Zapping the Common Cold

Viral infections, from flu to hepatitis, have long been considered untreatable. But that's about to change.

In 1918, the writer Mary McCarthy, then just six years old, boarded a train in Seattle, bound for Minneapolis— and orphanhood. Her parents contracted influenza on the train, and a day after they arrived in Minneapolis her mother died. Her father followed the next day. The flu killed at least 20 million people that year, more than 1 percent of the world's population, more than even AIDS has killed.

Influenza still claims more than 20,000 lives in the U.S. each year, but it's only one of many fearsome viruses. HIV and hepatitis B and C cause hundreds of thousands of deaths worldwide, and viruses have been linked to several cancers. Even the virus that causes the common cold can kill infants and the elderly. And hanta and Ebola suggest that new and horrible microbes will arise in the future. This is particularly frightening because, unlike bacterial infections, medicine has never cured a viral illness.

That may be about to change. Last year, Elizabeth Zolowicz and her daughter Jacqueline got the flu. "Both of us were lying in bed with really high fevers, 103 or 104," Elizabeth recalls. "My son turned on the TV, and there was a little blurb about a study being done for a flu medication. So I called."

Elizabeth and her daughter had been sick for a day and a half when they took the experimental drug, called a neuraminidase inhibitor, made by pharmaceutical giant Glaxo Wellcome. "Twenty-four hours later, or even less, we were up and walking around," Elizabeth recalls. Their fevers plummeted, their appetites returned, and their energy rebounded. "It's a great drug with no side effects," says Elizabeth, who usually reacts badly to medicine. "I want to see it on the market quick."

In fact, Relenza, as the drug is called, will probably be in pharmacies in time for next year's flu season. Glaxo applied for approval by the Food and Drug Administration last month, and the drug is expected to sail through. It cut the duration and severity of the illness by about a third, with hardly more side effects than a placebo. Moreover, test-tube studies show the drug is active against all known strains of influenza— including the mysterious avian flu that arose in Hong Kong last year.

What countless mothers have told their children— that there's nothing to be done for a viral illness except to rest and drink lots of fluids— is becoming obsolete. The massive research effort against HIV has resulted in 14 approved drugs that target the AIDS virus, slashing death rates in the developed world. But the lay public thinks of HIV as a special case: The powerful protease inhibitors that turned the tide against AIDS were featured on the cover of Newsweek, lavishly photographed like celebrities. But

the only thing special about them is that they paved the way for other antiviral drugs. Indeed, a new protease inhibitor is about to enter human trials, but it doesn't target HIV. It works against the cold virus. That's right, there's a protease inhibitor being developed for the common cold.

Welcome to the age of antivirals. Glaxo's flu drug is being followed by a similar compound marketed by Roche Labs, and a small company called ViroPharma is expected to win approval within a year for a highly regarded drug that targets enterovirus (the cause of summer flu), ear infections, and viral meningitis, a nasty illness that leads to excruciating, two-week headaches. This drug, called Pleconaril, also appears highly potent against some strains of polio and against almost all variants of rhinovirus, the cause of most colds. Farther back in the pipeline are still other medicines that look promising against rhinovirus, as well as hepatitis B and C, Epstein-Barr, CMV, and even Ebola. Back in 1990, only six drugs targeting viruses other than HIV were in human trials, according to the Pharmaceutical Research and Manufacturers of America. By 1996 there were 25, and this year there were 31.

Impressive as those numbers are, they only hint at the potential. Far more auspicious is that there are now tried-and-true strategies for targeting almost any virus. These strategies aren't easy— nothing in biology ever is— and there are limitations, such as drug resistance and the tough, wily nature of some viruses, such as HIV, that may never be cured, only held in check. Still, says Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), "as we enter the new millennum, it's going to be a great era for the development of antiviral drugs."

Such optimism was echoed by more than a dozen researchers in government, academia, and industry. "When I was a medical student in the late '60s and early '70s," says Stephen Straus, a leading virologist at NIAID, "the people interested in studying antiviral drugs were involved in such esoteric, out-of-the-way, unpromising niches that no one thought their work would amount to anything." As it turned out, the effort to cure viral illnesss has shed new light on many fundamental areas of biology, thus contributing far beyond the harvest of new treatments.

Viruses, which consist of only a few genes sheathed in protein, exist in a twilight zone between the animate and the inanimate. By themselves they are inert, unable to replicate. But inside a cell they become energetic parasites, exploiting the host's chemicals to churn out copies of themselves. Viruses are so dependent on cells, explains Catherine Laughlin, a top virologist at NIAID, that "for a long time the dogma was that antivirals weren't possible, because anything that kills the virus also kills the cell."

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