Glycyrrhizin was valued in ancient Arabia and Greece for treating coughs and in China for relieving irritation of the mucous membranes. In modern times, glycyrrhizin has been shown to be a formidable antiviral, fighting herpes, HIV, hepatitis, influenza, encephalitis and pneumonia as well as less known viruses like respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus.
Glycyrrhizin Has Medicinal Properties
You may think of licorice as an extract, a sweetener or even a candy, like Good and Plenty, but it’s actually complex biochemically and offers important medical benefits. According to PubChem, a database of chemical molecules maintained by the National Center for Biotechnology Information,
“Glycyrrhizic acid is extracted from the root of the licorice plant; Glycyrrhiza glabra. It is a triterpene glycoside with glycyrrhetinic acid that possesses a wide range of pharmacological and biological activities … potential immunomodulating, anti-inflammatory, hepato- and neuro-protective, and antineoplastic activities.
Glycyrrhizin modulates certain enzymes involved in inflammation and oxidative stress, and downregulates certain pro-inflammatory mediators, thereby protecting against inflammation- and reactive oxygen species (ROS)-induced damage. Glycerrhizin may also suppress the growth of susceptible tumor cells.”
According to Botanical Medicine, the anti-inflammatory actions of glycyrrhizin (GL) may stem from suppression of cytokines:
“As testimony to its anti-inflammatory properties, glycyrrhizin alleviated allergic asthma in an experimental mouse model, increased the IL-4 and IL-5 levels, decreased eosinophil counts and IgE levels, and upregulated total IgG2a in serum.
These results indicated that glycyrrhizin interfered with the production of IgE by decreasing the IgE-stimulating cytokines. It also attenuated lung inflammation and mucus production in mice.”
Glycyrrhizin and SARS
Early SARS-CoV-1 patients were given the viral compound ribavirin, but it showed little benefit. Corticosteroids were also tried in SARS-CoV-1 patients and patients with MERS (Middle East Respiratory Syndrome), which occurred 10 years later, but there was “no evidence showing that the mortality of SARS-CoV-1 and MERS patients was reduced,” as reported in the International Journal of Biological Sciences.
Soon after the SARS-CoV-1 outbreak, the medical journal The Lancet published a research letter suggesting that glycyrrhizin might fight SARS:
“The outbreak of SARS warrants the search for antiviral compounds to treat the disease. At present, no specific treatment has been identified for SARS-associated coronavirus infection. We assessed the antiviral potential of ribavirin, 6-azauridine, pyrazofurin, mycophenolic acid, and glycyrrhizin against two clinical isolates of coronavirus from patients with SARS …
Of all the compounds, glycyrrhizin was the most active in inhibiting replication of the SARS-associated virus. Our findings suggest that glycyrrhizin should be assessed for treatment of SARS.”
Glycyrrhizin had several positive actions, wrote the researchers:
“In addition to inhibition of virus replication, glycyrrhizin inhibits adsorption and penetration of the virus — early steps of the replicative cycle … Glycyrrhizin was most effective when given both during and after the adsorption period …
… glycyrrhizin and its aglycone metabolite 18β glycyrrhetinic acid upregulate expression of inducible nitrous oxide synthase and production of nitrous oxide in macrophages.
Nitrous oxide inhibits replication of several viruses — eg, Japanese encephalitis virus, which can also be inhibited by glycyrrhizin. Our preliminary results show that glycyrrhizin induces nitrous oxide synthase in Vero cells [cells used in cultures] and that virus replication is inhibited when the nitrous oxide donor is added to the culture medium.”
Glycyrrhizin May Act Differently From Other Substances
According to the Journal of General Virology, glycyrrhizin’s method of stopping the replication of SARS viruses may differ from other treatments that have been tried:
“Unlike IFN-α and ribavirin, there are few clues to the antiviral mechanism of glycyrrhizin. Our data indicate that, as for ribavirin, glycyrrhizin only moderately affects coronavirus replicase functions.
However, in contrast to ribavirin, glycyrrhizin has been shown to inhibit SARS-CoV replication in tissue culture. This indicates that glycyrrhizin may not target the coronavirus replication machinery and that antiviral effects may be exerted, for example, during virus adsorption or release.”
Stopping replication is especially challenging because of the peculiarities of the SARS virus. According to General Cell Biology & Physiology:
“These analyses revealed that SARS-CoV-2 reshapes central cellular pathways, such as translation, splicing, carbon metabolism and nucleic acid metabolism. Small molecule inhibitors targeting these pathways were tested in cellular infection assays and prevented viral replication.”
Glycyrrhizin’s upregulation of nitric oxide and nitric oxide synthase in macrophages, which was noted in the International Journal of Infectious Diseases, may explain its ability to stop replication of SARS and hopefully other coronaviruses like SARS-CoV-2.