Malaria parasite quirk may lead to new antimalarial drugs

Engineers from the University of Houston are using a grant from the U.S. Department of Defense to investigate a quirk in the malaria parasite that may lead to a new platform of antimalarial drugs.

Jeffery Rimer and Peter Vekilov, both of UH’s department of chemical and biomolecular engineering, recently received a DOD grant to investigate a means to attack a quirk in the way plasmodium, the parasite that causes malaria, infects a host.

Once in the blood, plasmodium consumes hemoglobin by breaking it down. A certain subunit of the hemoglobin, heme, is unusable by the parasite. Heme, which helps transport oxygen throughout the body, is actually toxic and can kill plasmodium if in a high enough concentration.

Plasmodium is capable of segregating heme into small crystals. Existing antimalarials often focus on inhibiting crystal formation so that heme buildup can kill the parasite and prevent the infection. Existing drugs, however, have become less effective over time.

Rimer and Vekilov are seeking to uncover how the process of heme crystallization works and how to block it more effectively. They said that there are kinks in the crystals surface that favor the addition of heme molecules and that a “tailored inhibitor” can eventually be designed to prevent heme from attaching to them.

"A tailored inhibitor mimics the crystal building unit or units, which in this case is heme," Rimer said. "You want to design inhibitors with an affinity for binding to crystal surfaces. Certain parts of the inhibitor molecule then block adjacent binding sites. So, the inhibitors we plan to design will physically block the kinks and disrupt heme addition."

The scientists said that while their research will not result in any new medications, it can provide an understanding of what types of molecules can form the basis for a new antimalarial platform that is more effective than those currently in use.