New Compound Developed At UB May Be Effective Against Hiv, Even When It Mutates

Release Date: November 17, 1996

BUFFALO, N.Y. -- AIDS researchers have long sought a treatment that would work, even in the face of the virus' uncanny ability to mutate.

Now, University at Buffalo researchers have reported promising results with a new, anti-HIV compound they designed and synthesized that seems to be effective when a virus mutates.

Jui Wang, Ph.D., professor of chemistry and Einstein Professor of Science at UB, said the new compound has inhibited reverse transcriptase, the critical enzyme in AIDS virus replication.

In in vitro studies, he added, it has inhibited this enzyme in HIV-1, HIV-2, AZT-resistant HIV and a strain of HIV that is resistant to Nevirapine, a drug being used to treat AIDS.

"In addition, this compound was also able to inhibit the reverse transcriptase enzymes from two other viruses, which differ extensively in their amino-acid sequences from the HIV reverse transcriptase," Wang explained. "These results imply that the compound probably is mutation-insensitive and, therefore, should be effective against all retroviruses with similar reverse transcriptase structures."

He reported the results on Nov. 21 at a meeting on "Novel HIV Therapeutic Strategies" held in McLean, Va., by Cambridge Healthtech Institute.

Wang said an important reason for the new molecule's efficacy is that it fills the entire binding cleft of HIV-1 reverse transcriptase.

It is the first potential anti-AIDS molecule that has demonstrated an ability to do this.

Wang said that because its binding is not dependent on specific amino-acid residues, the compound would not be compromised if some of them change as a result of viral mutation.

"Because the molecule fits into the whole cleft of the virus, it prevents reverse transcriptase from making viral DNA, thereby preventing viral replication," said Wang.

The compound, poly-2'-O-(2,4-dinitrophenyl)-poly (A) (DNP-poly A), is an oligonucleotide inhibitor, the first that permeates the viral envelope and cell membrane and which is not degraded by ribonuclease.

So far, in vivo studies conducted by the UB group using an improved version of this DNP oligonucleotide on mice infected with leukemia have shown that the new compound also eliminated the presence of this virus in the blood.

"After treatment was stopped for two months, the virus did not return," said Wang.

According to Wang, those studies show that even at very low dosages, such as .25 mg per kg of body weight, the compound is able to stop the replication of a retrovirus similar to HIV.

A patent was issued on the compound earlier this year and a second patent on it has been filed.

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Ellen Goldbaum
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Medicine
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goldbaum@buffalo.edu
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