June 28, 2000 Integrase Inhibitor May Prevent HIV from Taking Over Healthy Cells
Researchers have created a new molecule that appears to survive in cells longer than existing treatments to combat the virus that leads to AIDS, according to a new study reported in the June 21 edition of the peer-reviewed Journal of the American Chemical Society, published by the world’s largest scientific society.
The new molecule, called a dinucleotide, has been created in the laboratory of Vasu Nair, Ph.D. at the University of Iowa, using complex molecular engineering techniques. No human or animal testing has been done and much more testing is necessary before the compound can become a drug, he noted.
Drugs to arrest the effects of other viral enzymes that lead to HIV are currently in clinical use to stop the infectious chemical chain reaction. The virus, however, often overcomes these drugs — including well-known AZT — through development of resistance. Promising preliminary lab results show that the new integrase inhibitor molecule may possess the ability to withstand the body’s attempts to block its actions, said Nair, who was lead author of the study.
More than 40 million people worldwide are infected with the human immunodeficiency virus, referred to as HIV, which leads to AIDS. Current drug treatments face ongoing problems with drug resistance and toxicity, making the current study relevant to the next generation of AIDS medical treatments.
The compound is designed to stop HIV infection by preventing the virus from spreading to non-infected human cells. Called an HIV integrase inhibitor, the potential drug stops a key step that allows the virus to infect people, Nair said. The work was done in collaboration with the National Institutes of Health.
“I feel excited about this as a basic advancement in the science of inhibitors of this virus,” Nair said. “Most therapeutic advances start this way, with scientific discoveries such as this.”
HIV infection is a multi-step process, where the virus penetrates the body’s cells and begins to replicate itself. The virus uses its own enzymes and reproduces itself through the body’s own biochemistry.
An early major step involves a viral enzyme called reverse transcriptase that creates the DNA of the virus. The next step involves the HIV integrase enzyme, which allows the virus to take over normal human cells by “integrating” the viral DNA into the cells. Once integrated, the virus can reproduce itself. A subsequent third enzyme, protease, allows the virus to continue to replicate itself and spread the infection from cell to cell.
Development of a potential solution to stopping integrase, which inserts viral DNA into healthy cells, would allow doctors another chance to stop the onset of AIDS if the other drugs are unsuccessful. It is not a vaccine for the virus, but ideally it may represent another approach to combating the spread of the disease, Nair said.
“The integrase step is the most critical step in my point of view, because this is where the (viral) invasion is complete,” Nair said. “From a scientific point of view, this is the step in which the real damage is done.”
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