EXTON, Pa. -- Certainly a cure for the common cold would be a big story all by itself. But how about a medicine that also stops viral meningitis? The summer flu? Deadly newborn infections? Even polio?
One drug that does all this is surprisingly close. It is called pleconaril, and if large-scale testing turns out well, it could be in drugstores within a year.
Pleconaril (pronounced plah-CONN-ah-rill) is the latest in a short list of medicines that kill viruses. This drug, in fact, blocks an entire category of them, a collection of 169 distinctly different nasties that together cause more human disease than any other.
Almost as remarkable as what pleconaril does, however, is how it came to be. This drug was not so much discovered as designed.
Once drug development was a kind of organized serendipity, screening thousands of random compounds to see what happens. But over the past decade, a quiet series of breakthroughs has transformed the way drugs are developed. Now scientists explore the shape and innards of their target down to the last molecule. Then they fashion chemical monkey wrenches to throw into the works.
Pleconaril is the latest, and one of the most impressive, examples of this new way of creating medicines. It is an exquisitely precise sort of monkey wrench. The drug fits neatly into a groove on the surface of the virus, gumming up the machinery it needs to infect the body's cells.
Experts think the same research techniques will lead to treatments for many other kinds of viruses, predators that are still mostly beyond the powers of modern medicine.
``Pleconaril represents a class of drugs that were designed with the knowledge of the three-dimensional structure of the virus,'' said Dr. Catherine Laughlin, chief of virology at the National Institute of Allergy and Infectious Diseases. ``It provides a lot of hope for the eventual design of drugs for virtually every viral infection.''
Pleconaril is made by ViroPharma Inc., a 5-year-old, 102-employee pharmaceutical firm in the Philadelphia suburbs. The publicly traded company is sponsoring two large studies, due out in the spring, that will determine whether the drug works well enough to win Food and Drug Administration approval.
The company wants to get the drug approved first for viral meningitis, but it is the common cold the most prosaic of infections that is likely to be the medicine's biggest market.
``Everyone talks about the cure for the common cold,'' said Dr. Jose Romero of Creighton University in Nebraska, who has tested the drug on patients. ``This IS the cure for the common cold.''
Attacking viruses
Some might quibble over that word. ``Cure,'' after all, implies that pleconaril will make the sniffles evaporate instantly, which it won't. Still, the medicine can shorten a bad cold by three or four days and help people feel considerably less miserable along the way.
Pleconaril does this by disabling the rhinovirus, the most common human virus.
It also neutralizes the second most common human virus, the enterovirus. Various versions of enteroviruses cause an amazingly broad range of illnesses: lingering summer colds, head-splitting meningitis, childhood fevers, inflammation of the heart, polio, plus overwhelming infections that sometimes kill newborns.
One drug can stop both rhinoviruses and enteroviruses because they are close cousins, members of a large family called picornaviruses.
``There have been a number of anti-picornavirus agents over the last 25 years, but they've had all sorts of problems,'' said Dr. Mark Pallansch, an enterovirus expert at the U.S. Centers for Disease Control and Prevention. ``Pleconaril is the first true, viable product that is potentially licensable.''
ViroPharma estimates that every year, Americans get between 400 million and 500 million picornavirus infections that are serious enough to make them feel bad. It plans to charge between $50 and $100 for enough medicine to cure one infection.
Only one other company appears to be close to ViroPharma for now. Agouron Pharmaceuticals, a part of Warner-Lambert Co., is experimenting this fall on 900 cold victims to see if its nasal spray, code-named AG7088, will speed their recovery.
However, the cold is the least of the reasons why many doctors are so enthusiastic about pleconaril.
Enterovirus infections are occasionally medical emergencies. Over the last two years, the FDA has allowed the company to dispense pleconaril outside organized experiments for infections that are life-threatening or especially gruesome.
So far, nearly 100 people have been treated this way, often with excellent results. For example, the drug has been given to adults with defective immune systems who suffer enterovirus brain infections that simply will not go away. The usual course is inexorably downhill. Doctors say some of these people have fully recovered after a few days of pleconaril.
Doctors have also successfully treated people with myocarditis, an inflammation that can destroy the heart, and with polio, which is also caused by an enterovirus. Overall, doctors estimate about three-quarters of these emergency cases benefited from pleconaril.
Providing proof
Compelling as these cases are, they actually prove little about pleconaril's worth. Even the sickest enterovirus victim may spontaneously recover. For proof, the FDA requires large, carefully designed experiments to compare the medicine with standard care.
ViroPharma hopes first to prove that pleconaril cures viral meningitis, an inflammation of the covering of the brain and spine. The CDC estimates that about 50,000 Americans are hospitalized with it each year, and besides painkillers, there is little doctors can now offer.
So far, small studies on victims of viral meningitis have looked promising, and the results of two large meningitis studies are expected in the spring.
If they turn out as ViroPharma hopes, research director Mark A. McKinlay said the company will seek approval to sell the drug. With a speedy FDA review, this could put a liquid form of pleconaril on the market by the end of 2000.
Next would come a pill, intended for treating colds, that the company hopes to sell in 2001.
