板蓝根生物碱有望成为抗新冠肺炎的候选药物:用于药物开发的分子对接模拟

IF 0.7 Q4 PHARMACOLOGY & PHARMACY
Farnoosh Kazemi, M. Mojarrab, G. Bahrami, S. Miraghaei, Saba Hadidi, M. Majnooni
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引用次数: 0

摘要

背景:由于严重急性呼吸系统综合征冠状病毒2型的复杂性,针对这种高流行率的致命疾病的有效药物治疗方案尚未获得批准。本研究旨在探索板蓝根的主要生物碱对严重急性呼吸系统综合征冠状病毒2型靶标的有效性,板蓝根是生物碱最丰富的植物来源之一。材料和方法:靶蛋白的三维结构,包括3CLpro;PLpro和RdRp是从蛋白质数据库下载的。配体的结构从PubChem数据库中检索或通过ORCA程序进行优化。选择利托那韦、洛匹那韦、索福布韦和瑞德西韦作为对照抑制剂。通过AutoDock Vina选项进行对接计算,并通过Gromacs 5.1.4模拟包对排名靠前的化合物进行分子动力学模拟。结果:与其他酶相比,15个化合物与PLpro的相互作用更强。二羟基亚丙基水杨酸A以最高的亲和力(-9.3 kcal/mol)与PLpro的活性位点结合,这甚至超过了利托那韦和洛匹那韦的结合常数。在这15个化合物中,二羟基亚丙基水杨酸A和Isatibsinodosulfonic acid B与3CLpro的结合倾向最高。二羟基丙亚丙基水杨酸A、Indirubin、Insatindibisindolamide A、Indigo、InsatinDibindolamide B、Isatibidinosulfonic acid B和Isatindosulfonic cid acid B具有最高的RdRp结合亲和力,甚至更多的是Remdesivir。结论:根据结果,二羟基亚丙基水杨酸A和表甲状腺肿素与所有三种酶的相互作用分别最高和最弱。基于这些发现,二羟基丙亚丙基satistine A可能是对抗严重急性呼吸系统综合征冠状病毒2型的潜在候选治疗药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The alkaloids of Isatis indigotica as promising candidates against COVID-19: A molecular docking simulation for drug development
Background: Due to the complexities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective medicinal treatment protocol for this lethal disease with a high prevalence has not been approved yet. This study aimed to explore the efficacy of the main alkaloids of Isatis indigotica, one of the richest plant sources of alkaloids against SARS-CoV-2 targets computationally. Materials and Methods: 3D structures of the target proteins including 3CLpro; PLpro, and RdRp were downloaded from Protein Data Bank. The structures of ligands were retrieved from PubChem database or optimized by ORCA program. Ritonavir, Lopinavir, Sofosbuvir, and Remdesivir were selected as control inhibitors. Docking calculations were performed by AutoDock Vina option and top-ranked compounds were subjected to molecular dynamics simulation by Gromacs 5.1.4 simulation package. Result: The results showed that all 15 compounds had stronger interactions with PLpro in comparison to the other enzymes. Dihydroxylisopropylidenylisatisine A binds to the active site of PLpro with highest affinity (–9.3 kcal/mol) which is even more than the binding constants of Ritonavir and Lopinavir. Of the 15 compounds, Dihydroxylisopropylidenylisatisine A and Isatibisindosulfonic acid B had the highest tendency to bind to 3CLpro. Dihydroxylisopropylidenylisatisine A, Indirubin, Insatindibisindolamide A, Indigo, Insatindibisindolamide B, Isatibisindosulfonic acid B and Isatindosulfonic acid B had the highest RdRp binding affinity even more Remdesivir. Conclusion: Based on the results, the highest and weakest interaction with all three enzymes was observed for Dihydroxylisopropylidenylisatisine A and Epigoitrin, respectively. Based on these findings, Dihydroxylisopropylidenylsatistine A might be potential therapeutic candidate against SARS-CoV-2.
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来源期刊
Journal of Reports in Pharmaceutical Sciences
Journal of Reports in Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
1.40
自引率
0.00%
发文量
0
期刊介绍: The Journal of Reports in Pharmaceutical Sciences(JRPS) is a biannually peer-reviewed multi-disciplinary pharmaceutical publication to serve as a means for scientific information exchange in the international pharmaceutical forum. It accepts novel findings that contribute to advancement of scientific knowledge in pharmaceutical fields that not published or under consideration for publication anywhere else for publication in JRPS as original research article. all aspects of pharmaceutical sciences consist of medicinal chemistry, molecular modeling, drug design, pharmaceutics, biopharmacy, pharmaceutical nanotechnology, pharmacognosy, natural products, pharmaceutical biotechnology, pharmacology, toxicology and clinical pharmacy.
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