An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy

J Med Chem. 2016 Jul 28;59(14):6595-628. doi: 10.1021/acs.jmedchem.5b01461. Epub 2016 Feb 29.


Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus that infected more than 8000 individuals and resulted in more than 800 (10-15%) fatalities in 2003. The causative agent of SARS has been identified as a novel human coronavirus (SARS-CoV), and its viral protease, SARS-CoV 3CL(pro), has been shown to be essential for replication and has hence been recognized as a potent drug target for SARS infection. Currently, there is no effective treatment for this epidemic despite the intensive research that has been undertaken since 2003 (over 3500 publications). This perspective focuses on the status of various efficacious anti-SARS-CoV 3CL(pro) chemotherapies discovered during the last 12 years (2003-2015) from all sources, including laboratory synthetic methods, natural products, and virtual screening. We describe here mainly peptidomimetic and small molecule inhibitors of SARS-CoV 3CL(pro). Attempts have been made to provide a complete description of the structural features and binding modes of these inhibitors under many conditions.

Publication types

  • Review

MeSH terms

  • Animals
  • Coronavirus 3C Proteases
  • Cysteine Endopeptidases / metabolism
  • Humans
  • Molecular Conformation
  • Peptidomimetics / chemistry
  • Peptidomimetics / pharmacology*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / metabolism


  • Peptidomimetics
  • Protease Inhibitors
  • Small Molecule Libraries
  • Viral Proteins
  • Cysteine Endopeptidases
  • Coronavirus 3C Proteases