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Sweet Treatment for SARS

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Since severe acute respiratory syndrome–or SARS–burst on the scene this past March, physicians have reported more than 8,400 cases worldwide. The flulike lung disease appears to have emerged in mainland China, where officials have acknowledged 7,083 cases so far.

Within weeks of the initial announcement of this new disease by the U.S. Centers for Disease Control and Prevention, SARS victims were being diagnosed in some 30 countries. To date, roughly one in 10 infected people has died, although most of those lethal infections have occurred in Asia. In the United States, all 175 people with possible SARS and 35 with probable SARS have recovered.

What has made SARS' emergence so scary is its rapid global spread and the lack of effective drugs to treat the viral infection. Right now, virologists are hard at work to develop vaccines that might be tested as early as this coming winter, when SARS infections are expected to break out again.

However, a team of scientists in Germany has stumbled upon a promising drug that, at least in the test tube, not only fights the SARS virus, but also lessens the inflammatory symptoms that may underlie the disease's deadliness.

This new wonder drug is actually a flavoring popular in some old-fashioned candies. It's glycyrrhizin, the compound that gives licorice its characteristic taste.

A medicinal alter ego

Candy makers extract glycyrrhizin from the roots of licorice plants (Glycyrrhiza glabra L.). Some 50 times sweeter than table sugar, the substance has been used beyond licorice as an all-natural, low-calorie sweetener for chocolate, beer, and chewing gum.

Herbal-medicine practitioners long ago turned to this compound for treating allergies, arthritis, and a host of other chronic conditions. More recently, science has confirmed the therapeutic power of glycyrrhizin. Japanese researchers, for instance, have experimented with the compound against hepatitis, and other researchers have explored its potential in fighting cancer.

It was against this backdrop that Jindrich Cinatl and his colleagues at the Frankfurt University Medical School decided to test glycyrrhizin against the corona virus that causes SARS. They used viruses isolated from two SARS patients admitted earlier this year to the German University's medical center.

Cinatl's team first filled test tubes with healthy, growing animal cells typically used in studies of viruses. Some cell samples were left alone, and others were infected with the SARS virus. Many of the latter were grown in various concentrations of glycyrrhizin, an antiviral drug, or an anticancer drug.

In the June 14 Lancet, Cinatl's team reports that glycyrrhizin dramatically outperformed the other agents in limiting the virus' infectivity and deadliness to the cells. The licorice extract was more potent than any of the four established drugs tested, and it inhibited reproduction of the SARS virus at doses that were nontoxic to the test cells. Two of the established drugs stopped the SARS virus, but only when they were at concentrations that would be toxic to a person.

The researchers say that glycyrrhizin appears to the spur macrophages to produce nitric oxide, a compound that inhibits the growth of several viruses. Macrophages are housekeeping cells that normally gobble up and destroy cellular trash, including viruses. Cinatl's team also found that glycyrrhizin turned off two enzymes essential to replication of genetic material by the SARS virus. Clearly, Cinatl says, glycyrrhizin has a direct effect on the virus.

But at least as important, he adds, the licorice compound exhibits anti-inflammatory and proimmunity actions independent of any effect on viral growth. Why is that important? With SARS, "you can't correlate tissue damage in the lung with virus [counts]," Cinatl notes. Viruses tend to reach their maximum numbers in patients 5 to 10 days after infection. Ten to 15 days later, viral counts in a patient's blood have subsided, yet that person can be in severe inflammatory distress. Glycyrrhizin holds the prospect of fighting SARS by multiple mechanisms at various stages of the infection, Cinatl told Science News Online.

Not totally benign

Glycyrrhizin is available as an herbal remedy and is regarded as safe for people to take at small doses for long periods. However, Cinatl points out that to get the anti-SARS effects that his tests established in the test tube, a person would have to take large quantities of glycyrrhizin over several weeks.

At a minimum, he says, this would be more than individuals could derive even if they ate huge amounts of licorice candy.

Moreover, some individuals taking high doses of glycyrrhizin will suffer elevated blood pressure or depressed concentrations of potassium in their blood. Indeed, Cinatl cautions that doctors prescribing glycyrrhizin would have to monitor their patients for warnings of toxicity. No one should attempt to self-medicate against SARS with glycyrrhizin.

It's even possible to overdose on licorice candy. Researchers at universities in Padua and Sassari, Italy, administered 7 grams of licorice to men daily for 1 week. Four years ago, the scientists reported In the New England Journal of Medicine that testosterone concentrations in the men's blood plummeted while progesterone–a type of female sex hormone–increased. The good news: Values of each hormone returned to about normal within 4 days of the men laying off the licorice.

The researchers noted that "amounts of licorice given to these men are eaten by many people. Thus, men with decreased libido or other sexual dysfunction, as well as those with hypertension, should be questioned [by their doctors] about licorice ingestion."

Presumably, even temporary sexual side effects would be a welcome tradeoff for people diagnosed with SARS. However, Cinatl stresses, what all such data reinforce is that even natural products, when taken in large amounts, can have druglike impacts. As such, they should be treated with respect and taken in large amounts only under a doctor's supervision.

Which, apparently, is what has already begun in China. Cinatl says he's gotten word that physicians there have launched clinical trials of glycyrrhizin's effect on patients with SARS. To date, he notes, the doctors have yet to report the outcome.

Citations

Jindrich Cinatl

Institute of Medical Virology

Frankfurt University Medical School

Paul-Ehrlich Strasse 40

D-60596 Frankfurt

Germany
Further Reading

Harder, B. 2003. Out of China: SARS virus' genome hints at independent evolution. Science News 163(April 26):262. Available at [Go to].

______. 2003. Morbid mystery tour: Epidemic from China is encircling globe. Science News 163(March 29):198. Available to subscribers at [Go to].

For further information from the World Health Organization concerning the Severe Acute Respiratory Syndrome (SARS), go to [Go to].

For further information from the Centers for Disease Control and Prevention concerning the Severe Acute Respiratory Syndrome (SARS), go to [Go to].

For information from the Memorial Sloan-Kettering Cancer Center on licorice as an herbal medicine, go to [Go to].

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