Glycyrrhizin Effectively Inhibits SARS-CoV-2 Replication by Inhibiting the Viral Main Protease

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2021 Apr 30

PMID 33918301

Citations 83

Authors

Lukas van de Sand

Maren Bormann

Mira Alt

Leonie Schipper

Christiane Silke Heilingloh

Eike Steinmann

Daniel Todt

Ulf Dittmer

Carina Elsner

Oliver Witzke

Adalbert Krawczyk

Affiliations

Soon will be listed here.

Abstract

The outbreak of SARS-CoV-2 developed into a global pandemic affecting millions of people worldwide. Despite one year of intensive research, the current treatment options for SARS-CoV-2 infected people are still limited. Clearly, novel antiviral compounds for the treatment of SARS-CoV-2 infected patients are still urgently needed. Complementary medicine is used along with standard medical treatment and accessible to a vast majority of people worldwide. Natural products with antiviral activity may contribute to improve the overall condition of SARS-CoV-2 infected individuals. In the present study, we investigated the antiviral activity of glycyrrhizin, the primary active ingredient of the licorice root, against SARS-CoV-2. We demonstrated that glycyrrhizin potently inhibits SARS-CoV-2 replication in vitro. Furthermore, we uncovered the underlying mechanism and showed that glycyrrhizin blocks the viral replication by inhibiting the viral main protease M that is essential for viral replication. Our data indicate that the consumption of glycyrrhizin-containing products such as licorice root tea of black licorice may be of great benefit for SARS-CoV-2 infected people. Furthermore, glycyrrhizin is a good candidate for further investigation for clinical use to treat COVID-19 patients.

Citing Articles

Anatolian medicinal plants as potential antiviral agents: bridging traditional knowledge and modern science in the fight against COVID-19 and related viral infections.

Tilkat E, Jahan I, Hoser A, Kaplan A, Ozdemir O, Onay A Turk J Biol. 2024; 48(4):218-241.

PMID: 39296335 PMC: 11407354. DOI: 10.55730/1300-0152.2699.

Optimization of indole acetic acid produced by plant growth promoting fungus, aided by response surface methodology.

Arora P, Tabssum R, Gupta A, Kumar S, Gupta S Heliyon. 2024; 10(14):e34356.

PMID: 39108881 PMC: 11301350. DOI: 10.1016/j.heliyon.2024.e34356.

Efficacy and safety of a novel antiviral herbal preparation in ICU-admitted patients with COVID-19: A phase III double-blinded controlled trial.

Avicenna J Phytomed. 2024; 14(2):215-228.

PMID: 38966633 PMC: 11221769. DOI: 10.22038/AJP.2023.23259.

The efficacy of herbal medicines on the length of stay and negative conversion time/rate outcomes in patients with COVID-19: a systematic review.

Latarissa I, Meiliana A, Sormin I, Sugiono E, Wathoni N, Barliana M Front Pharmacol. 2024; 15:1383359.

PMID: 38873430 PMC: 11169809. DOI: 10.3389/fphar.2024.1383359.

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning.

Juarez-Mercado K, Gomez-Hernandez M, Salinas-Trujano J, Cordova-Bahena L, Espitia C, Perez-Tapia S Pharmaceuticals (Basel). 2024; 17(2).

PMID: 38399455 PMC: 10892746. DOI: 10.3390/ph17020240.

References

Kwon Y, Son D, Chung T, Lee Y . A Review of the Pharmacological Efficacy and Safety of Licorice Root from Corroborative Clinical Trial Findings. J Med Food. 2019; 23(1):12-20. DOI: 10.1089/jmf.2019.4459. View

Srivastava V, Yadav A, Sarkar P . Molecular docking and ADMET study of bioactive compounds of against main protease of SARS-CoV2. Mater Today Proc. 2020; 49:2999-3007. PMC: 7556787. DOI: 10.1016/j.matpr.2020.10.055. View

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M . Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3):269-271. PMC: 7054408. DOI: 10.1038/s41422-020-0282-0. View

Yamamura Y, Kawakami J, Santa T, Kotaki H, Uchino K, Sawada Y . Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high-performance liquid chromatographic method. J Pharm Sci. 1992; 81(10):1042-6. DOI: 10.1002/jps.2600811018. View

Zhang L, Wang B . Randomized clinical trial with two doses (100 and 40 ml) of Stronger Neo-Minophagen C in Chinese patients with chronic hepatitis B. Hepatol Res. 2002; 24(3):220. DOI: 10.1016/s1386-6346(02)00086-4. View

Huang W, Chen X, Li Q, Li P, Zhao G, Xu M . Inhibition of intercellular adhesion in herpex simplex virus infection by glycyrrhizin. Cell Biochem Biophys. 2011; 62(1):137-40. DOI: 10.1007/s12013-011-9271-8. View

van Rossum T, Vulto A, Hop W, Schalm S . Pharmacokinetics of intravenous glycyrrhizin after single and multiple doses in patients with chronic hepatitis C infection. Clin Ther. 2000; 21(12):2080-90. DOI: 10.1016/s0149-2918(00)87239-2. View

Edelman E, Butala N, Avery L, Lundquist A, Dighe A . Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest. N Engl J Med. 2020; 383(13):1263-1275. PMC: 8568064. DOI: 10.1056/NEJMcpc2002420. View

Luyckx V . Nephrotoxicity of alternative medicine practice. Adv Chronic Kidney Dis. 2012; 19(3):129-41. DOI: 10.1053/j.ackd.2012.04.005. View

10.

Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr H . Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003; 361(9374):2045-6. PMC: 7112442. DOI: 10.1016/s0140-6736(03)13615-x. View

11.

Lutter A, Scholka J, Richter H, Anderer U . Applying XTT, WST-1, and WST-8 to human chondrocytes: A comparison of membrane-impermeable tetrazolium salts in 2D and 3D cultures. Clin Hemorheol Microcirc. 2017; 67(3-4):327-342. DOI: 10.3233/CH-179213. View

12.

Narkhede R, Pise A, Cheke R, Shinde S . Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences. Nat Prod Bioprospect. 2020; 10(5):297-306. PMC: 7299459. DOI: 10.1007/s13659-020-00253-1. View

13.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View

14.

Tsai T, Liao J, Shum A, Chen C . Pharmacokinetics of glycyrrhizin after intravenous administration to rats. J Pharm Sci. 1992; 81(9):961-3. DOI: 10.1002/jps.2600810925. View

15.

Toptan T, Hoehl S, Westhaus S, Bojkova D, Berger A, Rotter B . Optimized qRT-PCR Approach for the Detection of Intra- and Extra-Cellular SARS-CoV-2 RNAs. Int J Mol Sci. 2020; 21(12). PMC: 7352576. DOI: 10.3390/ijms21124396. View

16.

Silke Heilingloh C, Aufderhorst U, Schipper L, Dittmer U, Witzke O, Yang D . Susceptibility of SARS-CoV-2 to UV irradiation. Am J Infect Control. 2020; 48(10):1273-1275. PMC: 7402275. DOI: 10.1016/j.ajic.2020.07.031. View

17.

Chrzanowski J, Chrzanowska A, Grabon W . Glycyrrhizin: An old weapon against a novel coronavirus. Phytother Res. 2020; 35(2):629-636. DOI: 10.1002/ptr.6852. View

18.

van Gelderen C, Bijlsma J, van Dokkum W, Savelkoul T . Glycyrrhizic acid: the assessment of a no effect level. Hum Exp Toxicol. 2000; 19(8):434-9. DOI: 10.1191/096032700682694251. View

19.

Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L . Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020; 368(6489):409-412. PMC: 7164518. DOI: 10.1126/science.abb3405. View

20.

Morse J, Lalonde T, Xu S, Liu W . Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV. Chembiochem. 2020; 21(5):730-738. PMC: 7162020. DOI: 10.1002/cbic.202000047. View