Army Testing Finds Drugs That May Stop the SARS Virus

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> Army Testing Finds Drugs That May Stop the SARS Virus

> http://ap.tbo.com/ap/breaking/MGAHFVXS9FD.html

> By Daniel Q. Haney The Associated Press

> Published: May 3, 2003

>

>

> FORT DETRICK, Md. (AP) - The first strong evidence that medicine will

> eventually defeat the SARS virus has come to light in recent days at the

> Army's biodefense labs, where the world's most intensive and systematic

> search for a cure is going on around the clock.

> Scientists are concentrating on antiviral drugs already in drugstores,

> hoping to find something that will quickly help people dying from the

> new respiratory disease.

>

> While most of these medicines have failed so far, one category has

> popped out as promising - the natural infection-fighting protein

> interferon. <<< ED NOTE: NO! NO! NO! See:

> http://www.who.int/emc-

documents/hepatitis/docs/whocdscsrlyo20022/treatment/side_effects.html

>

> At the same time, the scientists have tested a few experimental

> compounds that seem especially intriguing, based on what they know about

> the internal mechanics of the SARS virus. The potentially pivotal

> result: Drugs called protease inhibitors, chemical cousins of the

> medicines that defeated AIDS, can stop the SARS virus cold. <<< ED NOTE:

> DITTO! See:

> http://www.hivpositive.com/f-Treatment/5-Treatments/ProteaseYou/prot10.html

>

> These hits, as the scientists call them, are just the first step in

> finding possible treatments for SARS. All the tests are done in lab

> dishes, and treatments that work spectacularly on that level can be

> disappointing in people. In the months to come, they expect to test at

> least 100,000 compounds, perhaps even 500,000.

>

> Nevertheless, the scientists are exultant that their search has so

> rapidly turned up leads to take into more elaborate experiments.

>

> " It's a pretty big deal. We are excited about it, " says Peter Jahrling,

> senior research scientist at the U.S. Army Medical Research Institute of

> Infectious Diseases at Fort Detrick.

>

> USAMRIID's usual work is finding defenses to the contagion troops can

> encounter, intentionally or by chance, anywhere on the planet. These

> scientists' expertise in handling odd, poorly understood and dangerous

> bugs made them a natural choice for drug screening when severe acute

> respiratory syndrome emerged in Asia as a never-before-seen form of

> pneumonia.

>

> John Huggins, who is in charge of antiviral drugs, went to work

> methodically infecting living cells with the SARS virus to see if

> something, anything, will keep the cells alive.

>

> About 20 people work at Huggins' level 3 biosafety lab - one step down

> from the most secure - housed in a blank-walled World War II relic

> across the lawn from USAMRIID's headquarters. In these beginning days,

> they are testing any medicine that makes sense - and some with no

> biological plausibility at all - in search of quick hits.

>

> " Unfortunately, it is far better to be systematic than it is to be smart

> in these early steps, " says Huggins. " Trying to guess and blindly going

> where logic leads you is dangerous when you know so little. "

>

> By serendipity, they hope, something already in routine use will cure

> SARS. But of the several dozen tested so far, mostly standard drugs for

> HIV and herpes, only interferon has shown promise.

>

> Interferon is one of the body's general purpose virus-stoppers. It comes

> into play before the immune system gears up production of more precisely

> targeted antibodies.

>

> Duplicated through genetic engineering, interferon is available

> commercially in several different forms. The Army lab found that a

> variety called interferon beta blocks the SARS virus in the lab dish,

> although it takes 10 times more than would ordinarily be given to a

> patient. Still, experts say smaller doses might be effective inside the

> human body.

>

> While interferon appears to have the best chance of quickly becoming a

> treatment for the disease, Huggins says, extra testing is necessary to

> make sure it does more good than harm.

>

> Because the respiratory disease is brand new, no one knows exactly why

> it makes people so sick, in some cases destroying their lungs.

> Certainly, the virus itself is capable of great damage. But in some

> infections, the body's own over-the-top counterattack - including vast

> production of interferon - can be as bad as the bug itself.

>

> So before interferon becomes a SARS treatment, doctors will have to be

> sure patients are not already making more than enough interferon of

> their own.

>

> However, Dr. Frederick Hayden, a respiratory virus expert at the

> University of Virginia, notes that when the flu causes pneumonia, the

> body produces too little interferon to fight back effectively, so the

> Army lab results " raise the possibility of using interferon either for

> prevention or for therapy of SARS. "

>

> Experts are also encouraged to learn that drugs called cysteine protease

> inhibitors can stop the virus by jamming one of the enzymes it needs to

> make new copies of itself. Jahrling says the lab has tested 19 of them,

> and six work well. " They clearly inhibit replication of the virus and do

> so at concentrations that are not toxic to the cells. "

>

> The drugs were all created by pharmaceutical firms to treat or ward off

> colds caused by the rhinoviruses, but none of the six have been given to

> people. Because of similarities between the various respiratory viruses,

> scientists have hoped from the start that medicines aimed at colds and

> flu will turn out to be good for the SARS virus, too.

>

> Even if these particular ones are not perfect, something like them might

> be. So the lab will gather up lots of closely related compounds that

> were abandoned by pharmaceutical companies along the way.

>

> If interferon and other on-the-market medicines fail, the conquest of

> SARS will almost certainly be a slow business. Developers will have to

> work their meticulous way through each plodding step, proving that the

> medicine helps infected lab animals, that it is safe enough for people

> and ultimately that it cures the sick, first in experiments on a few,

> then on many.

>

> Because of SARS' urgency, drug development is likely to move at top

> speed, and Hayden predicts that a medicine such as a protease inhibitor

> could be ready for testing on people within a year.

>

> Meanwhile, Huggins' lab goes nonstop. It thoroughly tests about 25 drugs

> at a time and must wait three days for an answer. Soon, the team expects

> to scale up testing to 100 at once.

>

> Every drug gets a pair of 4-by-6-inch trays, each divided into 96

> separate compartments with varying concentrations of the medicine plus a

> layer of monkey cells. The scientists add enough SARS virus to infect

> one in 1,000 cells.

>

> As bad as the virus is for human lungs, it behaves obediently in the

> lab, growing robustly in these cell cultures. Under 40-times

> magnification, its destructive punch is obvious. The usual brick-like

> rows of cells puff up as the virus takes control. Some of them literally

> explode, leaving holes.

>

> If the drug works, the virus does not spread. Cells stay healthy. To see

> how they fare, scientists douse them with a dye that is absorbed by

> healthy cells. If they soak up a lot, they are doing fine, and the drug

> is effective.

>

> The lab is working with the National Institute of Allergy and Infectious

> Diseases and the Food and Drug Administration to round up anything that

> might work. They plan to test everything, within reason, that is offered

> by drug developers or anyone else with a good idea.

>

> " We have been pleasantly amazed by the number of pharmaceutical firms,

> large and small, as well as academic investigators who have offered

> compounds for screening, " says Catherine Laughlin, virology chief at the

> infectious disease institute.

>

> The government is not simply waiting for drugs to show up in the mail,

> either. The FDA is coaxing drug companies to submit possible antiviral

> drugs that the agency knows they are working on or may even have

> discarded.

>

> To be sure nothing is missed, the Army lab will eventually try every

> category of medicine sold around the world, no matter what it is

> intended for. It will screen all 880 drugs in a collection of chemically

> unique medicines maintained by Prestwick Chemical Inc.

>

> Much of the testing, though, will not involve the exhaustive screening

> given to the top prospects. Instead, the labs will load five drugs into

> each of the compartments on its trays, then go back and figure out which

> one was responsible if they get a hit.

>

> Already, the labs have screened 3,000 compounds with this quick

> run-through. And one of them, submitted by a small pharmaceutical

> company, stopped the virus. The next step will be to test the five

> separately to see which one did it.

>

> Some drug makers are anxious to get their compounds into the testing

> queue. For instance, AVI BioPharma has just finished crafting a possible

> drug intended to disable the virus' genes and is shipping it off to the

> Army lab.

>

> Testing there " lends tremendous credibility, " says Denis Burger, the

> firm's chief executive. " There is not another facility anywhere that

> matches this in terms of the muscle they can throw at it. "

>

> But until they understand more about what is likely to work, the Army

> scientists will entertain just about any idea. In fact, they say a high

> point of their day is looking at the SARS cures that well-meaning people

> propose out of the blue.

>

> Dried broccoli is Huggins' favorite. Elderberry syrup has come in at

> least four times. " Eucalyptus oil! " Jahrling says, skimming his e-mail.

>

>

> ---

>

> EDITOR'S NOTE: Medical Editor Daniel Q. Haney is a special correspondent

> for The Associated Press.

>

> ---

>

> On the Net:

>

> NIAID site: http://www.niaid.nih.gov/factsheets/sars.htm

>

> AP-ES-05-03-03 1215EDT

>