School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Chinese Medicine Plant Essential Oil Zhejiang Engineering Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Math Biosci Eng. 2022 Apr 6;19(6):5772-5792. doi: 10.3934/mbe.2022270.
The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the 2019 coronavirus disease (COVID-19), which has killed more than 4.5 million people. SARS-CoV-2 causes severe respiratory distress syndrome by targeting the lungs and also induces myocardial damage. Shenshao Ningxin Yin (SNY) has been used for more than 700 years to treat influenza. Previous randomized controlled trials (RCTs) have demonstrated that SNY can improve the clinical symptoms of viral myocarditis, reverse arrhythmia, and reduce the level of myocardial damage markers.
This work uses a rational computational strategy to identify existing drug molecules that target host pathways for the treatment of COVID-19 with myocarditis. Disease and drug targets were input into the STRING database to construct proteinɃprotein interaction networks. The Metascape database was used for GO and KEGG enrichment analysis.
SNY signaling modulated the pathways of coronavirus disease, including COVID-19, Ras signaling, viral myocarditis, and TNF signaling pathways. Tumor necrosis factor (TNF), cellular tumor antigen p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), and the signal transducer and activator of transcription 3 (STAT3) were the pivotal targets of SNY. The components of SNY bound well with the pivotal targets, indicating there were potential biological activities.
Our findings reveal the pharmacological role and molecular mechanism of SNY for the treatment of COVID-19 with myocarditis. We also, for the first time, demonstrate that SNY displays multi-component, multi-target, and multi-pathway characteristics with a complex mechanism of action.
新发现的β冠状病毒 SARS-CoV-2 是导致 2019 年冠状病毒病（COVID-19）的病原体，该病已导致超过 450 万人死亡。SARS-CoV-2 通过靶向肺部引起严重的呼吸窘迫综合征，还会导致心肌损伤。参芍宁心饮（SNY）已用于治疗流感超过 700 年。以前的随机对照试验（RCT）表明，SNY 可以改善病毒性心肌炎的临床症状，逆转心律失常并降低心肌损伤标志物的水平。
这项工作使用合理的计算策略来鉴定针对 COVID-19 合并心肌炎的宿主途径的现有药物分子。将疾病和药物靶点输入 STRING 数据库以构建蛋白质-蛋白质相互作用网络。使用 Metascape 数据库进行 GO 和 KEGG 富集分析。
SNY 信号调节了冠状病毒病的途径，包括 COVID-19、Ras 信号、病毒性心肌炎和 TNF 信号通路。肿瘤坏死因子（TNF）、细胞肿瘤抗原 p53（TP53）、丝裂原激活的蛋白激酶 1（MAPK1）和信号转导和转录激活因子 3（STAT3）是 SNY 的关键靶点。SNY 的成分与关键靶标结合良好，表明存在潜在的生物学活性。
我们的研究结果揭示了 SNY 治疗 COVID-19 合并心肌炎的药理作用和分子机制。我们还首次证明，SNY 具有多成分、多靶点和多途径的特征，具有复杂的作用机制。
