Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13

Bioorg Med Chem Lett. 2012 Jun 15;22(12):4049-54. doi: 10.1016/j.bmcl.2012.04.081. Epub 2012 Apr 25.

Abstract

Severe acute respiratory syndrome (SARS) is an infectious disease with a strong potential for transmission upon close personal contact and is caused by the SARS-coronavirus (CoV). However, there are no natural or synthetic compounds currently available that can inhibit SARS-CoV. We examined the inhibitory effects of 64 purified natural compounds against the activity of SARS helicase, nsP13, and the hepatitis C virus (HCV) helicase, NS3h, by conducting fluorescence resonance energy transfer (FRET)-based double-strand (ds) DNA unwinding assay or by using a colorimetry-based ATP hydrolysis assay. While none of the compounds, examined in our study inhibited the DNA unwinding activity or ATPase activity of human HCV helicase protein, we found that myricetin and scutellarein potently inhibit the SARS-CoV helicase protein in vitro by affecting the ATPase activity, but not the unwinding activity, nsP13. In addition, we observed that myricetin and scutellarein did not exhibit cytotoxicity against normal breast epithelial MCF10A cells. Our study demonstrates for the first time that selected naturally-occurring flavonoids, including myricetin and scultellarein might serve as SARS-CoV chemical inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Apigenin / chemistry
  • Apigenin / pharmacology*
  • Breast / cytology
  • Breast / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Colorimetry
  • DNA / chemistry
  • DNA Helicases / antagonists & inhibitors*
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Female
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Fluorescence Resonance Energy Transfer
  • Hepacivirus / drug effects
  • Hepacivirus / enzymology
  • Humans
  • Hydrolysis
  • Inhibitory Concentration 50
  • Kinetics
  • Methyltransferases / antagonists & inhibitors*
  • RNA Helicases
  • SARS Virus / drug effects*
  • SARS Virus / enzymology
  • Species Specificity
  • Viral Nonstructural Proteins
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • Flavonoids
  • Viral Nonstructural Proteins
  • Viral Proteins
  • myricetin
  • Apigenin
  • Adenosine Triphosphate
  • DNA
  • Methyltransferases
  • Nsp13 protein, SARS-CoV
  • DNA Helicases
  • RNA Helicases
  • scutellarein