背景:小青龙汤(XQLD)已被证明可有效治疗2019年严重冠状病毒病(COVID-19)病例;但是,机制尚不清楚。
目的:在本研究中,我们利用网络药理学和分子对接技术来鉴定有效成分,潜在目标,XQLD抗COVID-19的生物学途径。
方法:搜索公共数据库以确定XQLD和COVID-19相关靶标的活性化合物的假定靶标。利用STRING和Cytoscape建立蛋白质-蛋白质相互作用网络和药物组分,以及目标途径网络。DAVID数据库用于丰富生物学功能和信号通路。AutoDockVina用于虚拟对接。
结果:我们确定了138种活性化合物和259种XQLD的推定目标。生物网络分析显示槲皮素,β-谷甾醇,山奈酚,豆甾醇,木犀草素可能是XQLD的关键成分,而VEGFA,IL-6、MAPK3、CASS3、STAT3、MAPK1、MAPK8、CASP8、CCL2和FOS可能是候选药物靶点。富集分析表明,XQLD可以通过调节病毒防御来发挥作用,炎症反应,免疫反应,和凋亡。分子对接结果显示关键成分与宿主细胞靶蛋白之间的高亲和力。
结论:本研究揭示了XQLD抗COVID-19的潜在药理机制。这些发现为促进开发针对严重急性呼吸道综合症冠状病毒-2感染的新药奠定了坚实的基础,并可能有助于全球抗击COVID-19大流行。
BACKGROUND: A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear.
OBJECTIVE: In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19.
METHODS: Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking.
RESULTS: We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins.
CONCLUSIONS: This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.