Merck May Have AIDS Breakthrough
by
Lauran Neergaard,
AP Medical Writer

3:01 PM EST; January 27, 2000; Washington, D.C. (AP) -- Scientists have become increasingly frustrated in the hunt for novel ways to attack the AIDS virus, but now they're getting some encouraging news: Drug giant Merck and Co. has mapped the way toward a long-elusive target. It will take years of additional research to turn the finding into a usable medication, experts cautioned. But the research gives scientists another -- and long-awaited -- place to aim at in fighting the HIV virus, important as today's AIDS drugs slowly lose their edge with few options in sight. It's called integrase, an enzyme carried by the AIDS virus that causes a crucial step in HIV infection: It melds HIV's genetic material with the patient's own DNA inside their cells, essentially hijacking cells. Only then can HIV begin reproducing at its infamously furious rate.

Scientists have long known about integrase's crucial function and tried to create "integrase inhibiting" drugs to block its effect, much like the popular AIDS-fighting "protease inhibitors" block the action of a different HIV enzyme called protease. But attempts to create integrase inhibitors have failed so far. Merck's advance, reported in Friday's edition of the journal Science, was to uncover the exact spot in the enzyme's action that must be blocked for an integrase inhibitor to work. Merck researchers screened 250,000 samples in the company's library of chemicals and found two compounds known as "diketo acids" that hit that spot. In laboratory tests, the compounds successfully inhibited integrase and fought HIV.

In an unusual move, Merck executives refused to allow the lead scientist -- Daria Hazuda -- to discuss her discovery with reporters! But a Merck spokesman said the compounds described in Science have certain problems that prevent them from being pursued as drugs, so the company is hunting better candidates. Other AIDS researchers welcomed the news.

"It's opened up a third target, a target everyone knew was out there but ... that no one's been able to hit," said Cornell University's Dr. Jeffrey Laurence, senior scientist for the American Foundation for AIDS Research. "It's nice to know it's doable." "They have now developed methodology, which is a critical step in developing drugs against this target," added Dr. Douglas Richman of the University of California, San Diego. "It's very exciting."

Doctors today have two ways to attack HIV: Drugs like AZT and ddI block an enzyme called reverse transcriptase that is vital to early HIV infection, while protease inhibitors work at one of the latest stages of HIV replication. Combinations of those drugs have helped thousands of patients live longer and healthier, but they are not a cure, don't help everyone, and lose their effectiveness over time. Integrase inhibitors would target HIV infection between the steps those other drugs hit.

"What would be ideal ... would be to have drugs targeted at each of the successive steps of the virus life cycle, so if you didn't hit it at one step, you would get it at subsequent steps," said Dr. Mark Feinberg of Emory University. The integrase research "is an important step in the right direction."