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New Compound Slows HIV Replication

It could mean development of new class of drugs, researchers say

WEDNESDAY, May 28 (HealthDay News) -- A new compound that inhibits HIV protease has been developed by researchers at the University of Michigan.

The protease, which is necessary for HIV replication, is a common target in the treatment of HIV patients. But this is the first new HIV protease inhibitor compound to be developed in 20 years and could lead to a new class of HIV/AIDS drugs, according to the researchers, who created the compound using computer models and then confirmed its effectiveness in laboratory tests.

This new compound debilitates the HIV-1 protease in a different way than current protease inhibitors, which bind to the center of the protease, freezing it closed, and preventing it from processing the proteins needed to assemble an active virus.

The new compound targets a different area of the protease and holds it open, which also inhibits its activity.

"In a way, this works like a door jam. If you looked only at the door when it's shut, you'd not know you could put a jam in it. We saw a spot where we could block the closing event, but because everyone else was working with the closed form, they couldn't see it," principal investigator Heather Carlson, a professor of medicinal chemistry in the College of Pharmacy, said in a prepared statement.

The new compound's molecules are smaller, which means they're absorbed much more easily.

"This new class of smaller molecules could have better drug properties (and) could get around current side effects," Carlson said. "HIV dosing regimes are really difficult. You have to take medicine several times a day. Maybe you wouldn't have to do that with these smaller molecules, because they would be absorbed differently."

Research into this new compound is still in the preliminary stages, she noted.

"It's very easy to make an inhibitor, [but] it's hard to make a drug. This compound is too weak to work in the human body. The key is to find more compounds that will work by the same mechanism," Carlson said.

More information

The National Institute of Allergy and Infectious Diseases has more about HIV treatment.

-- Robert Preidt

SOURCE: University of Michigan, news release, May 14, 2008

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