New Generation of Drugs To Target Malarial Detoxification Protein

The fight against malaria has taken a big step forward with the granting of a U.S. patent for the development and use of drugs to inhibit the catalytic activity of heme detoxification protein (HDP).

The Plasmodium parasite that causes malaria feeds on the globin component of red blood cell hemoglobin. As the leftover free heme moiety is toxic, the parasite relies on its HDP to detoxify the heme and convert it into a new form called hemozoin. While many anti-malarial drugs were designed to inhibit the metabolic steps leading to hemozoin synthesis, these drugs often have adverse side effects and are progressively becoming ineffective due to increasing drug resistance.

Now, investigators at the Virginia Biotechnology Institute (Blacksburg, VA, USA) have successfully identified and isolated the parasite HDP. This protein makes an excellent drug target, as it is produced by the Plasmodium rather than being a host molecule.

"With HDP, you will be targeting a parasite-specific factor, which is absolutely unique, and that is a big plus in the field of drug discovery,” said Dr. Otto Folkerts, associate director of technology development at the Virginia Bioinformatics Institute. "New drugs developed with this discovery will have a huge impact. It is an entirely new mechanism of action and can help with the increasing problem of drug resistance, for example, as part of a cocktail therapy with other existing drugs.”

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Virginia Biotechnology Institute