Essential oil constituents of regional ethnomedicinal plants as potential inhibitors of SARS-CoV-2 Mpro: an integrated molecular docking, molecular dynamics and QM/MM study.

IF 2.7 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ambalika Phonglo, Dikshita Dowerah, Srutishree Sarma, Najima Ahmed, Priyanka Dutta, Moumita Basumutary, Ramesh Ch Deka
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引用次数: 0

Abstract

The scientific community has achieved a remarkable milestone by creating efficacious vaccines against the SARS-CoV-2 virus. The treatment alternatives are still restricted, though. The bioactive ingredients present in natural plants are known to exhibit diverse pharmacological effects against many diseases. Using computational techniques such as molecular docking, drug-likeness, ADMET study, MD simulation, and our own N-layered Integrated molecular Orbital and Molecular mechanics (ONIOM) calculations, this study aimed to investigate essential oil constituents of Lindera neesiana, Litsea cubeba and Zanthoxylum armatum DC plants as a potential natural inhibitor of SARS-CoV-2 main protease (Mpro). To determine their binding affinity, 107 phytochemical substances in total were docked inside the binding pocket of Mpro. Copaene showed the highest binding affinity among the 107 compounds, with an energy of -7.90 kcal/mol. Furthermore, physiochemical and ADMET properties were evaluated for the top five phytocompounds. The studied phytocompounds showed good physiochemical and pharmacokinetic behaviour with no associated toxicity. MD simulation further provided evidence for stable interaction of phytocompounds within the binding pocket of Mpro. Subsequently, ONIOM calculation was done on the best-hit complex, wherein the hydrogen bonding interactions were retained with appreciable negative energy. These in silico results indicate that the specific phytocompounds present in essential oils of L. neesiana, L. cubeba, and Z. armatum DC have significant inhibitor ability against SARS-CoV-2 main protease and could be explored for future therapeutic investigations.

区域民族药植物精油成分作为SARS-CoV-2 Mpro潜在抑制剂:综合分子对接、分子动力学和QM/MM研究
科学界通过研制出有效的SARS-CoV-2病毒疫苗,取得了一个非凡的里程碑。不过,治疗方法仍然有限。已知天然植物中存在的生物活性成分对许多疾病表现出不同的药理作用。本研究采用分子对接、药物相似性、ADMET研究、MD模拟等计算技术,结合自己的n层集成分子轨道和分子力学(ONIOM)计算,旨在研究林荫、山核桃和花椒DC植物精油成分作为潜在的天然抑制剂的作用。为了确定它们的结合亲和力,共将107种植物化学物质停靠在Mpro的结合口袋中。在107种化合物中,Copaene的结合能最高,为-7.90 kcal/mol。此外,对前5种植物化合物的理化和ADMET性质进行了评价。所研究的植物化合物表现出良好的物理化学和药代动力学行为,无相关毒性。MD模拟进一步提供了Mpro结合口袋内植物化合物稳定相互作用的证据。随后,对最受打击的配合物进行了onionm计算,其中氢键相互作用以可观的负能量保留。这些实验结果表明,在neesiana、L. cubeba和Z. armatum DC精油中存在的特定植物化合物对SARS-CoV-2主要蛋白酶具有显著的抑制能力,可以在未来的治疗研究中进行探索。
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
Journal of Biomolecular Structure & Dynamics
Journal of Biomolecular Structure & Dynamics 生物-生化与分子生物学
CiteScore
8.90
自引率
9.10%
发文量
597
审稿时长
2 months
期刊介绍: The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.
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