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Journal of Integrative Medicine ›› 2022, Vol. 20 ›› Issue (6): 561-574.doi: 10.1016/j.joim.2022.07.005

Special Issue: COVID-19

• Original Experimental Research • Previous Articles     Next Articles

Analysis of mechanisms of Shenhuang Granule in treating severe COVID-19 based on network pharmacology and molecular docking

Xiang-ru Xua 1, Wen Zhanga 1, Xin-xin Wua, Hong-qiang Yanga, Yu-ting Suna, Yu-ting Pua, Bei Wanga, Wei Penga, Li-hua Suna, Quan Guoa, Shuang Zhoub, Bang-jiang Fanga,c   

  1. a. Department of Emergency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    b. Acupuncture and Massage College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    c. Institute of Critical Care, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2021-12-13 Accepted:2022-06-15 Online:2022-11-15 Published:2022-11-09
  • Contact: Shuang Zhou; E-mail address: Bang-jiang Fang; E-mail address:

Objective: Severe cases of coronavirus disease 2019 (COVID-19) are expected to have a worse prognosis than mild cases. Shenhuang Granule (SHG) has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial, but the active chemical constituents and underlying mechanisms of action remain unknown. The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19, using network pharmacology.
Methods: Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG. Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform, SwissTargetPrediction, and Gene Expression Omnibus (GEO) databases. The target protein-protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms. Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.
Results: Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets, including hub genes such as HSP90AA1, MMP9, CXCL8, PTGS2, IFNG, DNMT1, TYMS, MDM2, HDAC3 and ABCB1. Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction, calcium signaling pathway and cAMP signaling pathway. Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets. Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.
Conclusion: Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways; this provides a scientific basis for clinical applications and further experiments.

Key words: COVID-19, SARS-CoV-2, Shenhuang Granule, Mechanism, Network pharmacology, Molecular docking, Molecular dynamics simulation

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[3] Ting Zhang, Qing Zhang, Wei Zheng, Ting Tao, Ruo-lan Li, Li-yu Wang, Wei Peng, Chun-jie Wu. Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway: Network pharmacology and experimental validation. Journal of Integrative Medicine, 2022, 20(6): 543-560.
[4] Han-ting Wu, Cong-hua Ji, Rong-chen Dai, Pei-jie Hei, Juan Liang, Xia-qiu Wu, Qiu-shuang Li, Jun-chao Yang, Wei Maob, Qing Guo. Traditional Chinese medicine treatment for COVID-19: An overview of systematic reviews and meta-analyses. Journal of Integrative Medicine, 2022, 20(5): 416-426.
[5] Andréa D. Fuzimoto. An overview of the anti-SARS-CoV-2 properties of Artemisia annua, its antiviral action, protein-associated mechanisms, and repurposing for COVID-19 treatment. Journal of Integrative Medicine, 2021, 19(5): 375-388.
[6] 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.
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