Skip to main content

In Silico Screening of Potential Chinese Herbal Medicine Against COVID-19 by Targeting SARS-CoV-2 3CLpro and Angiotensin Converting Enzyme II Using Molecular Docking

Abstract

Objective

To seek potential Chinese herbal medicine (CHM) for the treatment of coronavirus disease 2019 (COVID-19) through the molecular docking of the medicine with SARS-CoV-2 3CL hydrolytic enzyme and the angiotensin converting enzyme II(ACE2) as receptors, using computer virtual screening technique, so as to provide a basis for combination forecasting.

Methods

The molecular docking of CHM with the SARS-Cov-2 3CL hydrolase and the ACE2 converting enzyme, which were taken as the targets, was achieved by the Autodock Vina software. The CHM monomers acting on 3CLpro and ACE2 receptors were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the active ingredients were selected, and the key CHMs and compounds were speculated. Based on the perspective of network pharmacology, the chemical-target network was constructed, and the functional enrichment analysis of gene ontology and the pathway enrichment analysis of Kyoto encyclopedia of genes and genomes were carried out by DAVID to speculate about the mechanism of action of the core drug pairs.

Results

There are 6 small molecule compounds that have the optimal binding energy with the two target proteins. Among 238 potential anti-COVID-19 herbs screened in total, 16 kinds of CHM containing the most active ingredients, and 5 candidate anti-COVID-19 herbs that had been used in high frequency, as well as a core drug pair, namely, Forsythiae Fructus-Lonicerae Japonicae Flos were selected.

Conclusion

The core drug pair of Forsythiae Fructus-Lonicerae Japonicae Flos containing multiple components and targets is easy to combine with 3CLpro and ACE2, and exerts an anti-COVID-19 pneumonia effect through multi-component and multi-target, and plays the role of anti-COVID-19 pneumonia in multi-pathway.

References

  1. National Health Commission of the People’s Republic of China, National Administration of Traditional Chinese Medicine. Diagnosis and treatment plan for pneumonia caused by novel coronavirus infection (3th to 7th ed). Available at http://www.nhc.gov.cn/yzygj/s7653p/new_list.shtml.

  2. Chen JY, Shi JS, Yau TO, Liu C, Li X, Zhao Q, et al. Bioinformatics analysis of the 2019 novel coronavirus genome. Chin J BioI (Chin):1–10[2020-03-13]. Available at http://kns.cnki.net/kcms/detail/23.1513.q.20200120.0839.002.html.

    Google Scholar 

  3. Xu XT, Chen P, Wang JF, Feng JN, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China (Life Sci) 2020;63:457–460.

    CAS  Article  Google Scholar 

  4. Zong Y, Ding ML, J KK, Ma ST, Ju WZ. Exploring active compounds of Da-Yuan-Yin in treatment of COVID-19 based on network pharmacology and molecular docking method. Chin Tradit Herb Drugs (Chin) 2020;51:836–844.

    Google Scholar 

  5. Wang W, Wang YW, Ma S, Li RF. Analysis on strategy, participation rate and cure effect of traditional Chinese medicine in treating COVID-19 in 23 provinces (Municipalities and Autonomous Regions). World J Tradit Chin Med (Chin) 2020;15:813–818.

    Google Scholar 

  6. Hirayama N. Docking simulations between drugs and HLA molecules associated with idiosyncratic drug toxicity. Drug Metab Pharmacokinet 2017;32:31–39.

    CAS  Article  Google Scholar 

  7. Li J, Zhao P, Li Y, Tian Y, Wang Y. Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease. Sci Rep 2015;5:15290.

    CAS  Article  Google Scholar 

  8. Yu MK, Chai QY, Liang CH, Ding YQ, Lin ZY, Gao JQ, et al. An analyze of the traditional Chinese medicine prevention and treatment interventions for COVID-19. Chin Tradit Herb Drugs (Chin) 2020;61:383–387.

    Google Scholar 

  9. Ran J, Li YP, Li QT, Liu HB, Zeng CF, Ren Y, et al. Study of TCM syndrome in 209 novel coronavirus pneumonia cases of Chongqing in 2020. J Emerg Tradit Chin Med (Chin):1–3[2020-03-13]. Available at http://kns.cnki.net/kcms/detail/50.1102.R.20200305.1611.002.html.

    Google Scholar 

  10. Duan HY, Ma C. Experimental study on pyretolysis mechanism of compatible application of Japanese Honeysuckle Flower Bud and Weeping Forsythia Fruit. J Modern J Integr Tradit Chin West Med (Chin) 2009;18:1214–1216.

    Google Scholar 

  11. Ding XY, Lin ZJ, Wang D. Research progress on constituents and pharmacological actions of Lonicerae Japonicae Flos, Forsythiae Fructus and their combination. Shandong Sci (Chin) 2019;32:36–41.

    Google Scholar 

  12. Liang JJ, LV J, Lu LR. The regulation and function of TCR signaling pathway. Chin Bull Life Sci (Chin) 2016;28:153–161.

    Google Scholar 

  13. Cui XY. The antiinflammatory and immunomodulation effects of the extract of Louicera Japonica Thunb. Chin Pharm (Chin) 2011;20:8–9.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All authors participated in the review of the manuscript. Gao LQ, Xu J and Chen SD analyzed data and wrote the manuscript.

Corresponding author

Correspondence to Shao-dong Chen.

Ethics declarations

The authors declare that they have no conflict of interests.

Additional information

Supported by the Fundamental Research Funds for the Central Central University, Scientific Research Project on Prevention and Treatment Emergency in Novel Coronavirus (No.20720200034)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gao, Lq., Xu, J. & Chen, Sd. In Silico Screening of Potential Chinese Herbal Medicine Against COVID-19 by Targeting SARS-CoV-2 3CLpro and Angiotensin Converting Enzyme II Using Molecular Docking. Chin. J. Integr. Med. 26, 527–532 (2020). https://doi.org/10.1007/s11655-020-3476-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-020-3476-x

Keywords

  • molecular docking
  • COVID-19
  • SARS-CoV-2 3CL hydrolytic enzyme
  • angiotensin converting enzyme II
  • Chinese medicine