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FDA approves HIV drug NNRTI Rilpivirine (TMC-278) developed by University researchers
  By Mital Gajjar
Published: Sunday, September 11, 2011

The United States Food and Drug Administration recently approved antiretroviral drug Edurant, created by a team of researchers under the supervision of Edward Arnold, a University professor of chemistry and chemical biology.

HIV/AIDS became an important disease in the 1980s, and the team decided to put emphasis on understanding HIV and how the virus carries out its deadly business, said Arnold, resident faculty member of the Center for Advanced Biotechnology and Medicine.

"One of our major goals has been to use information about viruses so we could successfully develop drugs to treat diseases caused by viruses," he said.

The team of researchers studies the structure and function of viruses and other key parts of living systems that are relevant for health and disease, and established a laboratory at the University with part of the goal to understand how viruses work, he said.

To find a target drug to the virus, the team decided to study reverse transcriptase, an enzyme that copies the RNA genetic material of HIV and makes the DNA version of it, Arnold said.

"This is an essential part of the virus replication and drugs targeting reverse transcriptase can block this process," he said. "We thought knowing the structure of reverse transcriptase would be valuable."

Researchers learned the structure of HIV-1 reverse transcriptase using X-ray crystallography, which allows them to take accurate pictures of molecules, Arnold said.

"I engineered HIV-1 reverse transcriptase so that it would crystallize with Edurant and give a high-resolution structure showing the exact interactions between the drug and reverse transcriptase," said Joseph Bauman, research associate at Center for Advanced Biotechnology and Medicine.

Arnold said they began to work with Paul Janssen, founder of Johnson & Johnson, in 1990 to develop drugs for targeting HIV using his "good" molecules to come up with perfect molecules in order to develop drugs through a multi-disciplinary effort.

"By 1998, we had some promising drug candidates, and in 2001 we came up with the best molecule that was very efficient in overcoming drug-resistance," he said.

One of the problems encountered while targeting HIV was drug resistance because the virus is constantly changing, said Kalyan Das, research professor at the Center for Advanced Biotechnology and Medicine.

"We try to overcome drug resistance, which can make even effective medicines fail," he said.

Bauman said the reverse transcriptase HIV-1 showed that Edurant overcomes common drug resistance mutations by moving in the binding pocket and making compensatory interactions.

The drugs developed by the pharmaceutical industry have allowed many HIV-infected people with access to these drugs and to regain their health, Arnold said.

"They still are infected by HIV, but they can expect nearly normal life expectancy and quality of life," he said.

Edurant has the best properties of anti-AIDS drugs in its class in terms of potency and activity against drug resistant HIV variants and can be taken in very low dose, Arnold said.

"This drug is very efficient compared to other drugs and a single small pill of 25 milligrams can be taken per day with minimal side effects," Das said.

Edurant is being introduced to the market, is easy to synthesize and can be sold inexpensively in its generic form, he said.

"Intelence, the previous drug created in the collaboration with Janssen, has made a marvelous difference to many people who had become very sick and then were able to regain their health completely," Arnold said.

The obstacle is how to reach all 40 million people infected with HIV and AIDS. Johnson & Johnson contribution is important because a generic version can be sold at low price, near the cost of producing it, which is unusual for a new drug, he said.

"Usually when a new drug comes out, it would be too expensive for the broadest application," he said.

Arnold said Johnson & Johnson has made a remarkable commitment to world health by allowing the sale of a generic version of Edurant immediately in the developing world.

"That is a special humanitarian contribution because the drug will be available to many people who need it most. What we hope for is that all the people infected can be treated by the most effective drugs," he said.

AIDS has many consequences for world health, and the team hopes these medicines can help people throughout the world.

"HIV is a permanent infection, and there is no way currently to stop the virus completely in the body," he said. "It was Dr. Janssen's goal is to have an impact on the world HIV problem."

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