glycyrrhizin in licorice prevents inflammatory cytokine storm of COVID-19 and prevents SARS-COV-2 viral replication

Long before licorice was a candy, licorice root was a herb. Now this herb may be a sweet treatment for COVID.

In China, a herbal combination that includes licorice has led to a positive response in 90% of COVID patients (Chin J Nat Med 2020;18:226–30).

The Research
Licorice first attracted attention nearly two decades ago when the licorice component glycyrrhizin demonstrated an ability in the laboratory to plug the ACE-2 receptors that the SARS-CoV-2 virus uses as a doorway into human cells, where it takes over the cell’s machinery, allowing it to replicate and do its damage (Journal of Virology 2004:11334–11339). Glycyrrhizin, it turned out, was able to inhibit replication of the COVID related SARS virus (Lancet 2003;361(9374):2045-6).

More relevant still, recent studies have found that glycyrrhizin may target the ACE-2 receptor and prevent SARS-CoV-2 entry (Preprints;doi.org/10.20944/preprints202001.0358.v3; Chin Trad Herbal Drug;4(51):845-850,20200228). Other in vitro studies have found glycyrrhizic acid from licorice to be effective against several proteins targeted by the SARS-CoV-2 virus, meaning that licorice could help treat the effects of the virus (Computers in Biology and Medicine 2020,124,103936).

The Newest Study
People whose COVID symptoms become severe often experience a cytokine storm, an exaggerated inflammatory immune response. This out of control inflammatory immune response may be what leads to the acute respiratory distress syndrome and multiple organ failure that comes with severe COVID.

HMGB1 promotes release of proinflammatory cytokines and plays an important role in inflammation. It has been found to be involved in susceptibility to the SARS-COV-2 virus that causes COVID-19. People with severe COVID have been reported to have elevated levels of HMGB1.

Licorice is a powerful antiviral and antiinflammatory herb. Glycyrrhizin, an important active ingredient in licorice, binds to HMGB1 and inhibits its cytokine activity. By binding to HMGB1, it can also inhibit viral replication, perhaps because the SARS-COV-2 virus enters our cells by binding to ACE-2 receptors, and HMGB1 plays a role in regulating ACE-2 expression. Glycyrrhizin has already shown that it can interfere with SARS-associated viruses.

When researchers looked at the effect of glycyrrhizin on COVID-19 in a laboratory study, they discovered two important things. The first is that glycyrrhizin prevents the inflammation and the lung cell death it causes. The second is that it significantly inhibited SARS-COV-2 replication. These two important findings call for further research into licorice as a therapy for COVID-19.


Cytokine June 2021;142:155496


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