Soybean-associated endophytic fungi as potential source for anti-COVID-19 metabolites supported by docking analysis
Soybean-associated endophytic fungi as potential source for anti-COVID-19 metabolites supported by docking analysis
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DOI：
10.1111/jam.15031
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发表时间：
2021-03-09
影响因子：
4
通讯作者：
Abdelmohsen, U. R.
中科院分区：
文献类型：
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作者：
El-Hawary, S. S.;Mohammed, R.;Abdelmohsen, U. R.
目的鉴定内生真菌土曲霉（Aspergillus terreus）产生的代谢产物，并通过计算机模拟研究所鉴定的代谢产物对新型冠状病毒COVID-19的抗病毒活性。terreus，与大豆根相关的内生真菌，然后使用OSMAC方法在五种不同的培养基中传代培养。采用液相色谱-高分辨率质谱（LC-HRMS）对介质乙酸乙酯浸提液进行分析。此外，使用MetaboAnalyst 4.0对获得的LC-MS数据进行统计学处理。针对COVID-19主要蛋白酶（M-pro）对去复制代谢物进行分子对接研究。代谢组学分析显示存在18种属于不同化学类别的化合物。醌类、聚酮类和异香豆素类是含量最丰富的种类。多因素分析表明，马铃薯葡萄糖肉汤和改良马铃薯葡萄糖肉汤是最佳的代谢产物产生的培养基。分子对接研究表明，代谢产物阿吉利特B1和3a-羟基-3，5-二氢莫纳可林L对COVID-19主要蛋白酶（M-pro）的结合能评分最高。（-9中心点473）和（-9中心点386），它们与催化二联体强烈相互作用结论代谢组学和计算机模拟方法的结合使得寻找抗COVID-19抗体的途径更短。19天然产品在较短的时间。在分子对接研究中，发现去复制代谢产物曲霉素B1和3 α-羟基-3，5-二氢莫纳可林L是有效的抗COVID-19候选药物。土可以被认为是天然生物活性产品的潜在来源。此外，开发代谢产物曲霉素B1和3 α-羟基-3，5-二氢莫纳可林L作为植物药物用于管理COVID-19的可能性。
Aims To identify the metabolites produced by the endophytic fungus, Aspergillus terreus and to explore the anti-viral activity of the identified metabolites against the pandemic disease COVID-19 in-silico.Methods and Results Herein, we reported the isolation of A. terreus, the endophytic fungus associated with soybean roots, which is then subcultured using OSMAC approach in five different culture media. Analytical analysis of media ethylacetate extracts using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) was carried out. Furthermore, the obtained LC-MS data were statistically processed with MetaboAnalyst 4.0. Molecular docking studies were performed for the dereplicated metabolites against COVID-19 main protease (M-pro). Metabolomic profiling revealed the presence of 18 compounds belonging to different chemical classes. Quinones, polyketides and isocoumarins were the most abundant classes. Multivariate analysis revealed that potato dextrose broth and modified potato dextrose broth are the optimal media for metabolites production. Molecular docking studies declared that the metabolites, Aspergillide B1 and 3a-Hydroxy-3, 5-dihydromonacolin L showed the highest binding energy scores towards COVID-19 main protease (M-pro) (-9 center dot 473) and (-9 center dot 386), respectively, and they interact strongly with the catalytic dyad (His41 and Cys145) amino acid residues of M-pro.Conclusions A combination of metabolomics and in-silico approaches have allowed a shorter route to search for anti-COVID-19 natural products in a shorter time. The dereplicated metabolites, aspergillide B1 and 3 alpha-Hydroxy-3, 5-dihydromonacolin L were found to be potent anti-COVID-19 drug candidates in the molecular docking study.Significance and Impact of the Study This study revealed that the endophytic fungus, A. terreus can be considered as a potential source of natural bioactive products. In addition to, the possibility of developing the metabolites, aspergillide B1 and 3 alpha-Hydroxy-3, 5-dihydromonacolin L to be used as phytopharmaceuticals for the management of COVID-19.