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Progress in Developing New Type of AIDS Drug
http://www.sina.com.cn 2004/07/12 14:53  新浪英语

  Berman report
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  Scientists say they have high hopes for a drug that could one day provide a new form of treatment for HIV-AIDS. A compound, which interferes with an elusive protein used by the HIV virus to infect human cells, has worked extremely well in monkeys. If the drug proves effective in human trials, scientists say, it could bolster the effectiveness of two existing AIDS drugs, particularly in fighting drug-resistant strains of the virus.

  Researchers at the pharmaceutical company Merck are very excited about an experimental drug, which has worked as well in monkeys infected with a primate version of the virus as any of the existing anti-AIDS drugs.

  It works by blocking one of three proteins, or enzymes, the HIV virus uses to gain entrance into and infect human immune system cells.

  Inhibitor drugs have been developed to block two of the proteins, to slow progression of the disease after infection. They have become standard therapy as a "cocktail" for people infected with HIV.

  Those enzymes are reverse transcriptase and protease. The first converts the virus' genetic material into that of its host cells. The second chops up the resulting larger proteins into smaller pieces, producing smaller viral particles that infect new cells.

  The third prong of cellular attack is a protein called integrase, which experts say has been harder to block. Once HIV fools host cells by changing its genetic information so it can enter them, integrase acts like a cut and paste operation in a word processor, deleting an immune cell's genetic material and replacing it with its own.

  An integrase inhibitor would give doctors a third line of attack against HIV infection, according to virologist Daria Hazuda of the division of Virus and Cell Biology at Merck.

  "This would offer a third class of anti-retroviral medications that can be combined with reverse transcriptase inhibitors and protease inhibitors. And since it is a new mechanism of action, these compounds are active against multi-drug resistant variants. So variants that have been selected in HIV-patients that are resistant to all current therapies," she said.

  Current anti-AIDS drugs eventually become resistant to therapy, or stop working, because the virus changes its shape.

  While researchers are encouraged by the success with the compound's effectiveness in monkey trials, developing a drug that is equally effective in humans can be difficult.

  Steven Young is executive director of the Department of Medicinal Chemistry at Merck. He says, if scientists find a compound that is equally effective in people, the company would ask U.S. regulators to speed approval of the drug.

  "Yeah, I really think that's what we're hoping for," he said. "I mean, we need to get data that show it has robust anti-viral effects in people. And if we're able to get that data, I think we would petition for fast track status."

  Dr. Young says an integrase inhibitor has the potential to prevent drug resistance.

  "To ensure our best chances of preventing resistance, we would give this as part of a cocktail therapy," he added. "And I think it's really our plan that we would test this with reverse transcriptase inhibitors and protease inhibitors, as well."

  The work on integrase is published in the current issue of the journal, Science.




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