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Journal of Integrative Medicine ›› 2020, Vol. 18 ›› Issue (3): 229-241.doi: 10.1016/j.joim.2020.03.004

• Original Experimental Research • Previous Articles     Next Articles

Active constituents and mechanisms of Respiratory Detox Shot, a traditional Chinese medicine prescription, for COVID-19 control and prevention: network-molecular docking-LC-MSE analysis

Zi-jia Zhanga, Wen-yong Wua,b, Jin-jun Houa, Lin-lin Zhanga, Fei-fei Lia,b, Lei Gaoa,b, Xing-dong Wua, Jing-ying Shia,b, Rong Zhanga,b, Hua-li Longa, Min Leia, Wan-ying Wua, De-an Guoa, Kai-xian Chena, Lewis A. Hofmannc, Zhonghua Cic   

  1. a Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
    b University of Chinese Academy of Sciences, Beijing 100049, China
    c World Health Science Organization, Virginia Leesburg 20176, USA
  • Received:2020-03-13 Accepted:2020-03-17 Online:2020-05-08 Published:2020-03-20
  • About author:Zi-jia Zhang, Wen-yong Wu and Jin-jun Hou made equal contribution to this work.
  • Supported by:

    We are grateful for the financial support from National Key Research and Development Program of China (No. 2018YFC1707900)

Objective 

The Lung-toxin Dispelling Formula No.1 (referred to as Respiratory Detox Shot, RDS) was established based on the theory of traditional Chinese medicine (TCM) medicinal properties and the classical prescription of TCM. It has demonstrated therapeutic benefits in both disease control and prevention in the effort to contain corona virus disease 2019 (COVID-19). However, the material basis and action mechanism of RDS are still unclear. The goal of the study is to clarify the material foundation and action mechanism of RDS.

Methods 

To achieve in-depth analyses of RDS from a holistic perspective, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, cluster analysis, and the hub genes involved in the disease pathways were identified, and their corresponding compounds were further applied to molecular docking for in vitro biological validation. The presence of the validated compounds was also measured to demonstrate the material basis of RDS. In our network pharmacology study, a total of 26 bioinformatic software and databases were accessed, and 6 networks covering the entire Zang-fu viscera were constructed to achieve comprehensive analysis and visualization of the intricate connections among the compounds-targets-disease pathway-meridians of RDS.

Results 

For all 1071 compounds of 9 ingredients of RDS from established TCM databases, 157 compounds passed drug-likeness screening and led to 339 predicted targets in the compound-target network. 42 hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-compound-disease network. Twelve disease pathways attributed to Lung-Large intestine meridian, with 6 and 5 to Kidney-Urinary bladder and Stomach-Spleen meridians, respectively. 118 candidate compounds showed a high binding affinity with SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) by molecular docking using computational pattern recognition. The in vitro activity of 22 compounds was validated by the 3CLpro inhibition assay. Finally, using the technique of liquid chromatography mass spectrometry in data-independent analysis mode, 7 out of 22 compounds were confirmed and validated in RDS aqueous decoction with reference standards in both non-targeted and targeted approaches.

Conclusion 

Our results unveiled that RDS acts primarily in the Lung-Large intestine, Kidney-Urinary bladder, and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all 9 ingredients. Integrated with the context of TCM meridian theory, multiple components and targets of RDS demonstrate the action dual effects of health-strengthening and pathogen-eliminating in one prescription to achieve systemic therapeutic effects for early COVID-19 control and prevention.

Key words: Lung-toxin Dispelling Formula No.1, COVID-19, Severe acute respiratory syndrome coronavirus 2, 3C-like protease, SARS coronavirus, Network pharmacology, Molecular docking molecular docking, LC-MSE, Meridian tropism, Zang-fu (viscera)

[1] Arthur Yin Fan, Sherman Gu, Sarah Faggert Alemi, Research Group for Evidence-based Chinese Medicine. Chinese herbal medicine for COVID-19: Current evidence with systematic review and meta-analysis. Journal of Integrative Medicine, 2020, 18(5): 385-394.
[2] Jian-zhong Dang, Gang-yan Zhu, Ying-jie Yang, Fang Zheng. Clinical characteristics of coronavirus disease 2019 in patients aged 80 years and older. Journal of Integrative Medicine, 2020, 18(5): 395-400.
[3] Deng-hai Zhang, Kun-lun Wu, Xue Zhang, Sheng-qiong Deng, Bin Peng. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. Journal of Integrative Medicine, 2020, 18(2): 152-158.
[4] Chang-quan Ling. Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2). Journal of Integrative Medicine, 2020, 18(2): 87-88.
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