Stanford researchers synthesize compound to flush HIV out of hiding

"To the credit of my coworkers, Jung-Min Kee and Jeff Warrington, they employed a strategy that sometimes is missed," Wender said. "Rather than fighting the flow, they went with it." They found a way to redirect the chemical complications into a solution to the problem that proved even better than the route they had initially sought to follow.

"Eventually they produced a shorter, more economical way of connecting our starting material, phorbol, to our target, prostratin," Wender said. The process Kee and Warrington came up with requires only five steps, which is of tremendous importance in making it economically feasible. As Wender pointed out, "steps cost money and human time."

Wender emphasized that the work of his team is the most recent chapter in efforts of a truly global community, starting with the Samoan healers, who willingly shared their knowledge with Paul Cox, an ethnobotanist who saw them prescribing a tea made from Mamala bark for patients with hepatitis-like symptoms. Cox, in turn, sent samples to the National Institutes of Health, in hopes that the bark might have antiviral properties useful in fighting some cancers. Researchers at NIH then analyzed the bark and isolated prostratin.

Prostratin belongs to a class of compounds called tiglianes, many of which promote tumor growth, so it had no initially perceived use in fighting cancer. But NIH researchers found that prostratin was not a tumor promoter and checked to see if perhaps it could help combat HIV, which is when its remarkable ability to flush out the dormant virus was discovered. Significantly, prostratin has also been found to block uptake of the purged virus, offering yet another potentially therapeutic benefit.

"The whole effort is a testimonial to a global community working to deal with what I think is a global, and top priority, problem," Wender said.

The research was funded by the National Institutes of Health. At the time of the study, Kee was a doctoral candidate in chemistry and Warrington was a postdoctoral scholar at Stanford. Kee is now a postdoctoral scholar at Rockefeller University, and Warrington is working in the biotech industry.

The Joint United Nations Programme on HIV/AIDS estimates that 33.2 million people were living with HIV and 2.1 million people lost their lives to AIDS in 2007. Current antiviral therapies require lifelong treatment, and patients must consistently take doses of medication on a precise schedule, which creates compliance challenges for many of them. The antiviral drugs often become ineffective as the virus develops resistance and are exceptionally costly, the last a major problem in less-developed regions of the globe.