Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C-like protease inhibitors

Bioorg Med Chem. 2016 Jul 1;24(13):3035-3042. doi: 10.1016/j.bmc.2016.05.013. Epub 2016 May 12.


Severe acute respiratory syndrome (SARS) led to a life-threatening form of atypical pneumonia in late 2002. Following that, Middle East Respiratory Syndrome (MERS-CoV) has recently emerged, killing about 36% of patients infected globally, mainly in Saudi Arabia and South Korea. Based on a scaffold we reported for inhibiting neuraminidase (NA), we synthesized the analogues and identified compounds with low micromolar inhibitory activity against 3CL(pro) of SARS-CoV and MERS-CoV. Docking studies show that a carboxylate present at either R(1) or R(4) destabilizes the oxyanion hole in the 3CL(pro). Interestingly, 3f, 3g and 3m could inhibit both NA and 3CL(pro) and serve as a starting point to develop broad-spectrum antiviral agents.

Keywords: 3CL(pro); Coronavirus; MERS-CoV; Pyrazolone; SARS-Cov.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Enzyme Activation / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Middle East Respiratory Syndrome Coronavirus* / drug effects
  • Middle East Respiratory Syndrome Coronavirus* / enzymology
  • Models, Molecular
  • Molecular Docking Simulation
  • Peptide Hydrolases / chemistry
  • Peptide Hydrolases / metabolism*
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Severe acute respiratory syndrome-related coronavirus* / drug effects
  • Severe acute respiratory syndrome-related coronavirus* / enzymology


  • Antiviral Agents
  • Protease Inhibitors
  • Peptide Hydrolases