[關鍵詞]
[摘要]
目的 以血管緊張素轉換酶II（ACE2）為受體探討中藥及單體成分治療新型冠狀病毒肺炎（COVID-19）的作用機制。方法 借助中藥系統(tǒng)藥理學分析平臺（TCMSP）檢索作用于ACE2受體的中藥及單體成分。通過UniProt、GeneCards等數(shù)據庫查詢中藥單體成分作用靶點對應的基因名，進而運用Cytoscape 3.6.1構建化合物-靶點（基因）網絡，通過DAVID進行基因本體（GO）功能富集分析和基于京都基因與基因組百科全書（KEGG）通路富集分析，預測其作用機制。結果 葛根素-靶點網絡中靶點54個，關鍵靶點涉及AKT1、VEGFA、TNF等。GO功能富集分析得到GO條目554個（P<0.05），其中生物過程（BP）條目486個，細胞組成（CC）條目26個，分子功能（MF）條目42個。KEGG通路富集篩選得到162條信號通路（P<0.05），涉及小細胞肺癌、非小細胞肺癌、腎素-血管緊張素系統(tǒng)通路等。分子對接結果顯示葛根素與ACE2和新型冠狀病毒（SARS-CoV-2）水解酶的親和力與推薦用藥相近。結論 葛根素與ACE2結合作用于AGTR1、NOS3、HIF1A等靶點調節(jié)多條信號通路，從而可能對COVID-19有治療作用。
[Key word]
[Abstract]
Objective To investigate the mechanism of treating COVID-19 with traditional Chinese medicine and monomers with ACE2 as receptor. Methods Chinese materia medica and monomers acting on angiotensin converting enzyme II (ACE2) receptor was retrieved by TCMSP database. UniProt, GeneCards and other databases were used to query the gene names corresponding to the target of Chinese medicine monomer, and then Cytoscape 3.6.1 was used to construct the compound-target (gene) network. DAVID was used to carry out the gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to predict its mechanism of action. Results There were 54 targets in the puerarin-target network, including AKT1, VEGFA, TNF, etc. GO function enrichment analysis revealed 554 GO items (P<0.05), including 486 biological process (BP) items, 26 cell component (CC) items, and 42 molecular function (MF) items. There were 162 signaling pathways (P<0.05) involved in small cell lung cancer, non-small cell lung cancer, renin-angiotensin system pathway, etc. The results of molecular docking showed that the affinity of puerarin with ACE2 and hydrolase of SARS-CoV-2 was similar to the recommended drugs. Conclusion Puerarin may regulate multiple signaling pathways by binding ACE2 to AGTR1, NOS3, HIF1A and other targets and regulating multiple signaling pathways, which may have therapeutic effects on COVID-19.
[中圖分類號]
R285.5
[基金項目]
江蘇省中醫(yī)藥領軍人才項目（SLJ0208）；蘇州市“科教興衛(wèi)”青年課題（KJXW2019044）；蘇州市科技局指導性課題（SYSD2019149）；蘇州市中醫(yī)醫(yī)院院級科技計劃項目（YQN2017004）
