以血管紧张素转换酶Ⅱ(ACE2）为受体挖掘治疗新型冠状病毒肺炎（COVID-19）潜在中药及单体成分

目的以血管紧张素转换酶Ⅱ(ACE2)为受体探讨中药及单体成分治疗新型冠状病毒肺炎(COVID-19)的作用机制。方法借助中药系统药理学分析平台(TCMSP)检索作用于ACE2受体的中药及单体成分。通过UniProt、GeneCards等数据库查询中药单体成分作用靶点对应的基因名,进而运用Cytoscape 3.6.1构建化合物-靶点(基因)网络,通过DAVID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,预测其作用机制。结果葛根素-靶点网络中靶点54个,关键靶点涉及AKT1、VEGFA、TNF等。GO功能富集分析得到GO条目554个(P0.05),其中生物过程(BP)条目486个,细胞组成(CC)条目26个,分子功能(MF)条目42个。KEGG通路富集筛选得到162条信号通路(P0.05),涉及小细胞肺癌、非小细胞肺癌、肾素-血管紧张素系统通路等。分子对接结果显示葛根素与ACE2和新型冠状病毒(SARS-CoV-2)水解酶的亲和力与推荐用药相近。结论葛根素与ACE2结合作用于AGTR1、NOS3、HIF1A等靶点调节多条信号通路,从而可能对COVID-19有治疗作用。

Investigation of potential Chinese materia medica and its monomers in treatment of coronavirus disease 2019 (COVID-19) based on angiotensin converting enzyme II (ACE2) receptor

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.