Dieckol, a SARS-CoV 3CL(pro) Inhibitor, Isolated From the Edible Brown Algae Ecklonia Cava

Bioorg Med Chem. 2013 Jul 1;21(13):3730-7. doi: 10.1016/j.bmc.2013.04.026. Epub 2013 Apr 22.

Abstract

SARS-CoV 3CL(pro) plays an important role in viral replication. In this study, we performed a biological evaluation on nine phlorotannins isolated from the edible brown algae Ecklonia cava. The nine isolated phlorotannins (1-9), except phloroglucinol (1), possessed SARS-CoV 3CL(pro) inhibitory activities in a dose-dependently and competitive manner. Of these phlorotannins (1-9), two eckol groups with a diphenyl ether linked dieckol (8) showed the most potent SARS-CoV 3CL(pro) trans/cis-cleavage inhibitory effects (IC(50)s = 2.7 and 68.1 μM, respectively). This is the first report of a (8) phlorotannin chemotype significantly blocking the cleavage of SARS-CoV 3CL(pro) in a cell-based assay with no toxicity. Furthermore, dieckol (8) exhibited a high association rate in the SPR sensorgram and formed extremely strong hydrogen bonds to the catalytic dyad (Cys145 and His41) of the SARS-CoV 3CL(pro).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry*
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology
  • Benzofurans / chemistry*
  • Benzofurans / isolation & purification
  • Benzofurans / pharmacology
  • Cysteine Proteases / metabolism
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / isolation & purification
  • Cysteine Proteinase Inhibitors / pharmacology
  • Humans
  • Molecular Docking Simulation
  • Phaeophyta / chemistry*
  • Quantitative Structure-Activity Relationship
  • SARS Virus / drug effects
  • SARS Virus / enzymology*
  • Severe Acute Respiratory Syndrome / drug therapy

Substances

  • Antiviral Agents
  • Benzofurans
  • Cysteine Proteinase Inhibitors
  • dieckol
  • Cysteine Proteases