目的 探尋連花清瘟方抗冠狀病毒的物質(zhì)基礎(chǔ)及作用機(jī)制，為新型冠狀病毒肺炎（COVID-19）的中醫(yī)藥治療提供參考。方法 借助TCMSP、Batman、Swiss Target Prediction等數(shù)據(jù)庫檢索連花清瘟方中藥味的化學(xué)成分和作用靶點(diǎn)。通過GeneCards篩選出冠狀病毒的疾病靶點(diǎn)。使用Cytoscape軟件構(gòu)建“藥物-成分-靶點(diǎn)-疾病”網(wǎng)絡(luò)和潛在靶點(diǎn)的相互作用關(guān)系，通過富集分析預(yù)測作用機(jī)制，并將連花清瘟方的主要活性成分與新型冠狀病毒（SARS-CoV-2）3CL水解酶（Mpro）、血管緊張素轉(zhuǎn)化酶II（ACE2）進(jìn)行分子對接驗(yàn)證。結(jié)果 挖掘出連花清瘟方中100種活性成分、636個藥物靶點(diǎn)，冠狀病毒347個疾病靶點(diǎn)，得到藥物-疾病共同靶點(diǎn)67個，關(guān)鍵靶點(diǎn)涉及PTGS2、IL6、CASP3、MAPK1、EGFR、ACE2等。GO富集分析共得到條目1 946個，主要涉及T細(xì)胞活化、病毒受體、炎癥反應(yīng)等。KEGG通路富集篩選出166條信號通路，包括腎素-血管緊張素系統(tǒng)、Toll樣受體信號通路、JAK-STAT信號通路、T細(xì)胞受體信號通路、TNF信號通路等。分子對接結(jié)果顯示山柰酚、槲皮素、木犀草素與Mpro有較好的結(jié)合能力；甘草次酸、豆甾醇、靛藍(lán)與ACE2有較好的結(jié)合能力。結(jié)論 連花清瘟方可通過多成分、多靶點(diǎn)、多通路作用于冠狀病毒，其主要成分與Mpro、ACE2有較好的結(jié)合能力，從而可能對COVID-19有治療作用。

Objective To explore the active compounds and mechanism of Lianhua Qingwen Prescription for the treatment of coronavirus, and provide a reference for the treatment of COVID-19. Methods With the help of TCMSP, Batman, Swiss Target Prediction and other databases, the chemical constituents and targets of Lianhua Qingwen Prescription were retrieved. Coronavirus disease targets were screened by GeneCards. Cytoscape software was used to construct a "drug-component-target-disease" interaction network map and potential target interactions, and the action mechanism was predicted through enrichment analysis. The main active ingredients of Lianhua Qingwen Prescription were verified by molecular docking with Mpro and ACE2. Results A total of 100 active ingredients, 636 drug targets, and 347 disease targets were excavated, and 67 drug-disease common targets were obtained. The key targets involved PTGS2, IL6, CASP3, MAPK1, EGFR, ACE2, etc. A total of 1 946 entries were obtained by GO enrichment analysis, which mainly involved T cell activation, viral receptors, and inflammatory responses. KEGG pathway enrichment screened 166 signaling pathways, including renin-angiotensin system, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, T cell receptor signaling pathway, TNF signaling pathway and so on. The molecular docking results showed that kaempferol, quercetin and luteolin had good binding ability with Mpro; And glycyrrhetinic acid, stigmasterol, indigo had good binding ability with ACE2. Conclusion Lianhua Qingwen Prescription acts on coronavirus through multiple components, multiple targets, and multiple pathways. The main components have good binding ability with Mpro and ACE2, so as to have a therapeutic effect on COVID-19.

R285

國家自然科學(xué)基金資助項(xiàng)目（81873340）