传统(悉达医学)多草药配方中植物成分的计算机抗病毒评估——靶向Mpro和泛冠状病毒融合后刺突蛋白

IF 3.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Sumit Kumar Mandal , MD Muzaffar-Ur Rehman , Ashish Katyal , Kanishk Rajvanshi , Manoj Kannan , Mohit Garg , Sankaranarayanan Murugesan , P.R. Deepa
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引用次数: 1

摘要

背景和目的SARS-CoV-2 病毒病原体的新颖性和治疗标准药物的缺乏,一直是抗击这种致命感染的主要挑战。天然产品提供了安全有效的治疗方法,而传统民族医药则可以提供这方面的线索。实验过程我们利用 Schrodinger 软件,将 32 种植物化学物质与病毒融合后 Spike 糖蛋白和 Mpro 进行对接,然后进行分子动力学分析。结果Kabasura Kudineer中植物化学物质的结合亲和力显示出以下前五位生物活性物质:槲皮素、木犀草素、5-羟基-7,8-二甲氧基黄酮、黄芩苷与 Mpro 靶标结合,没食子酸、胡椒龙葵碱、樱草酚、榄香酚、胡椒碱与融合后穗状病毒蛋白靶标结合。分子动力学模拟和 MM-PBSA 分析表明,槲皮素和没食子酸在与各自的病毒靶标复合物结合时表现出稳定性和良好的自由能变化。这些配体的硅学药代动力学分析表明,它们具有适当的药物相似性:(这些结果提供了:(a)本土释迦配方抗病毒疗效的潜在机制,其靶点是 Mpro 和融合后 Spike 蛋白(b)顶级生物活性先导分子,可开发为基于天然产品的抗病毒药物疗法,其多生物保护效应可用于控制与 COVID-19 相关的并发症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation – Targeting Mpro and pan-coronavirus post-fusion Spike protein

In silico anti-viral assessment of phytoconstituents in a traditional (Siddha Medicine) polyherbal formulation – Targeting Mpro and pan-coronavirus post-fusion Spike protein

Background and aim

Novel nature of the viral pathogen SARS-CoV-2 and the absence of standard drugs for treatment, have been a major challenge to combat this deadly infection. Natural products offer safe and effective remedy, for which traditional ethnic medicine can provide leads. An indigenous poly-herbal formulation, Kabasura Kudineer from Siddha system of medicine was evaluated here using a combination of computational approaches, to identify potential inhibitors against two anti-SARS-CoV-2 targets – post-fusion Spike protein (structural protein) and main protease (Mpro, non-structural protein).

Experimental procedure

We docked 32 phytochemicals from the poly-herbal formulation against viral post-fusion Spike glycoprotein and Mpro followed by molecular dynamics using Schrodinger software. Drug-likeness analysis was performed using machine learning (ML) approach and pkCSM.

Results

The binding affinity of the phytochemicals in Kabasura Kudineer revealed the following top-five bioactives: Quercetin > Luteolin > Chrysoeriol > 5-Hydroxy-7,8-Dimethoxyflavone > Scutellarein against Mpro target, and Gallic acid > Piperlonguminine > Chrysoeriol > Elemol > Piperine against post-fusion Spike protein target. Quercetin and Gallic acid exhibited binding stability in complexation with their respective viral-targets and favourable free energy change as revealed by the molecular dynamics simulations and MM-PBSA analysis. In silico predicted pharmacokinetic profiling of these ligands revealed appropriate drug-likeness properties.

Conclusion

These outcomes provide: (a) potential mechanism for the anti-viral efficacy of the indigenous Siddha formulation, targeting Mpro and post-fusion Spike protein (b) top bioactive lead-molecules that may be developed as natural product-based anti-viral pharmacotherapy and their pleiotropic protective effects may be leveraged to manage co-morbidities associated with COVID-19.

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来源期刊
Journal of Traditional and Complementary Medicine
Journal of Traditional and Complementary Medicine Medicine-Complementary and Alternative Medicine
CiteScore
9.30
自引率
6.70%
发文量
78
审稿时长
66 days
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