Scientists in search of a SARS cure have narrowed their focus to several dozen drugs that appear to have the best chance of stopping the deadly respiratory virus, but they have abandoned plans to test one of them in people.
The urgent hunt for something that works – preferably a medicine already on the market or close to it – was helped by the breakthrough a week ago in decoding the virus’s genetic makeup, which gives scientists some logical targets.
While they cannot predict when they will find a treatment, they should know soon if an effective medicine is likely to be in hospitals quickly. If none in testing shows promise in the next few weeks, a treatment may have to be created from scratch, a process that could take at least five years.
For now, SARS treatment amounts to keeping patients isolated and dealing with their symptoms while the infection runs its course.
The drug ribavirin is being used by doctors in Hong Kong and Toronto who are convinced it helps many SARS patients. But U.S. researchers, who have been skeptical all along, shelved a plan to formally test the drug with a careful experiment in people.
The decision was made this week after testing at the U.S. Army Medical Research Institute for Infectious Diseases at Fort Detrick, Md., found no evidence that the drug has any effect against SARS virus growing in tissue cultures.
Dr. Catherine Laughlin, virology chief at the National Institute of Allergy and Infectious Diseases, said there was simply no evidence it worked. “It has significant toxicity, and there was a real chance you could do more harm than good.”
Viruses are much harder to kill than bacteria, and only three dozen antiviral medicines are on the market in the United States. None is specifically aimed at the coronaviruses, the family that includes the SARS virus as well as some that cause common colds.
Laughlin said ribavirin is the only drug conclusively shown ineffective in the Army experiments so far, and lab testing is under way or will begin this week on all the other antiviral drugs on the market. These are 16 AIDS drugs, 13 herpes drugs and seven aimed at flu and other viruses. Also to be tested are seven forms of interferon, which are the body’s natural microbe killers.
“Certainly there isn’t an upfront rational reason to think any of those would work,” she said. “But if any of them did, it would be extremely valuable, because they are available and understood.”
The best chance of success may be with about 30 drugs not yet approved but already in testing for other purposes. All are aimed at viral processes similar to those in the coronavirus. These include drugs that may prevent the virus from sticking to human cells or that block some of the steps the virus takes to copy itself.
Depending on how far along they are in human testing, some of these drugs could be available for SARS fairly quickly. But if none looks promising in Army testing, prospects become more remote. Drug companies have sent in hundreds of others for screening, but it would take years to prove their safety and effectiveness.
Laughlin said the government also plans a study of the natural history of the disease in hopes of finding more clues to treatment. Questions include whether lung damage in SARS results from the virus or the body’s overly enthusiastic efforts to kill it.
In the first days of an infection, before the body gears up production of antibodies, it uses interferon as an all-purpose virus fighter. Sometimes, however, too much interferon actually is harmful.
“If we find they are already swimming in interferon, no more would help,” Laughlin said. But if it turns out they make too little, interferon could be an important SARS treatment.
Dr. Frederick Hayden of the University of Virginia noted that studies in the 1980s showed spraying interferon up the nose blocks infection by the coronaviruses that cause colds. The spray was abandoned for colds because the drug irritates the nose, but it still might be a way to guard against more serious SARS infections.
Some experts worry that it may be too soon to give up on ribavirin. Dr. Michael Lai, a coronavirus expert at the University of Southern California, said its failure in the test tube does not prove it worthless in people, since the drug might somehow bolster immune defenses.
“I don’t disagree with the decision not to start a large-scale clinical trial,” Lai said. “But in the absence of specific drugs, if a clinician feels ribavirin works in some patients, they should continue to use it.”
Hayden suggested at least trying ribavirin in monkeys, which also can catch the SARS virus. “I’m still of the mind what we need is a controlled clinical trial,” he said, “although I can understand the reluctance to proceed until there is more supportive evidence.”
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EDITOR’S NOTE: Medical Editor Daniel Q. Haney is a special correspondent for The Associated Press.
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On the Net:
NIAID site: http://www.niaid.nih.gov/factsheets/sars.htm
AP-ES-04-22-03 1426EDT
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