Discovery of a novel HCV helicase inhibitor by a de novo drug design approach

Bioorg Med Chem Lett. 2009 Jun 1;19(11):2935-7. doi: 10.1016/j.bmcl.2009.04.074. Epub 2009 Apr 22.


Herein we report a successful application of a computer-aided design approach to identify a novel HCV helicase inhibitor. A de novo drug design methodology was used to generate an initial set of structures that could potentially bind to a putative binding site. Further structure refinement was carried out through docking a series of focused virtual libraries. The most promising compound was synthesised and it exhibited a submicromolar inhibition of the HCV helicase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Binding Sites
  • Computer Simulation
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Hepacivirus / enzymology*
  • RNA Helicases / antagonists & inhibitors*
  • RNA Helicases / metabolism
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism


  • Antiviral Agents
  • Enzyme Inhibitors
  • NS3 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • RNA Helicases