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Discarded HIV Drug Gets Gold-Plated Second Chance


Since the beginning of the HIV epidemic in the 1980s, biochemical researchers have spent years and billions of dollars looking for medications to treat the infection. Some effective drugs have been found. But many other promising chemicals have had to be discarded. Now, as we hear from Rose Hoban, there may be a way to return them to the medical arsenal.

TAK-779 is one of the chemicals that showed some promise in attacking HIV, but it couldn't be used in humans because of its toxic side effects. But biochemist Christian Melander from North Carolina State University says TAK-779 and other drugs might be made safer with the addition of gold.

Melander says gold isn't harmful when given to humans medicinally. The metal can even be helpful. "Gold salts were traditionally used to treat rheumatoid arthritis, and actually is still used in developing countries," Melander explains. "Before the nonsteroidal anti-inflammatory drugs, people would just pump gold salts into people to relieve rheumatoid arthritis."

However, Melander says he wouldn't be pumping gold into HIV patients. He would improve some promising drugs by adding gold nanoparticles to them.

A gold nanoparticle is exceedingly small: 75,000 of them lined up side by side would be about as wide as a human hair. And metallic nanoparticles bind very tightly to the surface of cells.

Melander says researchers had found that the toxic part of TAK-779 was the portion of the molecule that binds to the surface of HIV. In his experiments, he replaced that part of the drug's molecule with a gold nanoparticle. The newly reconstituted drug attached itself to the surface of the virus very well.

"We were able to show that that actually worked," he says, "and we were actually able to reconstitute the activity of the drug based on not having to go back and redesign the whole molecule, but just chopping off the part that didn't work."

Melander says one of the advantages of using gold nanoparticles in pharmaceuticals is that they are so small. Because of their size, they can reach parts of the body that might be difficult to access for larger molecules. One of those areas is the brain - a part of the body protected by a network of blood vessels and membranes that keeps most drugs out. Melander says one thing they're trying to do in fighting HIV is deliver drugs to the brain and the rest of the central nervous system.

"A lot of drugs don't pass the blood-brain barrier and it's been shown that HIV will just form a latent reservoir of virus in your brain, because a lot of the drugs won't get there," Melander says. "So if we can deliver drugs to the brain using this targeted approach, and then have the drugs on the nanoparticles so that they are robust, we can think about targeting places where current drugs don't reach."

Melander says he's only done this work in the chemistry lab and in test tubes. Next, he wants to try using nanoparticle-enhanced HIV drugs in experimental animals to help TAK-779 and other drugs be more effective.

Melander's research is published in the Journal of the American Chemical Society.

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