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While the discovery and development of drugs to treat active herpes infection has increased significantly in recent years, all currently available drugs are ineffective against latent infection.

Therefore, a team of investigators explored whether glycyrrhizic acid, a compound found in licorice and known to have antiviral properties, especially against the herpes virus, could interfere with latent infection of Kaposi sarcoma-associated herpes virus (KSHV) in vitro. The researchers were led by Francesca Curreli of the New York University School of Medicine, and they published details of their work in The Journal of Clinical Investigation.

The researchers treated 12 human cell types, both infected and uninfected, with doses of glycyrrhizic acid (GA) ranging from 0.5 to 6 mM [millimole]. The effect of the glycyrrhizic acid was determined by monitoring cell growth and analyzing gene and protein expression patterns of treated and untreated cells. Treated cells were also compared to another control group of cells given a low dose of ethanol.

Key results included the following:

• At doses of 2 to 4 mM, glycyrrhizic acid dramatically or completely eliminated infected cells in 6 to 16 days with no apparent toxic effect on healthy cells.

• Lower doses of glycyrrhizic acid had little or no effect, and higher doses were toxic for all cell lines.

• Glycyrrhizic acid appeared to decrease expression levels of one viral protein, latency-associated nuclear antigen (LANA), and increase expression levels of another viral protein, v-cyclin. Both proteins help the virus to persist in its latent state.

"Taken together, these results suggest that the presence of KSHV in its latent state makes the cells susceptible to apoptosis when treated with GA and that the change in the expression patterns of LANA and v-cyclin is responsible for the apoptotic affects," the researchers concluded.

In an editorial accompanying the study, Jeffrey I. Cohen, a virologist at the National Institutes of Health, welcomed these findings but noted several obstacles that must be overcome before glycyrrhizic acid could become a viable treatment for latent herpes infection.

Since glycyrrhizic acid administered orally is modified in the digestive tract, its modified form would need to be effective against latent virus infection, Cohen explained. If the modified form were not effective, then glycyrrhizic acid would have to be administered intravenously.

However, intravenous glycyrrhizic acid comes with its own obstacle: Previous experiments have shown that administering it intravenously results in serum levels in the microgram range, much higher than the millimolar concentrations which proved toxic in these experiments. "Therapeutic levels of GA might be toxic for normal cells and tissues," Cohen said.

Chronic ingestion of licorice results in a syndrome similar to that in primary hyperaldosteronism with hypertension, hypokalemia, and metabolic alkalosis. The syndrome is due to inhibition of the enzyme 11ß­hydroxysteroid dehydrogenase in the kidney, which allows cortisol to act as the major endogenous mineralocorticoid.

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