基于网络药理学和分子对接探讨散寒化湿宣肺方抗新型冠状病毒活性化合物的初步研究

A Preliminary Study on Anti-SARS-CoV-2 Active Compound of Sanhan Huashi Xuanfei Formula Based on Network Pharmacology and Molecular Docking

目的探寻散寒化湿宣肺方(SHXF)中抗新型冠状病毒(SARS-CoV-2)的活性化合物。方法借助TC⁃MSP等数据库检索SHXF方中苍术、陈皮、厚朴、藿香、草果、生麻黄、羌活、生姜、槟榔所含化学成分与作用靶点。通过Cytoscape软件绘制化合物-靶点网络图和PPI网络图对化合物和靶点进行拓扑分析。采用DAVID 6.7数据库对靶点进行GO功能和KEGG通路富集分析;利用AutoDock Vina对SHXF关键化合物与SARSCoV-23CL水解酶和Nsp15蛋白进行分子对接。结果经筛选获得SHXF共85个活性化合物与214个作用靶点,关键靶点涉及Akt1、IL-6、MAPK3、VEGFA、JUN等。GO富集分析得到功能条目599个(P<0.05),其中生物过程(BP)460个,细胞组成(CC)55个,分子功能(MF)84个。KEGG通路获得113条(P<0.05),主要涉及甲型流感(Influenza A)信号通路、TLR(Toll-like receptor)信号通路、PI3K-Akt信号通路、HIF-1信号通路等。分子对接结果显示SHXF中槲皮素、柚皮素、谷甾醇等核心化合物与瑞德西韦等推荐用药亲和力相似。结论SHXF中的槲皮素、柚皮素、谷甾醇等核心化合物可与SARS-CoV-23CL水解酶和Nsp15蛋白结合,或为治疗新型冠状病毒肺炎的活性化合物。

Objective:To investigate the anti-SARS-CoV-2 active compounds in Sanhan Huashi Xuanfei For⁃mula(SHXF).Methods:The main ingredients and potential targets in nine kinds of Chinese medicine,such as Atractylodes rhizome,dried tangerine peel,officinal magnolia bark,Agastache rugosus,fruit of caoguo,raw ephedra,incised Notopterygium rhizome and root,fresh ginger and areca seed in SHXF were collected from TCMSP data⁃base.Topological analysis of compounds,compact-target network graph,and PPI network graph were carried out by Cytoscape software.DAVID 6.7 database was applied to analyze the GO function and the enrichment of the KEGG pathway.Autodock Vina was used to docking compounds screened from SHXF with SARS-CoV-23CL hy⁃drolase and Nsp15 protein.Results:A total of 85 active compounds and 214 action targets of SHXF were screened,and the key targets involved Akt1,IL-6,MAPK3,VEGFA,JUN,etc.GO enrichment analysis yielded 599 functional items(P<0.05),including 460 biological processes(BP),55 cell composition(CC)and 84 molecu⁃lar functions(MF).A total of 113 KEGG pathways were obtained(P<0.05),including the influenza A signaling pathway,toll-like receptor signaling pathway,PI3K-Akt signaling pathway,hypoxia inducible factor-1 signaling pathway,etc.The results of molecular docking showed that the core compounds such as quercetin,naringin and si⁃tosterol in SHXF had similar affinity with the recommended drug remdesivir.Conclusion:The core compounds such as quercetin,naringin and sitosterol in SHXF can bind to SARS-CoV-23CL hydrolase and Nsp15 protein,or be active compounds in the treatment of COVID 2019.