Structure-based virtual screening against SARS-3CL(pro) to identify novel non-peptidic hits

Bioorg Med Chem. 2008 Apr 1;16(7):4138-49. doi: 10.1016/j.bmc.2008.01.011. Epub 2008 Jan 11.


Severe acute respiratory syndrome is a highly infectious upper respiratory tract disease caused by SARS-CoV, a previously unidentified human coronavirus. SARS-3CL(pro) is a viral cysteine protease critical to the pathogen's life cycle and hence a therapeutic target of importance. The recently elucidated crystal structures of this enzyme provide an opportunity for the discovery of inhibitors through rational drug design. In the current study, Gold docking program was utilized to conduct extensive docking studies against the target crystal structure to develop a robust and predictive docking protocol. The validated docking protocol was used to conduct a structure-based virtual screening of the Asinex Platinum collection. Biological evaluation of a screened selection of compounds was carried out to identify novel inhibitors of the viral protease.

MeSH terms

  • Binding Sites
  • Chemical Phenomena
  • Chemistry, Physical
  • Coronavirus 3C Proteases
  • Crystallography, X-Ray
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / metabolism*
  • Drug Evaluation, Preclinical
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Peptides / chemistry
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology*
  • Severe acute respiratory syndrome-related coronavirus / enzymology*
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism*


  • Ligands
  • Peptides
  • Protease Inhibitors
  • Viral Proteins
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases