A new family of anti-viral compounds has proved 100 times more potent than the original in laboratory studies and opened a promising new direction in AIDS research. These related developments are described in the current (December 6) issue of the Journal of the American Chemical Society and the December 29 issue of the Journal of Organic Chemistry. Both publications are peer-reviewed journals of the American Chemical Society, the world's largest scientific society.
The compounds, called guanidinoglycosides, are intended to prevent HIV from forming and spreading throughout the body, according to Yitzhak Tor, who led the research team at the University of California, San Diego. Chemically modified from existing antibiotics known as aminoglycosides, the new compounds target the genetic structure of the virus essential to its replication, he said.
Specifically, they target the "Rev" protein that is responsible for producing and spreading HIV-infected cells. Without this protein, viral cells would be unable to reproduce and the disease would be disarmed, Tor said. By working with the virus's genetics, the researchers have found a place less prone to mutations that could lead to drug resistance, he added.
"If we can use drugs that prevent Rev from creating new viral cells, the HIV genetic material becomes useless," Tor said. "While numerous other groups explore more traditional approaches to anti-viral therapy, we believe that certain sites - like the rev intersection site - are promising and underutilized targets for anti-HIV drug design."
Aminoglycoside antibiotics have not been used to treat HIV because of their side effects and inefficiency in preventing the spread of the virus, Tor said. Guanidino groups are more promising, he believes. But it will be years before human testing could begin.
"We think this is an important direction for HIV research," Tor said. "We hope these compounds can inhibit the interactions that allow the HIV to spread. This area is still in the dark ages, so there's plenty of opportunity for progress."
The research cited above was funded by research grants from the U.S. National Institutes of Health and the University of California AIDS research program.
The online version of the research paper cited above was initially published November 17 on the journal's Web site. Journalists can arrange access to this site by sending an email to newsroom@acs.org or calling the contact person for this release.
Yitzhak Tor, Ph.D., is an associate professor in the department of chemistry and biochemistry at the University of California, San Diego in La Jolla, Calif.