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Potential HIV blocker discovered

Vinay Kumar

University of Iowa chemistry professor Vasu Nair and researchers at the National Cancer Institute in Bethesda, Maryland have discovered potential HIV-inhibiting molecules that could one day prove help treat AIDS, according to a University of Iowa press release.

Nair's findings appear in a paper scheduled for publication in the June 21 issue of the Journal of the American Chemical Society. Nair says that although his National Institutes of Health-funded discovery is at an early stage of development and years away from any potential human testing, it is significant for its ability to stop HIV and for the way in which it attacks the virus.

"The single most devastating step in the attack of human cells by the HIV virus is the incorporation, or integration, of viral DNA into human chromosomal DNA. We have found small, stable molecules that inhibit this integration," he says. "In five to 10 years time, one of the molecules or a closely related compound could become a drug targeted at the key step in the integration of viral DNA into human DNA. That would be a major advance toward strictly limiting the progression of AIDS."

The way in which the molecules work is analogous to the way in which glue can be used to prevent a key from opening a lock. Specifically, the integration of viral DNA occurs through a complex chemical process made possible by a viral enzyme, called HIV integrase that acts as a key to open human DNA for this incursion. Once the viral DNA has entered human chromosomal DNA, it cannot be stopped, as it exploits human cellular chemistry to reproduce itself and destroy the immune system. However, the molecules Nair and his colleagues discovered block this integration by attaching themselves to the HIV "key" so that it no longer has the necessary capability to facilitate the incorporation of viral DNA into human DNA.

"Blocking the biochemical steps by which this enzyme works is the key to thwarting its action and preventing the ultimate viral DNA invasion," he says.

Nair's co-workers on the discovery include UI chemistry department postdoctoral associates M Taktakishvili and S Pal, and his collaborators in the Laboratory of Pharmacology at the National Cancer Institute are Dr Y Pommier and Dr N Neamati. In addition, he acknowledges his former graduate student, Tamera Jahnke, currently professor and head of chemistry at Southwest Missouri State University, for her contribution to the initial stages of the work.

Nair, known for his work on antiviral compounds, was named UI Foundation Distinguished Professor of Chemistry in 1993 and has received various patents, research awards and grants. In 1998, he was elected a Fellow of the American Association for the Advancement of Science "for his contributions to the development of antiviral agents".

"This publication is just the tip of the iceberg. We may be able to design molecules that may be even better in combating AIDS," he says. "We need to be constantly finding new ways to fight HIV and other viruses."

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