U-M researchers open new leads in anti-HIV drug development, using a compound found in nature

March 11, 2024

Kathleen Collins, professor of microbiology and immunology at the U-M Medical School, and her lab have studied the Nef protein, the key to HIV's ability to remain hidden in patients' cells, for more than 15 years, investigating how it works and how it can be disabled. She and David Sherman, professor at the U-M Life Sciences Institute, previously discovered that a chemical found in nature can inhibit the protein : a compound called concanamycin A (CMA), which is produced by a soil-derived microorganism.
In its natural form, however,  the potential medicine CMA presents several challenges, ranging from the difficulties in lab-producing to Nef not being the primary target of CMA.
With the 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. They caution, however, that several important steps remain before the compounds would be ready for further testing in a clinical setting.
"We have engineered microorganisms to produce sustainable supplies of the natural product molecules and have really good chemical methods to make new analogs. And we have the methodologies in place to continue tracking the critical toxicity and potency parameters to further reduce off-target effects, " Sherman, another professor at the U-M College said.

From: EurekAlert!