An integrated system has been developed for discovering potent inhibitors of severe acute respiratory syndrome coronavirus
3CClike protease (SARS-CoV 3CLpro) by virtual screening correlating with surface plasmon resonance (SPR) and fluorescence
resonance energy transfer (FRET) technologies-based assays. The authors screened 81,287 small molecular compounds
against SPECS database by virtual screening; 256 compounds were subsequently selected for biological evaluation.
Through SPR technology-based assay, 52 from these 256 compounds were discovered to show binding to SARS-CoV 3CLpro.
The enzymatic inhibition activities of these 52 SARS-CoV 3CLpro binders were further applied to FRET-based assay, and
IC50 values were determined. Based on this integrated assay platform, 8 new SARS-CoV 3CLpro inhibitors were discovered.
The fact that the obtained IC50 values for the inhibitors are in good accordance with the discovered dissociation equilibrium
constants (KDs) assayed by SPR implied the reliability of this platform. Our current work is hoped to supply a powerful
approach in the discovery of potent SARS-CoV 3CLpro inhibitors, and the determined inhibitors could be used as possible
lead compounds for further research.