Molecular insights on bioactive compounds againstCovid-19: A Network pharmacological and computational study.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Current computer-aided drug design Pub Date : 2022-09-14 DOI:10.2174/1573409918666220914092145

Jayanth Jeevanandam, Esackimuthu Paramasivam, Anbumathi Palanisamy, Srikanth Ragavendran, Saraswathi Nambiappan Thangavel

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引用次数: 0

Abstract

Background: Network pharmacology based identification of phytochemicals in the form of cocktails against off-targets can play a significant role in inhibition of SARS_CoV2 viral entry and its propagation. This study includes network pharmacology, virtual screening, docking and molecular dynamics to investigate the distinct antiviral mechanisms of effective phytochemicals against SARS_CoV2.

Methods: SARS_CoV2 human-protein interaction network was explored from the BioGRID database and analysed using Cytoscape. Further analysis was performed to explore biological function, protein-phytochemical/drugs network and up-down regulation of pathological host target proteins. This lead to understand the antiviral mechanism of phytochemicals against SARS_CoV2. The network was explored through g:Profiler, EnrichR, CTD, SwissTarget, STITCH, DrugBank, BindingDB, STRING and SuperPred. Virtual screening of phytochemicals against potential antiviral targets such as M-Pro, NSP1, Receptor binding domain, RNA binding domain, and ACE2 discloses the effective interaction between them. Further, the binding energy calculations through simulation of the docked complex explains the efficiency and stability of the interactions.

Results: The network analysis identified quercetin, genistein, luteolin, eugenol, berberine, isorhamnetin and cinnamaldehyde to be interacting with host proteins ACE2, DPP4, COMT, TUBGCP3, CENPF, BRD2 and HMOX1 which are involved in antiviral mechanisms such as viral entry, viral replication, host immune response, and antioxidant activity. Thus indicating that herbal cocktails can effectively tackle the viral hijacking of the crucial biological functions of human host. Further exploration through Virtual screening, docking and molecular dynamics recognizes the effective interaction of phytochemicals such as punicalagin, scutellarin, and solamargine with their respective potential targets.

Conclusion: This work illustrates probable strategy for identification of phytochemical based cocktails and off-targets which are effective against SARS_CoV 2.

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针对 Covid-19 的生物活性化合物的分子见解：网络药理学和计算研究

背景：以网络药理学为基础，以鸡尾酒形式鉴定针对非靶点的植物化学物质，可在抑制SARS_CoV2病毒进入和传播方面发挥重要作用。这项研究包括网络药理学、虚拟筛选、对接和分子动力学，以研究有效的植物化学物质对 SARS_CoV2 的不同抗病毒机制：方法：从 BioGRID 数据库中探索 SARS_CoV2 人-蛋白相互作用网络，并使用 Cytoscape 进行分析。方法：从 BioGRID 数据库中探索了 SARS_CoV2 的人-蛋白相互作用网络，并使用 Cytoscape 进行了分析，进一步分析了生物功能、蛋白-植物化学物/药物网络以及病理宿主靶蛋白的上下调节。这有助于了解植物化学物质对 SARS_CoV2 的抗病毒机制。该网络通过 g:Profiler、EnrichR、CTD、SwissTarget、STITCH、DrugBank、BindingDB、STRING 和 SuperPred 进行了探索。针对潜在的抗病毒靶标，如 M-Pro、NSP1、受体结合域、RNA 结合域和 ACE2，对植物化学物质进行虚拟筛选，发现它们之间存在有效的相互作用。此外，通过模拟对接复合物的结合能计算，解释了相互作用的效率和稳定性：网络分析发现槲皮素、染料木素、木犀草素、丁香酚、小檗碱、异鼠李素和肉桂醛与宿主蛋白 ACE2、DPP4、COMT、TUBGCP3、CENPF、BRD2 和 HMOX1 相互作用，这些蛋白参与了病毒进入、病毒复制、宿主免疫反应和抗氧化活性等抗病毒机制。这表明草药鸡尾酒能有效解决病毒劫持人体宿主关键生物功能的问题。通过虚拟筛选、对接和分子动力学等方法进行的进一步探索，确认了植物化学物质（如 punicalagin、scutellarin 和 solamargine）与各自潜在靶点之间的有效相互作用：这项工作说明了鉴定植物化学物质鸡尾酒和有效抗击 SARS_CoV 2 的非靶点的可能策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current computer-aided drug design 医学-计算机：跨学科应用

CiteScore

3.70

自引率

5.90%

发文量

审稿时长

>12 weeks

期刊介绍： Aims & Scope Current Computer-Aided Drug Design aims to publish all the latest developments in drug design based on computational techniques. The field of computer-aided drug design has had extensive impact in the area of drug design. Current Computer-Aided Drug Design is an essential journal for all medicinal chemists who wish to be kept informed and up-to-date with all the latest and important developments in computer-aided methodologies and their applications in drug discovery. Each issue contains a series of timely, in-depth reviews, original research articles and letter articles written by leaders in the field, covering a range of computational techniques for drug design, screening, ADME studies, theoretical chemistry; computational chemistry; computer and molecular graphics; molecular modeling; protein engineering; drug design; expert systems; general structure-property relationships; molecular dynamics; chemical database development and usage etc., providing excellent rationales for drug development.