海南医科大学学报

目的:探讨宣肺败毒方治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法:借助中药系统药理学分析平台(TCMSP)检索宣肺败毒方有效活性成分及作用靶标,运用GeneCards等数据库获取COVID-19的相关靶标基因并与宣肺败毒方的作用靶标取交集获取治疗靶标。将治疗靶标上传STRING数据库获取蛋白交互作用(PPI)信息,利用Cytoscape构建药物-靶点-疾病网络、靶点蛋白高置信度PPI网络、活性成分-靶点-通路网络。利用Bioconductor中的R包对潜在作用靶点进行GO功能分析和KEGG通路富集分析。将主要活性成分分别与SARS-CoV-2的3CL水解酶(3CLPro)和血管紧张素转换酶2(ACE2)及关键靶标进行分子对接。结果:筛选出宣肺败毒方有效活性成分共99个,其中作用于COVID-19的22个活性成分可通过52个潜在靶标作用于COVID-19。富集得到GO中1 364个生物过程条目和22条KEGG通路,涉及IL-17、JAK-STAT、MAPK、NF-κB、PI3K-Akt、Th1和Th2细胞分化、Th17细胞分化、T细胞受体、血管内皮生长因子(VEGF)和沙门氏菌感染等路径。分子对接结果显示宣肺败毒方中的木犀草素、β-谷甾醇、芒柄花黄素、紫檀素等活性成分与3CLPro和ACE2有较好的结合性,并且与核心靶点也有较好的结合性。结论:宣肺败毒方主要通过黄酮类和植物淄醇类活性成分与SARS-CoV-2的ACE2和3CLPro受体结合,抑制病毒入侵及病毒复制,在病毒感染细胞后可能通过调节IL-6、MAPK3、MAPK1、IL-1β、CCL2、EGFR、NOS2等关键靶点发挥抗炎、抗细胞因子风暴、抗氧化、调节机体免疫的作用来治疗COVID-19。

Objective: To investigate the potential mechanism of Xuanfei Baidu Formula in treating coronavirus disease 2019(COVID-19). Methods: Traditional Chinese Medicine Systems Pharmacology was employed to search the effective active component and targets of Xuanfei Baidu Formula. Databases, GeneCards etc. were employed to obtain the relevant target genes of COVID-19 and intersect with the targets of Xuanfei Baidu Formula to obtain the therapeutic targets. The therapeutic targets were uploaded to the STRING database to obtain protein interaction information, and Cytoscape was utilized to construct drug-target-disease networks, high-confidence protein interaction information networks for target proteins, and active-target-pathway networks. GO, gene ontology, functional analysis and KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of potential targets of action were performed using the R package in Bioconductor. The main active components were molecular docking technology with 3 C-like protease(3 CLPro) and angiotensin-cinverting enzyme2(ACE2) and key targets of SARS-CoV-2, respectively. Results: A total of 99 effective active ingredients of Xuanfei Baidu Formula were selected, of which 22 active ingredients acting on COVID-19 could act on COVID-19 through 52 potential targets. Enrichment yielded 1 364 biological process entries and 22 KEGG pathways in GO, involving paths such as IL-17, JAK-STAT, MAPK, NF-κB, PI3 K-Akt, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor, vascular endothelial growth factor and Salmonella infection. Molecular docking technology results revealed that active components such as luteolin, beta-sitostero, formononetin, and shinpterocarpin in Xuanfei Baidu Formula embraced satisfactory binding to 3 CLPro and ACE2, and also had good binding to core targets. Conclusions: Xuanfei Baidu Formula inhibits viral invasion and viral replication mainly by binding to ACE2 and 3 CLPro receptors of SARS-CoV-2 through flavonoids and phytosterols, and may play a role in the treatment of COVID-19 by regulating key targets such as IL6, MAPK3, MAPK1, IL1β, CCL2, EGFR, and NOS2 after virus infection of cells, exerting anti-cytokine storm, anti-oxidation, and regulating the body's immunity.