目的 探寻醒脑静注射液（XNJI）保护新型冠状病毒（SARS-CoV-2）致神经系统损害的活性成分、靶点及通路，以期阐述其作用机制。方法 利用TCMSP、BATMAN、Swiss Target Prediction等数据库检索醒脑静注射液的中药的化学成分和作用靶点，使用Cytoscape软件分别构建醒脑静注射液“中药-活性成分-相关靶点”功效作用网络，通过GO富集和KEGG通路注释分析预测潜在的作用机制，并将醒脑静注射液中核心成分与SARS-CoV-2 3CL Mpro、血管紧张素转化酶II（ACE2）、2019-nCoV RBD/ACE2-B0AT1 complex进行分子对接验证。结果 筛选出醒脑静注射液105个活性成分，928个药物靶点，741个冠状病毒靶点，611个神经保护靶点，得到药物-疾病共同靶点83个，核心成分12个，关键靶点7个。GO富集分析共得到204个条目，KEGG注释分析共得到120条信号通路，涉及乙型肝炎通路、致癌通路、TNF、HIF-1及VEGF信号通路等。分子对接结果显示醒脑静注射液核心成分与3CL Mpro、ACE2、和complex的结合活性较好，其中绿莲皂苷元、山柰酚与3个蛋白的结合能均最低。结论 醒脑静注射液中核心成分绿莲皂苷元、山柰酚、5-羟基-6，7，3'，4'，5'-五甲氧基黄酮、异山柰素、桑黄素、栀子黄素A、槲皮素、艾黄素、染料木素、龙脑香内酯、姜黄素、榄香素等可能通过作用PARP1、PTGS2、MMP9、CDK2、ADORA2A、ALOX5、GSK3B等关键靶点，干预多种信号通路，调控炎症反应、细胞凋亡、氧化应激、血管生成等过程改善SARS-CoV-2对神经系统的损害，还可能与3CL Mpro、ACE2和complex结合以抑制病毒复制及对宿主细胞的感染，提示醒脑静注射液可能对SARS-CoV-2引发的神经系统损害具有积极的治疗作用。

Objective To explore the active compounds, targets and signaling pathways of Xingnaojing Injection (XNJI) for the treatment of neurological damage caused by SARS-CoV-2, so as to explore its mechanism. Methods Using TCMSP, BATMAN, Swiss Target Prediction, and other databases, the chemical compounds and targets of XNJI were retrieved. Cytoscape software was used to construct XNJI efficacy network of "drug-compounds-targets" for coronavirus and neuroprotection, and the action mechanism was predicted by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then core compounds were verified by molecular docking with 3CL Mpro, ACE2, and 2019-nCoV RBD/ACE2-B0AT1 complex. Results A total of 105 active compounds of XNJI, 928 drug targets, 741 targets of coronavirus, 611 targets of neuroprotection, 83 drug-disease common targets, 12 core compounds, and seven key targets were obtained. The function enrichment analysis of GO yielded 204 entries, KEGG pathway enrichment screened 120 signaling pathways, which included Hepatitis B, pathways in cancer, TNF, HIF-1, and VEGF signaling pathway, and so on. The results of molecular docking showed that core compounds of XNJI had a good bonding activity with 3CL Mpro, ACE2 and complex. The chlorogenin and kaempferol had the lowest binding energy with three proteins and might play an important role in treatment. Conclusion The core compounds in XNJI including chlorogenin, kaempferol, 5-hydroxy- 6,7,3',4',5'-pentamethoxyflavone, 3-methylkempferol, morin, gardenin, quercetin, artemisetin, genistein, dryobalanone, curcumin, and elemicin, which might interfere with various signaling pathways by acting on key targets like PARP1, PTGS2, MMP9, CDK2, ADORA2A, ALOX5, GSK3B, and regulate the inflammatory response, apoptosis, oxidative stress, angiogenesis, and other processes to improve the neurological damage caused by SARS-CoV-2, and inhibit virus replication and prevent infection of the host cell by binding with 3CL Mpro, ACE2 and complex, which suggest that XNJI may have a positive therapeutic effect on the neurological damage caused by SARS-CoV-2.

R285.5

国家自然科学基金资助项目（81573941）；湖南中医药大学中医学国内一流建设学科