目的 以網(wǎng)絡藥理學和分子對接法探索肺毒清治療新型冠狀病毒肺炎（COVID-19）活性化合物。方法 利用中藥系統(tǒng)藥理學分析平臺（TCMSP）獲得肺毒清中木蝴蝶、梔子及苦參3味中藥相關(guān)的成分和作用靶點，通過UniProt數(shù)據(jù)庫查詢靶點對應的基因；采用STRING平臺構(gòu)建靶點PPI網(wǎng)絡；通過DAVID進行GO（gene ontology）生物過程及KEGG（Kyoto encyclopedia of genes and genomes）通路富集分析，對核心靶點進行網(wǎng)絡拓撲分析，運用Cytoscape 3.7.0構(gòu)建成分-靶點網(wǎng)絡，分析預測其作用機制。肺毒清中核心化合物與新型冠狀病毒（SARS-CoV-2）3CL水解酶進行分子對接，同時將結(jié)合能最低的前3位化合物與血管緊張素轉(zhuǎn)化酶II（ACE2）進行分子對接。結(jié)果 成分-靶點網(wǎng)絡得到269個節(jié)點，4 204條邊，其中包括槲皮素、β-谷甾醇、山柰酚等50個成分，關(guān)鍵靶點有JUN、AKT1、TP53、PTGS2、FOS、ESR1等。GO功能富集分析得到GO條目2 187個（P<0.05），其中生物過程（biological process，BP）條目1 877個，細胞組成（cellular component，CC）條目105個，分子功能（molecular function，MF）條目205個；KEGG富集篩選得到25條信號通路（P<0.05），主要有乙型肝炎通路、致癌通路、腫瘤壞死因子信號通路、胰腺癌、弓形蟲病通路等；木犀草素（-26.78 kJ/mol）、槲皮素（-26.36 kJ/mol）、去甲脫水淫羊藿黃素（-25.94 kJ/mol）作用于SARS-CoV-2 3CL水解酶的分子對接結(jié)合能最低。結(jié)論 肺毒清的活性化合物通過作用于JUN、AKT1、TP53、PTGS2、FOS、ESR1等靶點，與ACE2結(jié)合，調(diào)節(jié)多條信號通路，對COVID-19有潛在治療作用。

Objective To explore the active compounds of Feiduqing in the treatment of coronavirus disease 2019 (COVID-19) pneumonia. Methods The Chinese medicine system pharmacology analysis platform (TCMSP) was used to obtain the three Chinese medicine-related components and targets of Oroxylum indicum, Gardenia jasminoides and Sophora flavescens of Feiduqing, and the genes corresponding to the targets were queried through the UniProt database. The STRING platform was used to build the target PPI network. DAVID was used to perform GO biological processes and KEGG pathway enrichment analysis was used to perform network topology analysis on core targets. Cytoscape 3.7.0 was used to construct a component-target network analysis to predict the mechanism of Feiduqing. The core active compound of Feiduqing was molecularly docked with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL hydrolase, and the first three compounds with the lowest binding energy were docked with angiotensin converting enzyme II (ACE2). Results The component-target network included 269 nodes and 4 204 edges, including 50 components such as quercetin, beta-sitosterol, kaempferol, etc, and key targets included JUN, AKT1, TP53, PTGS2, FOS, ESR1, etc. The function enrichment analysis of GO yielded 2 187 (P<0.05), including 1 877 biological process (BP) entries, 105 cellular components (CC) entries, and 205 molecular functions (MF) entries. Twenty-five signal pathways were screened by KEGG enrichment analysis (P<0.05), mainly including hepatitis B, pathways in cancer, TNF signaling pathway, pancreatic cancer, toxoplasmosis pathway, etc. The active ingredients with the lowest molecular docking binding energy acting on SARS-CoV-2 3CL hydrolase were luteolin (-26.78 kJ/mol), quercetin (-26.36 kJ/mol), 8-prenyl-kaempferol (-25.94 kJ/mol). Conclusion The active compound of Feiduqing may have a therapeutic effect on COVID-19 through the action on targets such as JUN, AKT1, TP53, PTGS2, FOS, ESR1, binding with angiotensin converting enzyme II (ACE2) and regulating many signaling pathways.

R285

四川省科學技術(shù)廳2020年省級科技計劃項目（20YYJC1839）；2020年成都龍泉驛區(qū)科技計劃項目（新型冠狀病毒感染的肺炎疫情防控專項）