School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
The First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, China.
Drug Dev Ind Pharm. 2020 Aug;46(8):1345-1353. doi: 10.1080/03639045.2020.1788070. Epub 2020 Jul 8.
Huashi Baidu formula (HSBDF) was developed to treat the patients with severe COVID-19 in China. The purpose of this study was to explore its active compounds and demonstrate its mechanisms against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through network pharmacology and molecular docking.
All the components of HSBDF were retrieved from the pharmacology database of TCM system. The genes corresponding to the targets were retrieved using UniProt and GeneCards database. The herb-compound-target network was constructed by Cytoscape. The target protein-protein interaction network was built using STRING database. The core targets of HSBDF were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HSBDF were docked with SARS-CoV-2 and angiotensin converting enzyme II (ACE2).
Compound-target network mainly contained 178 compounds and 272 corresponding targets. Key targets contained MAPK3, MAPK8, TP53, CASP3, IL6, TNF, MAPK1, CCL2, PTGS2, etc. There were 522 GO items in GO enrichment analysis ( < .05) and 168 signaling pathways ( < .05) in KEGG, mainly including TNF signaling pathway, PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, and HIF-1 signaling pathway. The results of molecular docking showed that baicalein and quercetin were the top two compounds of HSBDF, which had high affinity with ACE2.
Baicalein and quercetin in HSBDF may regulate multiple signaling pathways through ACE2, which might play a therapeutic role on COVID-19.
化湿败毒方（HSBDF）是在中国开发用于治疗重症 COVID-19 患者的方剂。本研究旨在通过网络药理学和分子对接方法探索其活性化合物，并证明其对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的作用机制。
从中药系统药理学数据库中检索 HSBDF 的所有成分。使用 UniProt 和 GeneCards 数据库检索与靶点相对应的基因。使用 Cytoscape 构建草药-化合物-靶点网络。使用 STRING 数据库构建靶点蛋白-蛋白相互作用网络。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析 HSBDF 的核心靶点。使用分子对接方法将 HSBDF 的主要活性化合物与 SARS-CoV-2 和血管紧张素转换酶 II（ACE2）对接。
化合物-靶点网络主要包含 178 种化合物和 272 个对应靶点。关键靶点包含 MAPK3、MAPK8、TP53、CASP3、IL6、TNF、MAPK1、CCL2、PTGS2 等。GO 富集分析中有 522 个 GO 条目（ < .05），KEGG 中有 168 个信号通路（ < .05），主要包括 TNF 信号通路、PI3K-Akt 信号通路、NOD 样受体信号通路、MAPK 信号通路和 HIF-1 信号通路。分子对接结果表明，黄芩苷和槲皮素是 HSBDF 的前两种化合物，与 ACE2 具有高亲和力。
HSBDF 中的黄芩苷和槲皮素可能通过 ACE2 调节多种信号通路，从而在 COVID-19 中发挥治疗作用。
