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

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. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

A worldwide pandemic of COVID-19 caused by SARS CoV-2 has prompted the search for inhibitors using computational tools. By screening natural anti-viral compounds and their derivatives, researchers have identified potential therapeutic agents against SARS CoV-2 through molecular docking and dynamic simulations, providing a promising start for drug discovery and development.