Magazine article Science News

New Compounds Inhibit HIV in Lab

Magazine article Science News

New Compounds Inhibit HIV in Lab

Article excerpt

When the human immunodeficiency virus (HIV) invades a cell, it produces three essential enzymes that direct the takeover. Two of these--reverse transcriptase and protease--have proved susceptible to inhibitor drugs. Mutations in the AIDS virus, however, have made some strains resistant to these medications (SN: 4/24/93, p. 261).

Scientists at Merck Research Laboratories in West Point, Pa., now report the discovery of two new compounds that sabotage the third viral enzyme, called integrase. By blocking integrase, these compounds interfere with the replication cycle of HIV-1, the most common strain of the virus. Although the researchers so far have confined their experiments to cells in laboratory dishes, the compounds are the first to clearly render integrase incapable of splicing viral DNA onto host-cell DNA.

"I think this is very promising," says W. Edward Robinson Jr., a virologist at the University of California, Irvine whose research team in 1996 isolated a less promising compound that blocks integrase. "This, combined with our data and [other findings], suggests we are getting closer to having molecules that act against integrase--and which can be used in people."

Tapping a corporate repository of natural and artificial chemicals, the Merck researchers tested roughly 250,000 substances before finding two that worked well. These acids, called L-731,988 and L-708,906, inhibited integrase in chemical tests. They also prevented for several weeks the spread of HIV grown in cell cultures and quelled strains of HIV that are resistant to other enzyme inhibitors, the scientists report in the Jan. 28 SCIENCE.

Upon entering an immune cell, HIV makes a DNA version of its viral genome. In the nucleus of the cell, HIV cleaves the host's DNA chain and, guided by integrase, inserts its DNA into the host genome.

Under direction from this integrated viral DNA, the cell changes its priorities and starts producing RNA and proteins that make copies of HIV. …

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