Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, India.
School of Pharmacy, University of East Anglia, Norwich, UK.
J Biomol Struct Dyn. 2022 Aug;40(12):5295-5308. doi: 10.1080/07391102.2020.1869588. Epub 2021 Jan 18.
Traditionally, is widely used as an immune booster, anti-viral, and for multiple medicinal purposes. The present study investigated the withanolides as an immune booster and anti-viral agents against the coronavirus-19. Withanolides from were retrieved from the open-source database, their targets were predicted using DIGEP-Pred, and the protein-protein interaction was evaluated. The drug-likeness score and intestinal absorptivity of each compound were also predicted. The network of compounds, proteins, and modulated pathways was constructed using Cytoscape, and docking was performed using autodock4.0, and selected protein-ligand complexes were subjected to 100 ns Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Withanolide_Q was predicted to modulate the highest number of proteins, showed human intestinal absorption, and was predicted for the highest drug-likeness score. Similarly, combined network interaction identified Withanolide_Q to target the highest number of proteins; RAC1 was majorly targeted, and fluid shear stress and atherosclerosis associated pathway were chiefly regulated. Similarly, Withanolide_D and Withanolide_G were predicted to have a better binding affinity with PLpro, Withanolide_M with 3CLpro, and Withanolide_M with spike protein based on binding energy and number of hydrogen bond interactions. MD studies suggested Withanoside_I with the highest binding free energy (ΔG-31.56 kcal/mol) as the most promising inhibitor. Among multiple withanolides from Withanolide_D, Withanolide_G, Withanolide_M, and Withanolide_Q were predicted as the lead hits based on drug-likeness score, modulated proteins, and docking score to boost the immune system and inhibit the COVID-19 infection, which could primarily act against COVID-19. HighlightsWithanolides are immunity boosters.Withanolides are a group of bio-actives with potential anti-viral properties.Withanolide_G, Withanolide_I, and Withanolide_M from showed the highest binding affinity with PLpro, 3CLpro, and spike protein, respectively.Withanolides from holds promising anti-viral efficacy against COVID-19.Communicated by Vsevolod Makeev.
传统上，被广泛用作免疫增强剂、抗病毒剂和多种药用目的。本研究调查了作为免疫增强剂和抗病毒剂的醉茄内酯类化合物，以对抗冠状病毒-19。从开放源数据库中检索了 中的醉茄内酯类化合物，使用 DIGEP-Pred 预测其靶标，并评估蛋白质-蛋白质相互作用。还预测了每个化合物的药物相似性评分和肠道吸收率。使用 Cytoscape 构建化合物、蛋白质和调节途径的网络图，并使用 autodock4.0 进行对接，选择蛋白配体复合物进行 100ns 分子动力学模拟。使用 MM-GBSA 方法对分子动力学轨迹进行自由能计算。预测醉茄内酯_Q 可以调节最多数量的蛋白质，表现出人类肠道吸收，并且预测具有最高的药物相似性评分。同样，联合网络相互作用表明醉茄内酯_Q 靶向最多数量的蛋白质；RAC1 是主要靶点，流体剪切应激和动脉粥样硬化相关途径主要受到调节。同样，预测醉茄内酯_D 和醉茄内酯_G 与 PLpro 的结合亲和力更好，醉茄内酯_M 与 3CLpro 的结合亲和力更好，醉茄内酯_M 与刺突蛋白的结合亲和力更好，基于结合能和氢键相互作用的数量。MD 研究表明，结合能最高的 Withanoside_I（-31.56kcal/mol）是最有前途的抑制剂。在 中的多种醉茄内酯类化合物中，基于药物相似性评分、调节蛋白和对接评分，醉茄内酯_D、醉茄内酯_G、醉茄内酯_M 和醉茄内酯_Q 被预测为先导化合物，以增强免疫系统并抑制 COVID-19 感染，这可能主要针对 COVID-19。亮点醉茄内酯类化合物是免疫增强剂。醉茄内酯类化合物是一组具有潜在抗病毒特性的生物活性物质。醉茄内酯_G、醉茄内酯_I 和醉茄内酯_M 与 PLpro、3CLpro 和刺突蛋白的结合亲和力最高。来自 的醉茄内酯类化合物对 COVID-19 具有潜在的抗病毒疗效。由 Vsevolod Makeev 传达。
