目的 探讨针对新型冠状病毒肺炎（COVID-19）以人血管紧张素转换酶Ⅱ（ACE2）为治疗靶点的5味中药的作用机制。方法 通过传统中药系统药理学数据库和分析平台（TCMSP）筛选针对以ACE2为药物靶点的潜在中药，并进一步使用TCMSP平台分别查询潜在中药所含的相关成分及各自对应的药物靶点，利用STRING在线数据库对上述蛋白靶点进行蛋白互作分析并下载相关数据，进而通过CytoScape 3.2.1软件中的MCODE插件筛选处于PPI网络体系中的核心子网络模块。使用在线富集分析软件DAVID v6.8进行基因本体（GO）功能富集分析和基于京都基因与基因组百科全书（KEGG）通路富集分析，预测5味中药的药理作用机制，并在中医理论体系下验证并探讨候选药物配伍及临床应用的可行性。结果 通过TCMSP平台筛选出了5味以ACE2为治疗靶点并具备多重治疗作用的中药，即柴胡、葛根、葛花、川牛膝、萱草根。它们共包含42个潜在活性成分和240个药物作用靶点。这些靶点的GO生物功能和KEGG通路富集分析结果表明上述5种中药能够影响炎性反应、细胞凋亡与增殖等生物学过程，并与PI3K-Akt、TNF、FoxO和MAPK等信号通路密切相关。传统中医理论中柴胡、葛根药对是治疗传染性热病的经典药对；柴葛解肌汤在古今临床中亦大量应用于外感发热疾病并取得良好临床疗效，其主治的发热性疾病为六经辨证中的三阳合病，符合此次新型冠状病毒感染早期轻症患者的中医临床辩证，可予牛膝、萱草根加减化裁使用。结论 上述5种中药在COVID-19治疗方面具备有多靶点、多功能、多途径的药理作用，结合中医理论分析及既往临床经验，建议可探索性应用柴葛解肌汤加减或柴胡、葛根药对配伍治疗COVID-19。

Objective To explore the action mechanism of five Chinese medicines targeting ACE2 for the treatment of COVID-19. Methods Chinese medicines with human angiotensin converting enzyme Ⅱ (ACE2) targeting activity were screened through the traditional Chinese medicine (TCM) system pharmacology database and analysis platform (TCMSP), and the TCMSP platform was further utilized to identify the active ingredients of Chinese medicines and their corresponding drug targets. Then, the protein interaction of the above protein targets was analyzed by STRING online database and the relevant data were downloaded. Next, the core sub-network modules in the PPI network system were screened through the MCODE plug-in in CytoScape 3.2.1 software. The functional enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) were carried out, using online enrichment analysis software DAVID v6.8, to predict the pharmacological mechanism of the above five Chinese medicines, and to verify and explore the feasibility of compatibility and clinical application of related herb-pair or formula under the theoretical system of TCM. Results Five Chinese medicines with potential therapeutic effects on ACE2 were selected through the TCMSP platform, namely Bupleuri Radix, Puerariae Lobatae Radix, Puerariae Lobatae Flos, Cyathulae Radix, and Hemerocallis Radix, which contained 42 active ingredients and 240 drug targets. The results of GO biological function enrichment analysis showed that the above five Chinese medicines could affect the biological processes such as inflammatory response, cell apoptosis and proliferation and etc. The results of KEGG pathway enrichment analysis showed that the pharmacological mechanisms of these Chinese medicines were closely related to PI3K-Akt pathway, TNF pathway, FoxO pathway, MAPK pathway, and so on. In TCM theory, Bupleuri Radix and Puerariae Lobatae Radix is a classic herb-pair for the treatment of infectious and febrile diseases. Chaige Jieji Decoction is widely used in febrile diseases in ancient and modern clinics, and has achieved good clinical effects. The main febrile disease treated by this herb-pair is the triple-yang combination of diseases in the syndrome differentiation of the six meridians, which is in line with the syndrome differentiation of TCM in patients with SARS-CoV-2 infection. It can be used with Cyathulae Radix and Hemerocallis Radix in addition and subtraction. Conclusion The identified five Chinese medicines have multi-target, multi-function and multi-pathway pharmacological effects on the treatment of COVID-19. According to the theoretical analysis of TCM and previous clinical experience, it is suggested that Chaige Jieji Decoction or Bupleuri Radix and Puerariae Lobatae Radix herb-pair can be used to treat COVID-19.

R285.5

国家自然科学基金面上项目（81572416）