The decade-long research that chemistry professor Thomas Bell has invested in received an important boost recently when one of Bell's articles made the list of the 100 most influential publications in the HIV/AIDS research field for 2006. The research looks into the development of an extremely effective HIV/AIDS-fighting compound
Out of more than 10,000 HIV/AIDS research articles in the world, Bell's article in the Journal of Medicinal Chemistry was ranked at No. 90—an amazing feat given that the keywords "HIV" or "AIDS" are not even in the article's title.
"You'd think it would have a fairly small readership, but to have this article be one of the top 100 most influential articles published in 2006 in the entire field of HIV/AIDS research, is pretty impressive," said Bell, noting that the ranking is from the AIDS and HIV research portal, aidshivresearch.com
"We were No. 90 out of more than 10,000, so that's better than the 99th percentile."
Other researchers from throughout the world have flocked to the article because of the implications of Bell's work. Since Bell documented the activities of the so-called "CADA" (Cyclotriazadisulfonamide) compound more than a decade ago, researchers have increasingly recognized that CADA could represent the next generation in HIV/AIDS drugs.
CADA has been shown to inhibit replication of HIV by eliminating the "door handle" by which receptor molecules on the surface of a white blood cell normally would grab HIV, allowing the virus to enter and infect the cell.
"There's no other drug like it," Bell said. "If you look at the cell before and after it has been treated with the drug, you see something truly remarkable. Before being treated with the drug, you can count the number of CD4 (surface receptor molecules for HIV) on the surface of the cell. If you treat the cell with the drug for half a day, or a day, then the CD4 is almost gone. It's a completely novel mechanism of action in inhibiting replication of the virus."
Bell, a member of the College of Science, said that in the past few years, he and his research team have learned more about CADA and its properties. They have learned that very small amounts of CADA can protect the cell against HIV. Also, they have found that the compound's cellular toxicity on white blood cells is relatively low. This could mean that the therapeutic index that drug researchers use in evaluating side effects of a proposed drug could also be low—a good sign that humans could safely take the drug.
"Every drug is toxic, and the less toxic it is, the better," Bell said. "It takes about 50 times higher the amount of CADA to cause toxicity on the white blood cells than it does to give it protection against HIV, which is a positive indication that we're headed in the right direction."
Bell said that his work with Tibotec, a drug company in Belgium, has also led to important findings that could have far-reaching implications for developing nations that will be devastated in the coming years by the AIDS epidemic.
"Because of the novel mechanism of the action, there is a chance that this could be used not just to treat AIDS patients—because it does decrease the replication of the virus and the symptoms of the virus go away—but also it could be used to protect people from being infected in the first place," he said, noting that the presence of CADA would mean that cells would be incapable of being infected at all. "There's a European consortium that is looking at this drug as a potential 'microbicide,' which literally means 'killing the microbe,' but really it's any drug that can be used to prevent infection. It's being tested now as a protective agent, a prophylactic agent, in a vaginal implant.
"This could be used, for example, in countries where societal, cultural or religious norms say that men shouldn't wear condoms. It could also be used for technicians working laboratories where blood is handled from potentially infected patients."
And, having a rarified ranking in the 99th percentile of published articles in HIV/AIDS researcher will further help Bell in his work, he said.
"What I'm really excited about is in the last year we've finally gotten the attention of the pharmaceutical industry," Bell said. "The first few years, when we were working on this drug, I thought, 'Wow, a new AIDS drug ... the world will beat a path to my door.' And that didn't happen right away. Now, though, the work has reached a point of respectability and the pharmaceutical industry is recognizing the potential of this approach."