both host protein expression and transcription was investigated and both transcriptional and translational inhibitory effects were observed, although a more marked effect was observed on host cell protein expression. Markedly, while GRP78 was increased in DENV infected cells treated with kaempferol, it was not increased in JEV infected cells treated with kaempferol. These results show that cellular alteration induced by one compound can have opposite effects on viruses from the same family, suggesting the presence of distinct replication strategies for these two viruses.

Keywords: Japanese encephalitis virus; Kaempferol; antiviral activity; dengue virus.

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • Dengue / drug therapy
  • Dengue / genetics
  • Dengue Virus / drug effects*
  • Encephalitis Virus, Japanese / drug effects*
  • Encephalitis, Japanese / drug therapy
  • Encephalitis, Japanese / genetics
  • Endoplasmic Reticulum Chaperone BiP
  • HEK293 Cells
  • Heat-Shock Proteins / genetics
  • Humans
  • Kaempferols / pharmacology*
  • Protein Biosynthesis / drug effects
  • Transcription, Genetic / drug effects
  • Virus Replication / drug effects

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Kaempferols
  • kaempferol