Stanford chemistry professor Paul Wender partnered with UCLA Professor Jerry Zack to publish their most recent breakthrough toward eradicating the HIV virus: the synthesis of a set of compounds that successfully tackle the latent, or dormant, virus for the first time.
The research, published in the July 15 issue of Nature Chemistry, discusses the creation of synthetic compounds, or bryologs, that can more effectively activate the dormant HIV virus. Currently, an AIDS patient undergoing highly active antiretroviral therapy (HAART) can reduce the active virus to undetectable levels, but the latent virus remains hidden in certain cells. That latent virus can activate gradually.
“And the current therapeutics cannot touch that [latent] virus,” said Jerry Zack, co-director of the UCLA AIDS center. “But if the individual goes off the medications, this latent [virus] rekindles infection, and the disease progresses again.”
In fact, the molecule that activates the ever-important latent virus has been a natural remedy for a long time. Healers in Western Samoa used the bark of the mamala tree to make tea to cure hepatitis. It turns out that the bark is rich in a molecule called prostratin, which can induce the expression of the normally dormant HIV virus. Then, antiretroviral drugs can be used to treat the patient.
Wender’s research into these bryologs, synthetic compounds with a similar structure to prostratin molecules, can activate the dormant HIV virus much more cheaply and effectively. He is enthusiastic about the potential application of his new compound to the HIV virus.
“[Prostratin] is the lead clinical candidate for targeting the latent virus,” he said. “We report [new synthetic] compounds that are 1000-fold better [at activating latent HIV] than prostratin.”
There are many HIV drugs on the market now, but Wender believes that the key to AIDS eradication is actually in the latent virus. The key is that current antiretrovirals can only target the active virus, and it is the latent virus that is the source of continuing infection. If it is flushed out of the system through bryologs, the rest of the virus can be taken care of with medication we have today.
That is not to say a permanent cure for AIDS can be expected in the near future. Much more work remains before Wender’s research can be applied to AIDS patients. The next stage for bryolog research will include in vivo (“in a body”) studies and preclinical testing. That, in itself, will pose a new set of challenges for the researchers.
“What’s coming down the road is a challenge to develop in vivo methods to test the drugs … in a model that isn’t in people since it could be harmful,” Zack said. “You can’t infect mice with HIV, but if you humanize them, you can infect the human cells with HIV, and you can test the drugs on that.”
Both scientists emphasized that their bryolog research still has a long way to go before it can be considered a practical solution to AIDS. But it has given some hope for the permanent eradication of HIV.
“Since the story broke, I’ve been flooded with emails, and they’re pretty remarkable,” Wender said. These people are … sharing with me that our article, our research, brought them a ray of hope … this is what keeps me up late at night and gets me up every morning.”