COVID-19 Research Paper Volume 13, Issue 4 pp 4811—4830

Chemical composition and pharmacological mechanism of ephedra-glycyrrhiza drug pair against coronavirus disease 2019 (COVID-19)

Xiaoling Li1, *, , Qin Qiu2, *, , Mingyue Li3, *, , Haowen Lin4, , Shilin Cao5,6, , Qu Wang4, , Zishi Chen5, , Wenhao Jiang5, , Wen Zhang7, , Yuge Huang8, , Hui Luo9, , Lianxiang Luo9,10, ,

  • 1 Animal Experiment Center of Guangdong Medical University, Zhanjiang 524023, Guangdong, China
  • 2 Graduate School of Guangdong Medical University, Zhanjiang 524023, Guangdong, China
  • 3 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
  • 4 The First Clinical College of Guangdong Medical University, Zhanjiang 524023, Guangdong, China
  • 5 Group of Sustainable Biochemical Engineering, School of Food Science and Engineering, Foshan University, Foshan 528000, Guangdong, China
  • 6 Sustainable Biochemical and Biosynthetic Engineering Center, Foshan Wu-Yuan Biotechnology Co., Ltd., Guangdong Biomedical Industrial Base, Foshan 528000, Guangdong, China
  • 7 Aditegen LLC, Jersey, NJ 07310, USA
  • 8 Department of Pediatrics, the Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
  • 9 The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, Guangdong, China
  • 10 Marine Medical Research Institute of Zhanjiang, Zhanjiang 524023, Guangdong, China
* Equal contribution

Received: August 26, 2020       Accepted: November 30, 2020       Published: February 13, 2021
How to Cite

Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Traditional Chinese medicine (TCM) had demonstrated effectiveness in the prevention and control of COVID-19. Statistics showed that Ephedra and Glycyrrhiza were frequently used in the treatment of COVID-19. We hypothesized that the Ephedra-Glycyrrhiza drug pair is a potential choice for the treatment of COVID-19. Here, 112 active compounds were identified from Ephedra-Glycyrrhiza via network pharmacology approach. Ephedra-Glycyrrhiza pair enrichment analysis demonstrated that these compounds might participate in the cAMP, PI3K-Akt, JAK-STAT and chemokine signaling pathways, which had a high correlation with respiratory, nervous, blood circulation and digestive system-related diseases. Pathway analysis between Ephedra-Glycyrrhiza and COVID-19 showed that the key targets were TNF-α, IL2, FOS, ALB, and PTGS2. They might control PI3K-Akt signaling pathway to exert immune regulation, organ protection and antiviral effects. Molecular docking results showed that the active compounds from the Ephedra-Glycyrrhiza pair bound well to COVID-19 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). The Molecular dynamics simulation was analyzed for the stability and flexibility of the complex. In conclusion, our study elucidated the potential pharmacological mechanism of Ephedra-Glycyrrhiza in the treatment of COVID-19 through multiple targets and pathways.


COVID-19: Coronavirus Disease 2019; DAVID: Database for Annotation, Visualization and Integrated Discovery; DL: Drug-likeness evaluation; EG: Ephedra-Glycyrrhiza; ETCM: Encyclopedia of Traditional Chinese Medicine; GA: Glycyrrhizic acid; GAD Disease Analysis: Genetic Association Database Disease Analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; MD: molecular dynamics simulations; MERS-CoV: Middle Eastern respiratory syndrome-related coronavirus; Mpro: M hydrolase; NAbs: neutralizing antibody; nsp1-nsp16: 16 non-structural proteins; OB: oral bioavailability; PBC: periodic boundary condition; PDB: protein data bank; SARS-CoV: severe acute respiratory syndrome coronavirus; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; S protein: spike protein; TCM: Traditional Chinese medicine; TCMSP: Traditional Chinese Medicine Systems Pharmacology Database.