Cai Yu, Zeng Min, Chen Yun-Zhong
College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China; Institute of Engineering Technology of Chinese Traditional Medicine and Health Food of Hubei Province, Wuhan, China.
Ann Palliat Med. 2021 Apr;10(4):3864-3895. doi: 10.21037/apm-20-1759. Epub 2021 Mar 8.
Huashi Baidu Formula (HSBDF) is a traditional Chinese medicine formula consisting of fourteen parts, which has been proven effective for treating coronavirus disease 2019 (COVID-19) clinically. However, the therapeutic mechanism of the effect of HSBDF on COVID-19 remains unclear.
The components and action targets of HSBDF were searched in the TCMSP, YaTCM, PubChem, and TargetNet databases. Disease targets related to ACE2 were screened in single-cell sequence data of colon epithelial cells from other reports. The therapeutic targets of HSBDF for COVID-19 were obtained by integrated analysis, and the protein-protein interaction was analyzed using the STRING database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) processes were analyzed using the OmicsBean and Metascape databases. The communication between networks [component-target (C-T) network, component-target-pathway (C-T-P) network, herb-target (H-T) network, target-pathway (T-P) network, and meridian-tropism (M-T) network] was constructed by Cytoscape software. The Cloud computing molecular docking platform was used to verify the molecular docking.
The obtained 223 active ingredients and 358 targets of HSBDF. The 5,555 COVID-19 disease targets related to ACE2 were extracted, and 84 compound-disease common targets were found, of which the principal targets included ACE, ESR1, ADRA1A, and HDAC1. A total of 3,946 items were seized by GO enrichment analysis, mainly related to metabolism, protein binding, cellular response to the stimulus, and receptor activity. The enriched KEGG pathways screened 46 signaling pathways, including the renin-angiotensin system, the renin secretion, NF-kappa B pathway, the arachidonic acid metabolism, and the AMPK signaling pathway. The molecular docking results showed that the bioactive components of HSBDF have an excellent binding ability with main proteins related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
HSBDF might act on SARS-CoV-2 through multiple components, targets, and pathways. Here we reveal preliminary results of the mechanism of action of HSBDF on SARS-CoV-2, providing a theoretical basis for future clinical applications.
化湿败毒方是一种由十四味药组成的中药方剂，临床已证实其对治疗新型冠状病毒肺炎（COVID-19）有效。然而，化湿败毒方治疗COVID-19的作用机制仍不清楚。
在中药系统药理学数据库与分析平台（TCMSP）、中药综合数据库（YaTCM）、化学物质数据库（PubChem）和靶点网络数据库（TargetNet）中检索化湿败毒方的成分及作用靶点。从其他报道的结肠上皮细胞单细胞测序数据中筛选与血管紧张素转换酶2（ACE2）相关的疾病靶点。通过综合分析获得化湿败毒方治疗COVID-19的作用靶点，并使用STRING数据库分析蛋白质-蛋白质相互作用。使用OmicsBean和Metascape数据库分析基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路。通过Cytoscape软件构建网络间的联系[成分-靶点（C-T）网络、成分-靶点-通路（C-T-P）网络、中药-靶点（H-T）网络、靶点-通路（T-P）网络和归经（M-T）网络]。使用云计算分子对接平台验证分子对接。
获得化湿败毒方223种活性成分和358个靶点。提取与ACE2相关的5555个COVID-19疾病靶点，发现84个化合物-疾病共同靶点，其中主要靶点包括ACE、雌激素受体1（ESR1）、α1A-肾上腺素能受体（ADRA1A）和组蛋白去乙酰化酶1（HDAC1）。通过GO富集分析共获得3946项，主要与代谢、蛋白质结合、细胞对刺激的反应和受体活性相关。富集的KEGG通路筛选出46条信号通路，包括肾素-血管紧张素系统、肾素分泌、核因子κB通路、花生四烯酸代谢和腺苷酸活化蛋白激酶（AMPK）信号通路。分子对接结果表明，化湿败毒方的生物活性成分与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）相关主要蛋白具有良好的结合能力。
化湿败毒方可能通过多种成分、靶点和通路作用于SARS-CoV-2。在此，我们揭示了化湿败毒方对SARS-CoV-2作用机制的初步结果，为其未来临床应用提供理论依据。
