文章基本信息

标题：Computational studies on potential new anti-Covid-19 agents with a multi-target mode of action
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作者：Ranjan K. Mohapatra ; Mohammad Azam ; Pranab K. Mohapatra 等
期刊名称：Journal of King Saud University - Science
印刷版ISSN：1018-3647
出版年度：2022
卷号：34
期号：5
页码：1-8
DOI：10.1016/j.jksus.2022.102086
语种：English
出版社：Elsevier
摘要：AbstractA compound that could inhibit multiple targets associated with SARS-CoV-2 infection would prove to be a drug of choice against the virus. Human receptor-ACE2, receptor binding domain (RBD) of SARS-CoV-2 S-protein, Papain-like protein of SARS-CoV-2 (PLpro), reverse transcriptase of SARS-CoV-2(RdRp) were chosen for in silico study. A set of previously synthesized compounds (1–5) were docked into the active sites of the targets. Based on the docking score, ligand efficiency, binding free energy, and dissociation constants for a definite conformational position of the ligand, inhibitory potentials of the compounds were measured. The stability of the protein–ligand (P-L) complex was validatedin silicoby using molecular dynamics simulations using the YASARA suit. Moreover, the pharmacokinetic properties, FMO and NBO analysis were performed for ranking the potentiality of the compounds as drug. The geometry optimizations and electronic structures were investigated using DFT. As per the study, compound-5has the best binding affinity against all four targets. Moreover, compounds 1, 3 and 5 are less toxic and can be considered for oral consumption.
关键词：KeywordsMolecular electrostatic potentialFrontiers molecular orbitalNatural bond orbitalMolecular dockingMolecular dynamicsPharmacokineticsDrug-likeness predictionSARS-CoV-2