HIV research at Mizzou eyes enzyme

COLUMBIA, Mo. -- A team of scientists led by a University of Missouri researcher believes it has found a new "soft spot" in the structure of HIV, the virus that causes AIDS.

"If we know what the lock looks like, we can make the key," said Stefan Sarafianos, who conducts research at the Bond Life Sciences Center.

Sarafianos is working with researchers at the University of Pittsburgh and University of Minnesota to design drugs that target an enzyme in HIV that currently is not targeted by other drugs. Sarafianos and his colleagues believe they know enough about the structure of the RNase H enzyme that the National Institutes of Health awarded a $3.4 million grant to fund the new drug-development program.

The aim is to produce a drug that will be available as a new treatment when HIV mutates to become resistant to current drugs. Sarafianos has in mind a new drug that would inhibit the progression of the virus so that HIV could become a more "manageable disease," in the same way that patients with diabetes and other chronic illnesses manage those conditions.

"You can't cure HIV, you can inhibit the viral load of HIV" in a patient, he said. "You do not eradicate the virus. The virus is there, in very, very small amounts, but it is there."

More than 1.1 million people in the United States live with HIV infection, and one in five are unaware they are infected. HIV is one of the world's leading infectious killers, claiming more than 25 million lives during the last three decades.

Michael Parniak, co-investigator for the NIH-funded project and professor of microbiology and molecular genetics at the University of Pittsburgh, said there are no drugs currently in development for RNase H, one of four HIV enzymes, partly because it is difficult to target. Parniak has identified more than 3,000 leads for compounds that could target the enzyme, and he said that's where Sarafianos' expertise in crystal structures will come into play.

"He has the perfect combination of skills and knowledge to move this project forward," Parniak said. "If anyone can solve this, it's him."

The compounds that show the most promise for development will be synthesized at the University of Minnesota.

The new project also gave Sarafianos an opportunity to tout the "multiple returns" on research grants and the amount of money awarded for HIV/AIDS research.

"We really make sure we're good stewards of public funds," Sarafianos said. "Research is not a luxury. It is an investment. Yes, we give a lot of money for this disease, but you get it all back" in benefits to society.

The perplexing HIV enzyme targeted by the research shares traits in common with hepatitis B. That virus kills roughly 600,000 people worldwide every year and some 300 million people are infected.

"We can make strong headway" toward new hepatitis B drugs," Sarafianos said, "with the same investment."

Sarafianos, an associate professor of molecular microbiology and immunology in the MU School of Medicine, said the HIV research team believes it has promising leads, but the process is far from clinical trials and final development of a new drug.

"You're talking many years," Sarafianos said. "There are no magic bullets out there. It's hard, hard work."

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