Antiviral Potency of Glycyrrhizin and Glycyrrhetic Acid against SARS-CoV-2 Infection of the Non-Structural Protein 3, Main Protease, and Spike Glycoprotein Receptors
Abstract
The efforts to develop antiviral for Covid-19 are still being conducted. One of them is the exploration of the antiviral potency of the compounds found in licorice namely glycyrrhizin and glycyrrhetic acid. They are used and developed further using molecular docking. The research aims to predict the antiviral potency of glycyrrhizin and glycyrrhetic acid against SARS-CoV 2 infection. The researcher employs SwissADME Tool in testing Lipinski’s rule of five fulfillments to predict their physicochemistry. To get an optimum result, the researcher prepares the compounds and receptors. The receptors are validated with RMSD value <2Å, namely Non-Structural Protein 3 (6VXS), Main Protease (6W63), and Spike Glycoprotein (6VSB). The result shows that glycyrrhetic acid fulfills Lipinski’s rule of five, in contrast with glycyrrhizin. Both compounds have good energy affinity and inhibition constant with the best value -13.6 kcal/mol and 0.000104 µM on the receptor 6W63. The interaction between Glycyrrhizin and amino acid residue is found in the interaction with the 6VXS, 6W63, and 6VSB receptors. Meanwhile, glycyrrhetic acid compound only interacts with the receptor 6VXS. The interaction between glycyrrhizin and glycyrrhetic acid and its target protein has antiviral activity potency against SARS-CoV 2 infection.
References
Ajay Kumar, T. V., Kabilan, S., & Parthasarathy, V. (2017). Screening and Toxicity Risk Assessment of Selected Compounds to Target Cancer using QSAR and Pharmacophore Modelling. International Journal of PharmTech Research, 10(4), 219–224. https://doi.org/10.20902/ijptr.2017.10428
Banerjee, P., Eckert, A. O., Schrey, A. K., & Preissner, R. (2018). ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(W1), W257–W263. https://doi.org/10.1093/nar/gky318
Chemistry, O. (2010). ACS Paragon Plus Environment. Interface, 5(2), 1–23. http://www.ncbi.nlm.nih.gov/pubmed/20030414
Chitranshi, N., Gupta, V. K., Rajput, R., Godinez, A., Pushpitha, K., Shen, T., Mirzaei, M., You, Y., Basavarajappa, D., Gupta, V., & Graham, S. L. (2020). Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLprotargeting repurposed drug candidates. Journal of Translational Medicine, 18(1), 1–15. https://doi.org/10.1186/s12967-020-02448-z
Choudhary, S., Malik, Y. S., & Tomar, S. (2020). Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. Frontiers in Immunology, 11(July). https://doi.org/10.3389/fimmu.2020.01664
Fiorucci, D., Milletti, E., Orofino, F., Brizzi, A., Mugnaini, C., & Corelli, F. (2020). Computational drug repurposing for the identification of SARS-CoV-2 main protease inhibitors. Journal of Biomolecular Structure and Dynamics, 0(0), 1–7. https://doi.org/10.1080/07391102.2020.1796805
Gaba Monika, Gaba Punam1, Singh Sarbjot, and G. G. (2010). An Overview Of Molecular Docking. Discovery, 2(2), 219–231.
Gurung, A. B., Bhattacharjee, A., & Ali, M. A. (2016). Exploring the physicochemical profile and the binding patterns of selected novel anticancer Himalayan plant derived active compounds with macromolecular targets. Informatics in Medicine Unlocked, 5(September), 1–14. https://doi.org/10.1016/j.imu.2016.09.004
Hevener. (2005). Public validation of Molecular Docking Programs For Virtual Screening Against Dihydropteroate Synthase J. Chem Inf Model, 23(1), 1–7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf
Kumar, S., Kaur, R., Rajput, R., & Singh, M. (2018). Bio pharmaceutics classification system (BCS) class IV drug nanoparticles: Quantum leap to improve their therapeutic index. Advanced Pharmaceutical Bulletin, 8(4), 617–625. https://doi.org/10.15171/apb.2018.070
Leong, M. K., Syu, R. G., Ding, Y. L., & Weng, C. F. (2017). Prediction of N-Methyl-D-Aspartate Receptor GluN1-Ligand Binding Affinity by a Novel SVM-Pose/SVM-Score Combinatorial Ensemble Docking Scheme. Scientific Reports, 7(August 2016), 1–15. https://doi.org/10.1038/srep40053
Li, D., Luan, J., & Zhang, L. (2021). Molecular docking of potential SARS-CoV-2 papain-like protease inhibitors. Biochemical and Biophysical Research Communications, 538, 72–79. https://doi.org/10.1016/j.bbrc.2020.11.083
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 64(SUPPL.), 4–17. https://doi.org/10.1016/j.addr.2012.09.019
Markovic, M., Zur, M., Ragatsky, I., Cvijić, S., & Dahan, A. (2020). Bcs class iv oral drugs and absorption windows: Regional-dependent intestinal permeability of furosemide. Pharmaceutics, 12(12), 1–16. https://doi.org/10.3390/pharmaceutics12121175
Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011).\ , 7(2), 146-157. (2011). Molecular docking: a powerful approach for structure-based drug discovery. Current computer-aided drug design. Current Computer Aided Drug Design, 7(2), 146–157. https://www.ingentaconnect.com/content/ben/cad/2011/00000007/00000002/art00008%0Ahttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf
Michalska, K., Kim, Y., Jedrzejczak, R., Maltseva, N. I., Stols, L., Endres, M., & Joachimiak, A. (2020). Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: From the apo form to ligand complexes. IUCrJ, 7(Pt 5), 814–824. https://doi.org/10.1107/S2052252520009653
Mousavizadeh, L., & Ghasemi, S. (2020). Genotype and phenotype of COVID-19: Their roles in pathogenesis. Journal of Microbiology, Immunology and Infection, xxxx, 0–4. https://doi.org/10.1016/j.jmii.2020.03.022
Ortiz, C. L. D., Completo, G. C., Nacario, R. C., & Nellas, R. B. (2019). Potential Inhibitors of Galactofuranosyltransferase 2 (GlfT2): Molecular Docking, 3D-QSAR, and In Silico ADMETox Studies. Scientific Reports, 9(1), 1–28. https://doi.org/10.1038/s41598-019-52764-8
Pantsar, T., & Poso, A. (2018). Binding affinity via docking: Fact and fiction. Molecules, 23(8), 1DUMMY. https://doi.org/10.3390/molecules23081899
Qi, F., Qian, S., Zhang, S., & Zhang, Z. (2020). Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochemical and Biophysical Research Communications, 526(1), 135–140. https://doi.org/10.1016/j.bbrc.2020.03.044
Ramírez, D., & Caballero, J. (2018). Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data? Molecules, 23(5), 1–17. https://doi.org/10.3390/molecules23051038
Shin, D., Mukherjee, R., Grewe, D., Bojkova, D., Baek, K., Bhattacharya, A., Schulz, L., Widera, M., Mehdipour, A. R., Tascher, G., Geurink, P. P., Wilhelm, A., van der Heden van Noort, G. J., Ovaa, H., Müller, S., Knobeloch, K. P., Rajalingam, K., Schulman, B. A., Cinatl, J., … Dikic, I. (2020). Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature, 587(7835), 657–662. https://doi.org/10.1038/s41586-020-2601-5
Wang, L., Yang, R., Yuan, B., Liu, Y., & Liu, C. (2015). The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharmaceutica Sinica B, 5(4), 310–315. https://doi.org/10.1016/j.apsb.2015.05.005
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & Mclellan, J. S. (2019). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. http://science.sciencemag.org/
Zhang, J.-J., Shen, X., Yan, Y.-M., WANG, Y., & Cheng, Y.-X. (2020). Discovery of anti-SARS-CoV-2 agents from commercially available flavor via docking screening. 1–27. https://doi.org/10.31219/osf.io/vjch2
Banerjee, P., Eckert, A. O., Schrey, A. K., & Preissner, R. (2018). ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Research, 46(W1), W257–W263. https://doi.org/10.1093/nar/gky318
Chemistry, O. (2010). ACS Paragon Plus Environment. Interface, 5(2), 1–23. http://www.ncbi.nlm.nih.gov/pubmed/20030414
Chitranshi, N., Gupta, V. K., Rajput, R., Godinez, A., Pushpitha, K., Shen, T., Mirzaei, M., You, Y., Basavarajappa, D., Gupta, V., & Graham, S. L. (2020). Evolving geographic diversity in SARS-CoV2 and in silico analysis of replicating enzyme 3CLprotargeting repurposed drug candidates. Journal of Translational Medicine, 18(1), 1–15. https://doi.org/10.1186/s12967-020-02448-z
Choudhary, S., Malik, Y. S., & Tomar, S. (2020). Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. Frontiers in Immunology, 11(July). https://doi.org/10.3389/fimmu.2020.01664
Fiorucci, D., Milletti, E., Orofino, F., Brizzi, A., Mugnaini, C., & Corelli, F. (2020). Computational drug repurposing for the identification of SARS-CoV-2 main protease inhibitors. Journal of Biomolecular Structure and Dynamics, 0(0), 1–7. https://doi.org/10.1080/07391102.2020.1796805
Gaba Monika, Gaba Punam1, Singh Sarbjot, and G. G. (2010). An Overview Of Molecular Docking. Discovery, 2(2), 219–231.
Gurung, A. B., Bhattacharjee, A., & Ali, M. A. (2016). Exploring the physicochemical profile and the binding patterns of selected novel anticancer Himalayan plant derived active compounds with macromolecular targets. Informatics in Medicine Unlocked, 5(September), 1–14. https://doi.org/10.1016/j.imu.2016.09.004
Hevener. (2005). Public validation of Molecular Docking Programs For Virtual Screening Against Dihydropteroate Synthase J. Chem Inf Model, 23(1), 1–7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf
Kumar, S., Kaur, R., Rajput, R., & Singh, M. (2018). Bio pharmaceutics classification system (BCS) class IV drug nanoparticles: Quantum leap to improve their therapeutic index. Advanced Pharmaceutical Bulletin, 8(4), 617–625. https://doi.org/10.15171/apb.2018.070
Leong, M. K., Syu, R. G., Ding, Y. L., & Weng, C. F. (2017). Prediction of N-Methyl-D-Aspartate Receptor GluN1-Ligand Binding Affinity by a Novel SVM-Pose/SVM-Score Combinatorial Ensemble Docking Scheme. Scientific Reports, 7(August 2016), 1–15. https://doi.org/10.1038/srep40053
Li, D., Luan, J., & Zhang, L. (2021). Molecular docking of potential SARS-CoV-2 papain-like protease inhibitors. Biochemical and Biophysical Research Communications, 538, 72–79. https://doi.org/10.1016/j.bbrc.2020.11.083
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 64(SUPPL.), 4–17. https://doi.org/10.1016/j.addr.2012.09.019
Markovic, M., Zur, M., Ragatsky, I., Cvijić, S., & Dahan, A. (2020). Bcs class iv oral drugs and absorption windows: Regional-dependent intestinal permeability of furosemide. Pharmaceutics, 12(12), 1–16. https://doi.org/10.3390/pharmaceutics12121175
Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011).\ , 7(2), 146-157. (2011). Molecular docking: a powerful approach for structure-based drug discovery. Current computer-aided drug design. Current Computer Aided Drug Design, 7(2), 146–157. https://www.ingentaconnect.com/content/ben/cad/2011/00000007/00000002/art00008%0Ahttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624763/pdf/nihms412728.pdf
Michalska, K., Kim, Y., Jedrzejczak, R., Maltseva, N. I., Stols, L., Endres, M., & Joachimiak, A. (2020). Crystal structures of SARS-CoV-2 ADP-ribose phosphatase: From the apo form to ligand complexes. IUCrJ, 7(Pt 5), 814–824. https://doi.org/10.1107/S2052252520009653
Mousavizadeh, L., & Ghasemi, S. (2020). Genotype and phenotype of COVID-19: Their roles in pathogenesis. Journal of Microbiology, Immunology and Infection, xxxx, 0–4. https://doi.org/10.1016/j.jmii.2020.03.022
Ortiz, C. L. D., Completo, G. C., Nacario, R. C., & Nellas, R. B. (2019). Potential Inhibitors of Galactofuranosyltransferase 2 (GlfT2): Molecular Docking, 3D-QSAR, and In Silico ADMETox Studies. Scientific Reports, 9(1), 1–28. https://doi.org/10.1038/s41598-019-52764-8
Pantsar, T., & Poso, A. (2018). Binding affinity via docking: Fact and fiction. Molecules, 23(8), 1DUMMY. https://doi.org/10.3390/molecules23081899
Qi, F., Qian, S., Zhang, S., & Zhang, Z. (2020). Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochemical and Biophysical Research Communications, 526(1), 135–140. https://doi.org/10.1016/j.bbrc.2020.03.044
Ramírez, D., & Caballero, J. (2018). Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data? Molecules, 23(5), 1–17. https://doi.org/10.3390/molecules23051038
Shin, D., Mukherjee, R., Grewe, D., Bojkova, D., Baek, K., Bhattacharya, A., Schulz, L., Widera, M., Mehdipour, A. R., Tascher, G., Geurink, P. P., Wilhelm, A., van der Heden van Noort, G. J., Ovaa, H., Müller, S., Knobeloch, K. P., Rajalingam, K., Schulman, B. A., Cinatl, J., … Dikic, I. (2020). Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature, 587(7835), 657–662. https://doi.org/10.1038/s41586-020-2601-5
Wang, L., Yang, R., Yuan, B., Liu, Y., & Liu, C. (2015). The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharmaceutica Sinica B, 5(4), 310–315. https://doi.org/10.1016/j.apsb.2015.05.005
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & Mclellan, J. S. (2019). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. http://science.sciencemag.org/
Zhang, J.-J., Shen, X., Yan, Y.-M., WANG, Y., & Cheng, Y.-X. (2020). Discovery of anti-SARS-CoV-2 agents from commercially available flavor via docking screening. 1–27. https://doi.org/10.31219/osf.io/vjch2
Published
2025-03-25
How to Cite
MUTIAH, Roihatul et al.
Antiviral Potency of Glycyrrhizin and Glycyrrhetic Acid against SARS-CoV-2 Infection of the Non-Structural Protein 3, Main Protease, and Spike Glycoprotein Receptors.
Proceedings of International Pharmacy Ulul Albab Conference and Seminar (PLANAR), [S.l.], v. 4, p. 44-53, mar. 2025.
ISSN 2827-7848.
Available at: <https://conferences.uin-malang.ac.id/index.php/planar/article/view/3313>. Date accessed: 05 feb. 2026.
doi: https://doi.org/10.18860/planar.v4i0.3313.
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