Hirsutine, an indole alkaloid of uncaria rhynchophylla, inhibits late step in dengue virus lifecycle

Takayuki Hishiki*, Fumihiro Kato, Shigeru Tajima, Kazufumi Toume, Masahito Umezaki, Tomohiko Takasaki, Tomoyuki Miura

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Dengue virus (DENV) is transmitted to humans by Aedes mosquitoes and is a public health issue worldwide. No antiviral drugs specific for treating dengue infection are currently available. To identify novel DENV inhibitors, we analyzed a library of 95 compounds and 120 extracts derived from crude drugs (herbal medicines). In the primary screening, A549 cells infected with DENV-1 were cultured in the presence of each compound and extract at a final concentration of 10 µM (compound) and 100 µg/mL (extract), and reduction of viral focus formation was assessed. Next, we eliminated compounds and extracts which were cytotoxic using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hirsutine, an indole alkaloid of Uncaria rhynchophylla, was identified as a potent anti-DENV compound exhibiting high efficacy and low cytotoxicity. Hirsutine showed antiviral activity against all DENV serotypes. Time-of-drug-addition and time-of-drug-elimination assays indicated that hirsutine inhibits the viral particle assembly, budding, or release step but not the viral translation and replication steps in the DENV lifecycle. A subgenomic replicon system was used to confirm that hirsutine does not restrict viral genome RNA replication. Hirsutine is a novel DENV inhibitor and potential candidate for treating dengue fever.

Original languageEnglish
Article number1674
JournalFrontiers in Microbiology
Volume8
Issue numberAUG
DOIs
StatePublished - 2017/08/30

Keywords

  • Alkaloid
  • Antiviral
  • Crude drug
  • Dengue virus
  • Focus assay
  • Herbal medicine
  • Hirsutine
  • Replicon

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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