Malaria has been one of the world’s biggest killers for as long as records have been
kept. With resistance to existing antimalarial drugs on the rise, there is a renewed
push to find different ways to fight it. Two University of Houston (UH) engineers
have stepped up to the plate to answer the call.
Jeffery Rimer and Peter Vekilov, both with the department of chemical and biomolecular
engineering, recently were awarded a grant from the U.S. Department of Defense (DOD)
to create an entirely new platform for developing antimalarial drugs. Like existing
antimalarial drugs, this new platform will target plasmodium, which is the parasite
that causes malaria, by utilizing a quirk in the infection process.
Typically introduced into hosts through a mosquito bite, plasmodium enters a host’s
red blood cells where it consumes the hemoglobin by breaking it down. However, one
subunit of hemoglobin the parasite cannot use is heme, which is the part of the blood
that helps transport oxygen to the other parts of the body. Left alone, heme is highly
toxic – toxic enough, in fact, to kill the parasite and prevent an infection from
taking hold.
Unfortunately, as the parasite has evolved, it segregates the heme into little crystals.
If the heme is sequestered in crystals, it can’t kill the parasite. Existing antimalarial
medications presumably work by preventing the formation and growth of heme crystals.
As a result, heme molecules released by hemoglobin consumption usually are able to
kill the parasite. However, the effectiveness of these drugs has begun to wane.
Since the precise nature of how these drugs prevent crystal formation is unknown,
Vekilov and Rimer will work to uncover the process of heme crystal formation and then
determine what kind of molecules could inhibit crystallization. Vekilov believes that
heme molecules attach to crystals at kinks that are sites on the crystal surface favorable
for the addition of new heme molecules. If this is, in fact, how heme crystals grow,
the team will design “tailored inhibitors” that prevent the growth from occurring.
“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.”
While Vekilov and Rimer note that this research won’t likely result in the discovery
of specific molecules that could be developed into medications, they do say it will
provide a deeper understanding of the type of molecules that could be the basis of
new drugs. Helping drug developers understand how these medications could work would
allow them to create new antimalarial drugs in a more logical and cost-effective manner.
Currently, say the researchers, pharmaceutical companies screen libraries of molecules
to identify drug targets. This, they say, is a combinatorial approach that employs
an exhaustive, trial-and-error method. The UH team is working to replace this impractical
process with techniques to speed up drug development. If Rimer and Vekilov can develop
a better understanding of how these molecules bind to the crystal surface, researchers
could start thinking about designing antimalarial drugs in a much more rational manner.
The two-year $150,000 seed grant will be administered by the Alliance for NanoHealth.
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Editorial Note: High-resolution photos of Peter Vekilov and Jeffery Rimer are available
to media by contacting Lisa Merkl.
About the University of Houston
The University of Houston is a Carnegie-designated Tier One public research university
recognized by The Princeton Review as one of the nation’s best colleges for undergraduate
education. UH serves the globally competitive Houston and Gulf Coast Region by providing
world-class faculty, experiential learning and strategic industry partnerships. Located
in the nation’s fourth-largest city, UH serves more than 38,500 students in the most
ethnically and culturally diverse region in the country.
About the Cullen College of Engineering
For more than 69 years, the UH Cullen College of Engineering has played a vitally
important role in educating engineers in Texas. Its nationally competitive programs
are taught by innovative faculty, eleven of whom are members of the National Academy
of Engineering. The college offers degree programs in biomedical, chemical, civil,
computer, electrical, environmental, industrial, mechanical and petroleum engineering
with specialty programs in materials, aerospace and computer and systems engineering.
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