Computational Search for Potential COVID-19 Drugs from Ayurvedic Medicinal Plants to Identify Potential Inhibitors against SARS-CoV-2 Targets.

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Current computer-aided drug design Pub Date : 2023-01-01 DOI:10.2174/1573409919666221117145404

V Alagarsamy, V Raja Solomon, P Shyam Sundar, V S Kulkarni, M T Sulthana, A Dharshini Aishwarya, B Narendhar, S Murugesan

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引用次数: 1

Abstract

Background: To date, very few small drug molecules are used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been discovered since the epidemic commenced in November 2019. SARS-CoV-2 RdRp and spike protein are essential targets for drug development amidst whole variants of coronaviruses.

Objective: This study aims to discover and recognize the most effective and promising small molecules against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and spike protein targets through molecular docking screening of 39 phytochemicals from five different Ayurveda medicinal plants.

Methods: The phytochemicals were downloaded from PubChem, and SARS-CoV-2 RdRp and spike protein were taken from the protein data bank. The molecular interactions, binding energy, and ADMET properties were analyzed.

Results: Molecular docking analysis identified some phytochemicals, oleanolic acid, friedelin, serratagenic acid, uncinatone, clemaphenol A, sennosides B, trilobine and isotrilobine from ayurvedic medicinal plants possessing greater affinity against SARS-CoV-2-RdRp and spike protein targets. Two molecules, namely oleanolic acid and sennosides B, with low binding energies, were the most promising. Furthermore, based on the docking score, we carried out MD simulations for the oleanolic acid and sennosides B-protein complexes.

Conclusion: Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike protein of SARS-CoV-2.

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阿育吠陀药用植物中潜在COVID-19药物的计算搜索，以确定针对SARS-CoV-2靶点的潜在抑制剂

背景:自2019年11月疫情开始以来，迄今为止，用于治疗严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)的小分子药物很少。SARS-CoV-2 RdRp和刺突蛋白是冠状病毒全变异中药物开发的重要靶点。目的:通过对来自5种不同阿育吠达药用植物的39种植物化学物质的分子对接筛选，发现和识别抗SARS-CoV-2 RNA依赖性RNA聚合酶(RdRp)和刺突蛋白靶点最有效和最有前景的小分子。方法:从PubChem网站下载植物化学物质，从蛋白质数据库中提取SARS-CoV-2 RdRp和刺突蛋白。分析了分子间相互作用、结合能和ADMET性质。结果:通过分子对接分析，从阿育vedic药用植物中鉴定出对SARS-CoV-2-RdRp和刺突蛋白靶点具有较强亲和力的植物化学物质，齐果酸、毛瑞林、锯齿原酸、钩叶酮、clemaphenol A、sennosides B、trilobine和异trilobine。齐墩果酸和sennosides B这两个结合能较低的分子是最有希望的。此外，基于对接得分，我们对齐墩果酸和sen皂苷b蛋白复合物进行了MD模拟。结论:分子ADMET谱分析表明对接的植物化学物质是安全的。本研究提示药用植物活性化学物质可抑制SARS-CoV-2的RdRp和刺突蛋白。

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.