Wang Bin, Ding Yan, Zhao Penghui, Li Wei, Li Ming, Zhu Jingbo, Ye Shuhong
School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning, 116034, China.
School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning, 116034, China.
Comput Biol Med. 2022 Apr;143:105241. doi: 10.1016/j.compbiomed.2022.105241. Epub 2022 Jan 26.
Recently, the value of natural products has been extensively considered because these resources can potentially be applied to prevent and treat coronavirus pneumonia 2019 (COVID-19). However, the discovery of nature drugs is problematic because of their complex composition and active mechanisms.
This comprehensive study was performed on flavonoids, which are compounds with anti-inflammatory and antiviral effects, to show drug discovery and active mechanism from natural products in the treatment of COVID-19 via a systems pharmacological model. First, a chemical library of 255 potential flavonoids was constructed. Second, the pharmacodynamic basis and mechanism of action between flavonoids and COVID-19 were explored by constructing a compound-target and target-disease network, targets protein-protein interaction (PPI), MCODE analysis, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment.
In total, 105 active flavonoid components were identified, of which 6 were major candidate compounds (quercetin, epigallocatechin-3-gallate (EGCG), luteolin, fisetin, wogonin, and licochalcone A). 152 associated targets were yielded based on network construction, and 7 family proteins (PTGS, GSK3β, ABC, NOS, EGFR, and IL) were included as central hub targets. Moreover, 528 GO items and 178 KEGG pathways were selected through enrichment of target functions. Lastly, molecular docking demonstrated good stability of the combination of selected flavonoids with 3CL Pro and ACEⅡ.
Natural flavonoids could enable resistance against COVID-19 by regulating inflammatory, antiviral, and immune responses, and repairing tissue injury. This study has scientific significance for the selective utilization of natural products, medicinal value enhancement of flavonoids, and drug screening for the treatment of COVID-19 induced by SARS-COV-2.
近年来，天然产物的价值受到广泛关注，因为这些资源有望用于预防和治疗2019冠状病毒病（COVID-19）。然而，由于天然药物成分复杂、作用机制多样，其发现过程存在一定问题。
本综合研究以具有抗炎和抗病毒作用的黄酮类化合物为研究对象，通过系统药理学模型展示从天然产物中发现治疗COVID-19的药物及其作用机制。首先，构建了包含255种潜在黄酮类化合物的化学文库。其次，通过构建化合物-靶点、靶点-疾病网络、靶点蛋白质-蛋白质相互作用（PPI）、MCODE分析、基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集，探索黄酮类化合物与COVID-19之间的药效学基础和作用机制。
共鉴定出105种活性黄酮类成分，其中6种为主要候选化合物（槲皮素、表没食子儿没食子酸酯（EGCG）、木犀草素、非瑟酮、汉黄芩素和甘草查尔酮A）。基于网络构建得到152个相关靶点，其中7种家族蛋白（PTGS、GSK3β、ABC、NOS、EGFR和IL）被确定为核心枢纽靶点。此外，通过靶点功能富集筛选出528个GO条目和178条KEGG通路。最后，分子对接结果表明所选黄酮类化合物与3CL Pro和ACEⅡ的结合具有良好的稳定性。
天然黄酮类化合物可通过调节炎症、抗病毒和免疫反应以及修复组织损伤来抵抗COVID-19。本研究对于天然产物的选择性利用、黄酮类化合物药用价值的提升以及SARS-CoV-2所致COVID-19治疗药物的筛选具有科学意义。
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