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首页> 《中国测试》期刊 >本期导读>傣药方在治疗新型冠状病毒肺炎中作用的网络药理学和分子对接分析

傣药方在治疗新型冠状病毒肺炎中作用的网络药理学和分子对接分析

175    2021-09-23

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作者:王晨钰1,2, 韩涵3, 郭磊2, 刘同祥1, 唐丽1

作者单位:1. 民族医药教育部重点实验室(中央民族大学),中央民族大学药学院,北京 100081;
2. 军事科学院军事医学研究院毒物药物研究所 抗毒药物与毒理学国家重点实验室,北京 100850;
3. 中国人民解放军总医院京中医疗区礼士路门诊部,北京 100045


关键词:网络药理学;分子对接;傣药;新型冠状病毒肺炎(COVID-19);SARS-CoV-2 3CL水解酶;ACE2


摘要:

采用网络药理学和分子对接技术分析源自“瘴疠之区”丰富认识的傣医药在治疗新型冠状病毒肺炎(COVID-19)中所发挥的作用。基于文献调研,确定傣医药对 COVID-19治疗方案中三种傣药方的化学成分;采用中药系统药理分析平台、中药化学成分数据库和Swiss target prediction数据库对每个药方中主要化学成分的潜在靶点进行整理;在基因挖掘软件(GenCLiP3)和GeneCard数据库搜索COVID-19相关靶点,绘制中药调控网络图;使用STRING数据库构建靶点蛋白质蛋白质相互作用(PPI)网络;同时进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,并对关键化学成分与靶蛋白严重急性呼吸综合征冠状病毒2(SARS-CoV-2)3CL水解酶和血管紧张素转化酶2(ACE2)进行分子对接。研究结果表明,傣药方所含化合物以黄酮类、萜类等为主,主要活性成分β-谷甾醇、槲皮素、儿茶素等可作用于周期蛋白依赖性激酶2(CDK2)、丝裂原活化蛋白激酶1(MAPK1)等多个靶点,调节MAPK信号通路、白介素-17(IL-17)信号通路、酪氨酸激酶-转录因子(JAK-STAT)信号通路、核转录因子(NF)-κB信号通路、花生四烯酸代谢通路等多条通路。药方1核心靶点包括MAPK1、JAK1等,以抗炎、病毒感染细胞的通路为主,以提高机体免疫能力;药方2核心靶点则包括环加氧酶1(PTGS1)、一氧化氮合酶2(NOS2)等,集中于病原菌、病毒感染通路、抗炎信号通路等,对临床上所出现的发热不退等症状可协同调控;药方3核心靶点包括磷脂酰肌醇-3-激酶催化亚基α(PIK3CA)、IL-6等,以炎症信号通路、细胞的增殖凋亡通路为主,对抗更为严重的临床症状。靶点、通路的差异可作为这三种药方对COVID-19分别对症下药的初步理论依据。


Network pharmacology and molecular docking analysis on the role of Dai prescriptions in the treatment of new coronavirus pneumonia
WANG Chenyu1,2, HAN Han3, GUO Lei2, LIU Tongxiang1, TANG Li1
1. Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, School of Pharmacy, Minzu University of China, Beijing 100081, China;
2. State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Toxicology and Pharmacology, Academy of Military Medical Sciences, Beijing 100850, China;
3. Lishilu Clinic, Central Beijing Branch, PLA General Hospital, Beijing 100045, China
Abstract: To use network pharmacology and molecular docking technique to analyze the role of Dai medicine, which has rich knowledge originated from the “Miasma Zone”, in the treatment of new coronavirus pneumonia (COVID-19). The chemical components of the three Dai prescriptions in Dai medicine’s treatment plan for COVID-19 were determined on the literature research. The potential targets of the main components in each prescription were discovered using the systematic pharmacological analysis platform on Chinese medicine, the database of Chinese medicine chemical component and the Swiss target prediction database. The Chinese medicine regulatory network were depicted after searching COVID-19 related targets in Gene Cluster Literature Profiles (GenCLiP3) and GeneCard databases. The target protein protein interaction (PPI) network was built by using STRING database. The gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed at the same time. The molecular docking were finally made for key component and target proteins (SARS-CoV-2 3CL hydrolase and ACE2). The compounds contained in the Dai prescriptions are mainly flavonoids, terpenes, etc. The main active ingredients such as β-sitosterol, quercetin and catechin can act on multiple targets like cyclin-dependent kinases 2 (CDK2), mitogen-activated protein kinase 1(MAPK1), and regulate multiple signal pathways such as MAPK, interleukin-17(IL-17), janus activated kinase-signal transducer and activator of transcriptions (JAK-STAT), nuclear transcription factor (NF)-κB, arachidonic acid metabolism pathway etc. The core targets of prescription 1 are MAPK1, JAK1, etc., which are based on the pathways of anti-inflammatory and virus-infected cells to improve the body's immunity. The core targets of prescription 2 are prostaglandin-endoperoxide synthase 1(PTGS1), nitric oxide synthase 2 (NOS2) etc., focusing on pathogenic bacteria, viral infection pathways, and anti-inflammatory signaling pathways, which can coordinately regulate the symptoms of fever and others appear in the clinic. The core targets of prescription 3 are phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), IL-6 etc., and the corresponding clinical symptoms are more serious, which are contributed by main inflammation-related signal pathways, and cell proliferation and apoptosis pathways. The differences in targets and pathways can be used as a preliminary theoretical basis for the three Dai prescriptions for treatment of COVID-19 towards different symptoms.
Keywords: network pharmacology;molecular docking;Dai medicine;novel coronavirus pneumonia (COVID-19);SARS-CoV-2 3CL hydrolase;ACE2
2021, 47(9):70-81  收稿日期: 2021-01-29;收到修改稿日期: 2021-03-09
基金项目: 国家自然科学基金项目(81873397);河北省自然科学基金项目(B2019209330)
作者简介: 王晨钰(1998-),女,河南南阳市人,硕士研究生,专业方向为药物分析学
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