Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARS-CoV

J Enzyme Inhib Med Chem. 2016;31(1):23-30. doi: 10.3109/14756366.2014.1003215. Epub 2015 Feb 16.

Abstract

Two viral proteases of severe acute respiratory syndrome coronavirus (SARS-CoV), a chymotrypsin-like protease (3CL(pro)) and a papain-like protease (PL(pro)) are attractive targets for the development of anti-SARS drugs. In this study, nine alkylated chalcones (1-9) and four coumarins (10-13) were isolated from Angelica keiskei, and the inhibitory activities of these constituents against SARS-CoV proteases (3CL(pro) and PL(pro)) were determined (cell-free/based). Of the isolated alkylated chalcones, chalcone 6, containing the perhydroxyl group, exhibited the most potent 3CL(pro) and PL(pro) inhibitory activity with IC50 values of 11.4 and 1.2 µM. Our detailed protein-inhibitor mechanistic analysis of these species indicated that the chalcones exhibited competitive inhibition characteristics to the SARS-CoV 3CL(pro), whereas noncompetitive inhibition was observed with the SARS-CoV PL(pro).

Keywords: 3CLpro; Angelica keiskei; PLpro; SARS-CoV; chalcone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angelica / chemistry*
  • Antiviral Agents / chemistry
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Chalcones / chemistry
  • Chalcones / isolation & purification*
  • Chalcones / pharmacology*
  • Cysteine Proteases / metabolism*
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / isolation & purification
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Severe acute respiratory syndrome-related coronavirus / drug effects
  • Severe acute respiratory syndrome-related coronavirus / enzymology*
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Chalcones
  • Cysteine Proteinase Inhibitors
  • Cysteine Proteases