Abstract

Traditionally, Withania somnifera 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 Withania somnifera 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_bind-31.56 kcal/mol) as the most promising inhibitor. Among multiple withanolides from W. somnifera, 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.

• Highlights

• Withanolides are immunity boosters.

• Withanolides are a group of bio-actives with potential anti-viral properties.

• Withanolide_G, Withanolide_I, and Withanolide_M from Withania somnifera showed the highest binding affinity with PLpro, 3CLpro, and spike protein, respectively.

• Withanolides from Withania somnifera holds promising anti-viral efficacy against COVID-19.

Communicated by Vsevolod Makeev

摘要

传统上，睡茄被广泛用作免疫增强剂、抗病毒剂和多种药用用途。本研究调查了 withanolides 作为免疫增强剂和抗冠状病毒 19 的抗病毒剂。来自Withania somnifera的 Withanolides从开源数据库中检索到它们的目标，使用 DIGEP-Pred 预测它们的目标，并评估蛋白质-蛋白质相互作用。还预测了每种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、蛋白质和调节通路的网络，使用 autodock4.0 进行对接，并对选定的蛋白质-配体复合物进行 100 ns 分子动力学模拟。通过MM-GBSA方法对分子动力学轨迹进行自由能计算。预计 Withanolide_Q 可调节最多数量的蛋白质，显示人体肠道吸收，并预测最高的药物相似性评分。类似地，联合网络相互作用确定了 Withanolide_Q 以最多的蛋白质为目标；RAC1主要被靶向，主要调节流体剪切应力和动脉粥样硬化相关通路。类似地，根据结合能和氢键相互作用的数量，预计 Withanolide_D 和 Withanolide_G 与 PLpro、Withanolide_M 与 3CLpro 以及 Withanolide_M 与尖峰蛋白具有更好的结合亲和力。MD 研究表明 Withanoside_I 具有最高的结合自由能 (ΔG_结合-31.56 kcal/mol）作为最有希望的抑制剂。在来自W. somnifera 的多种 withanolide 中， Withanolide_D、Withanolide_G、Withanolide_M 和 Withanolide_Q 被预测为基于药物相似性评分、调节蛋白和对接评分的领先药物，以增强免疫系统并抑制 COVID-19 感染，这可能主要针对 COVID-19。

• 强调

• Withanolides 是免疫增强剂。

• Withanolides 是一组具有潜在抗病毒特性的生物活性物质。

• 来自Withania somnifera的Withanolide_G、Withanolide_I 和 Withanolide_M 分别显示出与 PLpro、3CLpro 和尖峰蛋白的最高结合亲和力。

• 来自Withania somnifera的 Withanolides 对 COVID-19 具有良好的抗病毒功效。

由 Vsevolod Makeev 通讯