Publication: Virtual screening and molecular simulation study of natural products database for lead identification of novel coronavirus main protease inhibitors
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Date
2022
Journal Title
Journal of Biomolecular Structure and Dynamics
Journal ISSN
Volume Title
Publisher
Taylor and Francis Ltd.
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. � 2020 Informa UK Limited, trading as Taylor & Francis Group.
Description
Keywords
COVID-19, molecular docking, natural products, protease inhibitors, virtual screening