鱼腥草治疗病毒性肺炎作用机制的“成分-靶点-通路”多层次互作网络研究

目的 基于网络药理学方法分析鱼腥草Houttuynia cordata治疗病毒性肺炎的分子生物学机制，并对其防治新型冠状病毒肺炎（COVID-19）的可行性进行评估。方法 采用在线数据库TCMSP、PubChem Search、Swiss target prediction、Genecards、OMIM获得鱼腥草活性成分、成分靶点及疾病靶点信息。借助Cytoscape3.7.1软件构建鱼腥草活性成分-病毒性肺炎作用靶标网络，将靶蛋白运用String10.0数据库进行蛋白质相互作用（PPI）网络分析，通过DAVID 6.8数据库进行基因本体论（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析，预测其作用机制。结果 从鱼腥草中共筛选出16个主要活性成分，共涉及到311个靶点，与病毒性肺炎相关的靶点64个。从PPI网络分析中发现关键靶点为IL2、TNF、AKT1、JUN、VEGFA、MAPK8、CXCL8、PTGS2等。GO和KEGG通路富集分析发现，鱼腥草治疗病毒性肺炎可能与细胞因子受体结合、细胞因子活性、受体配体活性、磷酸酶结合、蛋白磷酸酶结合、内肽酶活性、生长因子受体结合、肿瘤坏死因子受体超家族结合、丝氨酸型内肽酶活性等73个GO功能有关，涉及到TNF信号通路、IL-17信号通路、C型凝集素受体信号通路、卡波西氏肉瘤相关疱疹病毒感染、甲型流感、Toll样受体信号通路、T细胞受体信号通路、人巨细胞病毒感染、NOD样受体信号通路等130个信号通路。结论 鱼腥草针对病毒性肺炎具有多成分、多靶点、多机制的显著治疗作用，并且推测能够通过调节与抗炎、抗病毒、免疫调节有关的生物通路对COVID-19进行防御和治疗。

Study on component-target-pathway multiple interactive network to reveal mechanism of Houttuynia cordata in treatment of viral pneumonia

Objective To analyze the molecular biological mechanism of Houttuynia cordata in treatment of viral pneumonia based on network pharmacology, and to evaluate its feasibility in prevention and treatment of Corona Virus Disease 2019 (COVID-19). Methods Online databases TCMSP, PubChem Search, Swiss Target Prediction, Genecards and OMIM were used to obtain the information of active components, component targets and disease targets of H. cordata. Cytoscape 3.7.1 software was used to construct the H. cordata activity-viral pneumonia target network, and the target protein was used to carry out protein-protein interaction (PPI) network using String10.0 database. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed using DAVID 6.8 database to predict the mechanism of action. Results A total of 16 main active components were screened from H. cordata, involving 311 targets, 64 targets related to viral pneumonia. The key targets of PPI network analysis were IL2, TNF, AKT1, JUN, VEGFA, MAPK8, CXCL8, PTGS2, etc. GO and KEGG pathway enrichment analysis found that its treatment of viral pneumonia may combine with cytokines receptors, cytokine activity, receptor ligands activity, as well as the combination of phosphatase, inside the protein phosphatase, peptide enzyme activity, growth factor receptor, tumor necrosis factor receptor superfamily combination, serine peptidase activity within about 73 function, 130 signaling pathways including TNF signaling pathway, IL-17 signaling pathway, C-type lectin receptor signaling pathway, Kapoussi''s sarcoma associated herpes virus infection, influenza A, Toll-like receptor signaling pathway, T cell receptor signaling pathway, human cytomegalovirus infection, nod-like receptor signaling pathway were involved. Conclusion H. cordata for viral pneumonia has multiple components, multiple targets, multiple mechanisms of significant therapeutic effect, and speculated that can adjust the related to anti-inflammation, antivirus, immunomodulatory biological pathways of COVID-19 prevention and treatment.