📄 Discovering severe acute respiratory syndrome coronavirus 3CL protease inhibitors: Virtual screening, surface plasmon resonance, and fluorescence resonance energy transfer assays

An integrated system has been developed for discovering potent inhibitors of severe acute respiratory syndrome coronavirus 3C-like protease (SARS-CoV 3CL pro) 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 3CL pro. The enzymatic inhibition activities of these 52 SARS-CoV 3CL pro binders were further applied to FRET-based assay, and IC 50 values were determined. Based on this integrated assay platform, 8 new SARS-CoV 3CL pro inhibitors were discovered. The fact that the obtained IC 50 values for the inhibitors are in good accordance with the discovered dissociation equilibrium constants (K Ds) 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 3CL pro inhibitors, and the determined inhibitors could be used as possible lead compounds for further research. © 2006 Society for Biomolecular Sciences.

keywords 🔗 severe acute (1373) 🔗 syndrome coronavirus (1074) 🔗 resonance energy (16) 🔗 plasmon resonance (20) 🔗 respiratory syndrome (2004) 🔗 acute respiratory (1734) 🔗 energy transfer (19)

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