Scientists at the University of Utah have developed new peptides that appear to be significantly more effective at blocking HIV's entry into cells than other drugs in their class.

"Our 'D-peptides' offer several potential therapeutic advantages over existing peptide entry inhibitors, which are costly, require high dose injections, and suffer from the emergence of drug-resistance," said University of Utah biochemist Michael S. Kay, lead author on the paper. "In contrast, our D-peptides resist degradation, so they have the potential to be administered by mouth and last longer in the bloodstream. Since these inhibitors have a unique inhibitory mechanism, they should work well in combination with existing HIV inhibitors."

Using x-ray crystallography, the scientists discovered D-peptides with up to a 40,000-fold improved antiviral potency over previously reported D-peptides. Based on what is the structures, the peptides may also still be improved and engineered to reduce the chance of drug resistance. The study is published online on the October 8 issue of the Proceedings of the National Academy of Sciences.

Image: Structure of D-peptide inhibitors (green, yellow, and purple) bound to an HIV protein mimic in three "pockets" that are essential to the virus' ability to enter cells. Blocking the pockets thwarts entry and reduces infectivity. Credit: BNL