A chemical compound that's already showing success in cancer treatments may also hold promise in the fight against HIV.
The compound, EBC-46, otherwise known as tigilanol tiglate, may have immense potential for eradicating human immunodeficiency virus (HIV) infections.
A team of researchers from Stanford discovered that EBC-46 is particularly good at activating the dormant cells where HIV hides.
These 'kicked' cells can then be targeted and 'killed off' with immunotherapies to clear the virus from the body entirely.
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The scientists hopes this 'kick and kill' strategy could finally be the key to curing HIV once and for all.
“We’re pleased to report that EBC-46 performed extremely well in preclinical experiments as part of a ‘kick and kill’ therapeutic,” said study senior author Paul Wender, the Bergstrom Professor of Chemistry at Stanford’s School of Humanities and Sciences.
“While we still have a lot of work to do before treatments based on EBC-46 might reach the clinic, this study marks unprecedented progress toward the as-yet-unrealised goal of eradicating HIV.”
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The study, published in Science Advances, involved collaboration with researchers from UC Irvine and UCLA.
EBC-46 was discovered about a decade ago through automated drug screening by QBiotics, an Australian life sciences company.
The compound naturally occurs in a single rainforest species called the blushwood tree (Fontainea picrosperma), found only in Australia’s tropical northeast.
Essentially, EBC-46 interacts with an enzyme called protein kinase C (PKC), which is involved in major diseases like AIDS, cancer and Alzheimer’s.
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Since HIV first appeared in humans over 40 years ago, nearly 90 million people have been infected, and around 45 million have died, according to the United Nations Programme on HIV/AIDS.
Today, about 40 million people live with the virus, and nearly two million new infections occur every year.
Whilst the rise of highly effective antiretroviral therapies (ARTs) has made the once-lethal infection into more of a chronic, manageable condition, they come with a high cost, low access and lifetime adherence.
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That’s why finding a way to eliminate the virus is so important, said Wender.
“Part of the solution to the global HIV problem is addressing the 40 million people who are HIV positive,” said Wender. “Easing the medication burden and economic losses posed by the current HIV regimen, especially in developing countries, is critical.”
In their experiments, the Stanford team tested EBC-46 and 15 of its analogs (chemically similar compounds) on latent HIV-infected cells.
Latent cells act as hidden shelters for HIV, making it harder for the immune system and treatments like ART to attack the virus.
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Turns out, some analogs were four times more effective (90%) than the previous best-known agent, bryostatin, at 'kicking' these cells awake.
“Our studies show that EBC-46 analogs are exceptional latency-reversing agents, representing a potentially significant step toward HIV eradication,” Wender added.
Following their success with HIV-infected cells, Wender and his team have taken the next step to test their research on animal models. They have the long-term goal of eventually reaching human clinical trials.
“The fact that we may be able to make a dramatic difference in people’s lives with EBC-46 is what keeps us up late at night and gets us up early in the morning,” Wender concluded.