An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology

基于药代动力学、代谢组学及分子对接技术综合分析清肺排毒汤在寒湿环境下抗HCoV-229E作用机制

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作者:Yan Zhang, Xinru Gu, Yanyan Zhou, Nan Si, Wenya Gao, Bo Sun, Jing Sun, Tao Li, Linna Wang, Xiaolu Wei, Shanshan Guo, Xiaolan Cui, Baolin Bian, Hongjie Wang, Liang Wang, Haiyu Zhao

Background

The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear.

Conclusion

In the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation.

Methods

Firstly, the pharmacokinetic study of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned

Purpose

An integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification.

Results

According to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well.

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