Novel buckyball blocks AIDS virus enzyme.

In a strange twist of fate, scientists have found a particular type of buckyball -- one of the family of all-carbon molecules called fullerenes -- that inhibits the growth of HIV, the AIDS-causing virus.

Raymond F. Schinazi, a viral pharmacologist at the Emory University School of Medicine in Atlanta, and his colleagues report that a buckyball specially tailored to fit into the active site of a key HIV enzyme -- HIV protease -- paralyzes the virus, rendering it noninfectious in human cells grown in the laboratory. The fullerene is also toxic to the virus itself but does not appear to harm host cells. The team's report appears in the August JOURNAL OF ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.

While the scientists stress that this new compound is not a treatment for AIDS, they do maintain that the new results could lead to future compounds that might have medicinal value.

"This is not a drug for AIDS," says Schinazi. "But it appears to be the first practical biological application of buckyballs."

Schinazi and his colleagues report that the uniquely shaped, water-soluble "fulleroid" disarms the HIV virus and blocks HIV protease from cutting proteins, without damaging the infected cells themselves. The fulleroid showed antiviral activity in three types of cultured human immune cells infected with HIV. It also acted on the virus' reverse transcriptase, and thus inhibited HIV's ability to infect cells.

Restraining the researchers' enthusiasm, though, is the fulleroid's low potency, compared with AZT and other HIV enzyme-inhibiting drugs. To be useful as a drug, the fulleroid must be "at least 1,000 times more potent," says George L. Kenyon, a pharmaceutical chemist at the University of California, San Francisco, who aided in the fulleroid's development.

"I would say these fullernes represent a potentially interesting new lead," says Craig L. Hill, a chemist at Emory University who coauthored the report. "At the present time, however, the collective knowledge from the little research to date is insufficient to get truly excited [about]. Very little is known about the tolerance of these compounds in mammals."

The fulleroids that Schinazi used were the brainchild of Simon H. Friedman, a graduate student working in Kenyon's lab. While Friedman was searching for compounds to block HIV protease, a colleague jokingly asked, "What next, buckyballs?" Friedman didn't laugh. Instead, he called up a model of an HIV protease on his computer and saw that a buckyball would fit perfectly into the protease's active binding site -- if only the fullerene would dissolve in water.

Friedman sought the help of Fred Wudl, a fullerene expert at the University of California, Santa Barbara, who fashioned a water-soluble version with two charged arms to grasp the protease's binding site. In lab tests, the fulleroid did in fact fill the protease's cavity, thus inactivating it.

Friedman and his colleagues present their results in the July 28 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, along with a separate report by Rint Sijbesma, a chemist at the University of California, Santa Barbara, and co-workers detailing how to make water-soluble fulleroids.