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

Abstract

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.

Network pharmacology combined with GEO database identifying the mechanisms and molecular targets of Polygoni Cuspidati Rhizoma on Peri-implants

“…Go enrichment analysis was carried out with the function of "Enrichment go". KEGG enrichment analysis carried the enrich-KEGG function and the database was KEGG database ( https://www.kegg.Jp/ 33 . For parameters of both species was HAS and filter values (P and Q values) are set to 0.05.…”

Cucumis sativus L. Seeds Ameliorate Muscular Spasm-Induced Gastrointestinal and Respiratory Disorders by Simultaneously Inhibiting Calcium Mediated Signaling Pathway

“…The bioactive compounds (stigmasterol, β-sitosterol, scopoletin, 1,4-dicaffeoylquinic acid, luteolin, kaempferol, ferulic acid, epicatechin, ellagic acid, kaempferol-3-o-glucoside, quercetin, apigenin) of C. sativus seeds EtOH extract previously identified through LC ESI-MS/MS and quantified with HPLC were subjected for absorption, distribution, metabolism excretion and toxicity (ADMET) in Qikprop module of Maestro (Schrodinger suite 2015), SWISS ADME (http://www.swissadme.ch, accessed on: 10 July 2021) and pkCSM (http:// biosig.unimelb.edu.au/pkcsm/prediction, accessed on: 10 July 2021) to evaluate ADMET and drug-likeness parameters [28].…”

“…Lipinski and other parameters were studied for drug-likeness of compounds, but most compounds could not pass these drug-likeness filters sufficiently. Lipinski's rule of five and other parameters are not considered rigid standards because FDA approved most natural products and semisynthetic derivatives that cannot fit with these parameters [27,28].…”

Systematic virtual screening in search of SARS CoV-2 inhibitors against spike glycoprotein: pharmacophore screening, molecular docking, ADMET analysis and MD simulations

“…The use of computational studies has promoted the design and discovery of new chemicals scaffolds acting against the choice of drug targets through molecular modelling techniques like molecular docking, ADMET analysis and molecular dynamics (MD) simulation [ 32 ]. Recently, we have reported the virtual screening of small molecules against RdRp [ 33 ] and Mpro [ 34 ] using molecular docking, ADMET analysis and MD simulations. In continuation towards our endeavour for search of SARS CoV-2 inhibitors, we become interested for the in silico-based virtual screening of 175,851 ligands of Asinex BioDesign library considering the massive demand for SARS CoV-2 inhibitors having good binding affinity towards the spike glycoprotein.…”