Discovery of novel Trichoderma-based bioactive compounds for controlling potato virus Y based on molecular docking and molecular dynamics simulation techniques

IF 5.2 2区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY

Chemical and Biological Technologies in Agriculture Pub Date : 2024-08-08 DOI:10.1186/s40538-024-00629-2

Mohamed N. Rizk, Hammad A. Ketta, Yasser M. Shabana

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Abstract

Background

Although potato virus Y (PVY) is the most serious virus-infecting potato plants worldwide, the losses concurred by it remain unmanageable due to the lack of efficient anti-PVY agents. Hence, the objective of this study was to assess the antiviral properties of secondary metabolite compounds obtained from culture filtrates of four Trichoderma spp. isolates. The assessment was conducted using computational methods, including molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, as well as molecular dynamics simulations. The aim was to develop novel and effective agents for combating PVY.

Results

The GC–MS analysis of the studied Trichoderma spp. secondary metabolites revealed 24 compounds with relative amounts exceeding 10%. Molecular docking was then performed using MOE software to evaluate the activity of these compounds against the PVY protein coat (PDB-ID: 6HXX). Ningnanmycin and ribavirin, known plant virus inhibitors, were employed as reference ligands for comparison. Among the compounds tested, C9, C10, C13, and C19 exhibited superior docking scores, root mean square deviation (RMSD) values, and binding modes compared to the reference ligands. In addition, these compounds successfully passed the ADMET analysis. Further investigation focused on compounds C13 and C19, which underwent in-depth analysis through MDs for 100 ns. The MDs trajectories demonstrated that both complexes exhibited favorable stability, compactness, and binding modes throughout the simulation period. However, the C19/PVY-CP complex outperformed the C13 complex in all calculated parameters such as RMSD, root mean square fluctuation (RMSF), radius of gyration (RoG), solvent-accessible surface area (SASA), and intermolecular hydrogen bonds. Interestingly, these findings aligned with the results obtained from the docking analysis, indicating that C9 and C10 possess high potential against PVY, as they exhibited binding modes like that of C19.

Conclusion

These promising outcomes provide a solid foundation for considering the potential use of compounds C9, C10, C13, and C19 as antiviral agents. Further experimental validation and in-depth studies are warranted to assess the efficacy and safety of these compounds and their potential as antiviral therapeutics. To our knowledge, this is the first report to study the biological activities of the Trichoderma-based bioactive compounds against PVY using computational techniques.

Graphical abstract

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基于分子对接和分子动力学模拟技术发现控制马铃薯病毒 Y 的新型毛霉生物活性化合物

背景虽然马铃薯病毒 Y（PVY）是全球马铃薯植物感染最严重的病毒，但由于缺乏有效的抗 PVY 制剂，其造成的损失仍然难以控制。因此，本研究旨在评估从四种毛霉属分离物的培养滤液中获得的次生代谢物化合物的抗病毒特性。评估采用计算方法进行，包括分子对接、吸收、分布、代谢、排泄和毒性（ADMET）分析以及分子动力学模拟。结果对所研究的毛霉属次生代谢物进行气相色谱-质谱分析，发现 24 种化合物的相对含量超过 10%。然后使用 MOE 软件进行了分子对接，以评估这些化合物对 PVY 蛋白衣壳（PDB-ID：6HXX）的活性。宁南霉素和利巴韦林是已知的植物病毒抑制剂，被用作参考配体进行比较。在测试的化合物中，C9、C10、C13 和 C19 的对接得分、均方根偏差（RMSD）值和结合模式均优于参考配体。此外，这些化合物还成功通过了 ADMET 分析。进一步研究的重点是 C13 和 C19 化合物，这两个化合物通过 100 ns 的 MD 进行了深入分析。MDs 轨迹表明，这两种复合物在整个模拟期间都表现出良好的稳定性、紧凑性和结合模式。然而，C19/PVY-CP 复合物在 RMSD、均方根波动（RMSF）、回旋半径（RoG）、可溶解表面积（SASA）和分子间氢键等所有计算参数上都优于 C13 复合物。有趣的是，这些发现与对接分析的结果一致，表明 C9 和 C10 具有很高的抗 PVY 的潜力，因为它们表现出与 C19 相似的结合模式。需要进一步的实验验证和深入研究，以评估这些化合物的有效性和安全性及其作为抗病毒疗法的潜力。据我们所知，这是第一份利用计算技术研究基于毛霉的生物活性化合物对 PVY 的生物活性的报告。

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

Chemical and Biological Technologies in Agriculture Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

6.80

自引率

3.00%

发文量

审稿时长

15 weeks

期刊介绍： Chemical and Biological Technologies in Agriculture is an international, interdisciplinary, peer-reviewed forum for the advancement and application to all fields of agriculture of modern chemical, biochemical and molecular technologies. The scope of this journal includes chemical and biochemical processes aimed to increase sustainable agricultural and food production, the evaluation of quality and origin of raw primary products and their transformation into foods and chemicals, as well as environmental monitoring and remediation. Of special interest are the effects of chemical and biochemical technologies, also at the nano and supramolecular scale, on the relationships between soil, plants, microorganisms and their environment, with the help of modern bioinformatics. Another special focus is the use of modern bioorganic and biological chemistry to develop new technologies for plant nutrition and bio-stimulation, advancement of biorefineries from biomasses, safe and traceable food products, carbon storage in soil and plants and restoration of contaminated soils to agriculture. This journal presents the first opportunity to bring together researchers from a wide number of disciplines within the agricultural chemical and biological sciences, from both industry and academia. The principle aim of Chemical and Biological Technologies in Agriculture is to allow the exchange of the most advanced chemical and biochemical knowledge to develop technologies which address one of the most pressing challenges of our times - sustaining a growing world population. Chemical and Biological Technologies in Agriculture publishes original research articles, short letters and invited reviews. Articles from scientists in industry, academia as well as private research institutes, non-governmental and environmental organizations are encouraged.