In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis.

In search of RdRp and Mpro inhibitors against SARS CoV-2: Molecular docking, molecular dynamic simulations and ADMET analysis.

Normi D Gajjar, Tejas M Dhameliya, Gaurang B Shah

Corona Virus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus (SARS CoV-2) has been declared a worldwide pandemic by WHO recently. The complete understanding of the complex genomic structure of SARS CoV-2 has enabled the use of computational tools in search of SARS CoV-2 inhibitors against the multiple proteins responsible for its entry and multiplication in human cells. With this endeavor, 177 natural, anti-viral chemical entities and their derivatives, selected through the critical analysis of the literatures, were studied using pharmacophore screening followed by molecular docking against RNA dependent RNA polymerase and main protease. The identified hits have been subjected to molecular dynamic simulations to study the stability of ligand-protein complexes followed by ADMET analysis and Lipinski filters to confirm their drug likeliness. It has led to an important start point in the drug discovery and development of therapeutic agents against SARS CoV-2.

2021

molecular docking, SARS-CoV-2, ACE-angiotensin-converting enzyme, Mpro, RdRp, Natural products, MD simulation, COVID-19 (coronavirus disease 2019), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), WHO, World health organization, Mpro, main protease, RMSD, root mean square deviation, RMSF, root mean square fluctuation, SASA, solvent accessible surface area, NSP, non-structural protein, RdRp, RNA-dependent RNA polymerase, ADMET, Absorption, Distribution, Metabolism, Excretion and Toxicity, 3CLpro, 3-chymotrypsin-like protease, ASL, Atom specification language, Dscore, Druggability score, EM, Electron microscopy, HB, Hydrogen bond, MD simulation, Molecular dynamic simulation, PLpro, Papain-like protease, RoG, Radius of gyration, SP, Standard precision

10.1016/j.molstruc.2021.130488

Journal of molecular structure