Researchers Open New Leads in Anti-HIV Drug Development, Using A Compound Found in Nature
Published:23 May2024 Source:University of Michigan
A team of University of Michigan researchers has successfully modified a naturally occurring chemical compound in the lab, resulting in advanced lead compounds with anti-HIV activity.
One key to HIV's ability to remain hidden in patients' cells is a protein that the virus makes, called Nef. A chemical found in nature can inhibit HIV Nef, allowing the immune system to find and eliminate virally infected cells: a compound called concanamycin A (CMA), which is produced by a soil-derived microorganism. The first challenge the team had to overcome was supply. Another major challenge with developing CMA as an anti-HIV drug is that Nef is not CMA's primary target. With this latest research, the team has overcome both of these challenges. Using bioengineering, Sherman's team was able to develop a bacterial strain that increased CMA production 2,000-fold. Synthetic chemists in the lab then created more than 70 new variations of the compound, swapping out different chemical groups, to test for their potency against HIV Nef.
The team now has several CMA analogs that show high potency in blocking HIV Nef at very low dosage levels, without interrupting off-target effects or causing toxicity in human cells. They caution, however, that several important steps remain before the compounds would be ready for further testing in a clinical setting.