Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation

Abstract

Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19.Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy.Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets.Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

Evaluation of noscapine-licorice combination effects on cough relieving in COVID-19 outpatients: A randomized controlled trial

“…Licorice also has been shown to have antiviral effects against various families, including SARS coronaviruses (Diomede et al, 2021). Moreover, a study using bioinformatics analysis and molecular dynamic stimulation has shown that phaseol in licorice may have beneficial effects in reducing the inflammatory response to COVID-19 by inhibiting the activation of CXCL8 and IL2RA (Cao et al, 2022). An in silico analysis performed by Neeraj kumar et al, showed that the combination of noscapine and hydroxychloroquine conjugates has much binding affinity for main protease of SARS-CoV-2 which has critical role in pathogenesis of COVID-19 (Kumar et al, 2022).…”

“…An in silico analysis performed by Neeraj kumar et al, showed that the combination of noscapine and hydroxychloroquine conjugates has much binding affinity for main protease of SARS-CoV-2 which has critical role in pathogenesis of COVID-19 (Kumar et al, 2022). Other potential effects against COVID-19 symptoms have also been shown for other ingredients of licorice, including Glycerol and Glyasperin F (Cao et al, 2022). Another in vitro study has revealed that licorice may block SARS-CoV-2 replication by inhibiting the viral main protease (van de Sand et al, 2021).…”

Deep learning-based network pharmacology for exploring the mechanism of licorice for the treatment of COVID-19

“…The compound-protein target pair with the highest binding energy of molecular docking was subjected to molecular dynamics (MD) simulations to further check the binding stability of the two. MD simulations were then performed using Gromacs software 36 . To ensure the total charge neutrality of the simulated systems, corresponding amounts of sodium ions were added to the three systems to displace water molecules and produce solvent boxes of appropriate size.…”

Molecular docking and molecular dynamics study Lianhua Qingwen granules (LHQW) treats COVID-19 by inhibiting inflammatory response and regulating cell survival

“…After the energy optimization of the system was completed, the system temperature was steadily increased from 0 K to 298.15 K at a fixed volume and constant ramp rate. The NVT (Isothermal isovolume) system simulation of 500 ps was performed to further uniformly distribute the solvent molecules in the solvent box at the system maintenance temperature of 298.15 K ( Cao et al., 2022c ). Finally, the composite system was subjected to a 100 ns NPT (isothermal isobaric) system simulation.…”