Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus

J Med Chem. 2007 Aug 23;50(17):4087-95. doi: 10.1021/jm070295s. Epub 2007 Jul 31.

Abstract

In this study, 221 phytocompounds were evaluated for activity against anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) activities using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. Ten diterpenoids (1-10), two sesquiterpenoids (11 and 12), two triterpenoids (13 and 14), five lignoids (15-19), curcumin (20), and reference controls niclosamide (21) and valinomycin (22) were potent inhibitors at concentrations between 3.3 and 10 microM. The concentrations of the 22 compounds to inhibit 50% of Vero E6 cell proliferation (CC50) and viral replication (EC50) were measured. The selective index values (SI = CC50/EC50) of the most potent compounds 1, 5, 6, 8, 14, and 16 were 58, >510, 111, 193, 180, and >667, respectively. Betulinic acid (13) and savinin (16) were competitive inhibitors of SARS-CoV 3CL protease with Ki values = 8.2 +/- 0.7 and 9.1 +/- 2.4 microM, respectively. Our findings suggest that specific abietane-type diterpenoids and lignoids exhibit strong anti-SARS-CoV effects.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Chlorocebus aethiops
  • Coronavirus 3C Proteases
  • Cysteine Endopeptidases / chemistry
  • Lignans / chemistry
  • Models, Molecular
  • Pentacyclic Triterpenes
  • Plants, Medicinal*
  • SARS Virus / drug effects*
  • SARS Virus / enzymology
  • Structure-Activity Relationship
  • Terpenes / chemistry
  • Terpenes / pharmacology*
  • Triterpenes / chemistry
  • Vero Cells
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / chemistry
  • Virus Replication

Substances

  • Lignans
  • Pentacyclic Triterpenes
  • Terpenes
  • Triterpenes
  • Viral Proteins
  • savinin
  • betulinic acid
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases