Stanford researchers synthesize compound to flush HIV out of hiding

...out of hiding and into the crosshairs

Any hunter will tell you that when your quarry goes into hiding, you have to flush it out to get a good shot at it. Such is the case with HIV, the virus that causes AIDS.

Though antiretroviral "cocktails" can target an active infection, they cannot get at the virus when it retreats inside the host's T cells, where it may lie dormant for decades, waiting for an opportunity to burst forth in a fresh round of infection. What HIV hunters need is a good bird dog.

Now, Stanford chemist Paul Wender and his coworkers have found a way to synthesize better bird dogs, agents that can be tailored to flush HIV out into the open where the immune system and antiretroviral therapies can destroy it. Wender is senior author of a paper about the research in the May 2 issue of Science.

"We're not sure how far this will go, but certainly, from a theoretical point of view, it has promise of taking therapy to the next level-that is, addressing issues related to eradication of the disease, of the virus, at least," said Wender, the Francis W. Bergstrom Professor.

Wender and his co-workers Jung-Min Kee and Jeff Warrington have developed a way to synthesize prostratin and DPP, two compounds that occur naturally in plants, in the laboratory. Prostratin, found in the Mamala plant (Homalanthus nutans) that grows in the Samoan rainforest, has shown promise in previous studies as an activator of dormant HIV. DPP, a molecular relative of prostratin found in resin spurge (Euphorbia resinifera), which grows in arid regions, also has shown potential.

Research has been hampered, though, because the compounds are difficult to obtain, particularly in the quantities needed for practical lab work on their mode of action and therapeutic potential. The yield from both plants is low and highly variable; the availability of the plants is limited; and isolating the compound is difficult. Heavy harvesting of the wild plants, especially in Samoa, also could cause ecological damage.

But synthetic prostratin and DPP, which now can be readily made in the lab, changes that equation.

"We have now minimized, if not eliminated, the issue of availability of prostratin and DPP," Wender said. "But equally, if not more importantly, we have opened access to other compounds that might be similar in structure but superior in function."