Virtual screening and molecular simulation study of natural products database for lead identification of novel coronavirus main protease inhibitors.

Journal of Biomolecular Structure & Dynamics
Nancy TripathiShreyans K Jain

Abstract

3CL like protease (3CLpro or Mpro) is one of the main proteases of 2019-nCoV. The 3CLpro is a nonstructural protein of SARS-CoV and has an essential role in viral replication and transcription, thus, could be a potential target for anti-SARS drug development. The present study employed ligand- and structure-based approaches to identify the potent inhibitors of 2019-nCoV protease. The e-pharmacophore developed from 3CLpro-1 yielded virtual hits, that were subjected through drug likeliness and PAINS filters to remove interfering compounds. Further comprehensive docking studies, free energy calculations and ADMET studies resulted in two virtual leads- MolPort-000-410-348 and MolPort-002-530-156. The compounds MolPort-000-410-348 and MolPort-002-530-156 displayed good docking score of -12.09 and -13.38 Kcal/mol and free binding energy of -63.34 ± 2.03 and -61.52 ± 2.24 Kcal/mol, respectively. The compounds also exhibited satisfactory predicted ADMET profile and were subjected to molecular dynamic (MD) studies. The MD simulation produced stable complexes of these ligands with 3CLpro protein and ligand RMSD in acceptable limits. Communicated by Ramaswamy H. Sarma.

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Citations

Jan 21, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Konstantina VougogiannopoulouAlexios-Leandros Skaltsounis
Mar 2, 2021·Physiological Research·Z PaluchE Kmoníčková
Jun 13, 2021·International Journal of Biological Macromolecules·Jaspreet Kaur DhanjalRenu Wadhwa
Feb 9, 2021·Journal of Photochemistry and Photobiology. B, Biology·Sachin Ashok ThoratAnnamalai Muthusamy

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