Developing new drugs to battle resurgence of malaria

With a warming climate comes the threat of expanding habitats for mosquitos that carry malaria, but researchers are using sophisticated synchrotron techniques in the quest for new treatments for the deadly disease.

While most cases of Malaria occur in sub-Saharan Africa, Central and South America, and Southeast Asia, “mosquito areas are spreading,” explained Dr. Oluwatoyin Asojo, adjunct professor of biochemistry and cell biology at The Geisel School of Medicine at Dartmouth College in Lebanon, New Hampshire. Warmer temperatures are helping the mosquitos return to breeding grounds “in places where we haven’t seen it (malaria) since the early part of the 20th century,” like North America and parts of Europe.

According to the World Health Organization’s most recent World Malaria Report, there were 262 million cases of the disease worldwide in 2023 and 597,000 deaths. Almost all the deaths occurred in Africa.

Given the risk of new malaria spread and growing drug resistance to conventional quinine-based therapeutics, new options are needed “so we’ll have an arsenal of tools ready,” she said. Asojo is part of an international team of scientists and students using the Canadian Light Source (CLS) at the University of Saskatchewan to study treatments targeting the malaria-causing parasite Plasmodium vivax (P. vivax). The challenge with P. vivax is that it can remain dormant in the human liver for years or even decades, then enter the blood and cause symptoms.

The team recently found a compound (IMP-1088) that binds in the parasite with an enzyme called N-myristoyltransferase or NMT, which also occurs naturally in humans. This binding inhibits all stages thus disrupting P. vivax’s lifecycle.

The advantage of focusing on NMT as a treatment “is that some NMT inhibitors have already been tested and used for different disease, giving us an edge,” said Asojo. Repurposing proven inhibitors to specifically attack the P. vivax enzyme is cost-effective, she said, but may have “less toxicity, by them not interacting as strongly with human NMT.”

The team will continue working to modify the inhibitors based on data they generated using the CLS, Asojo said, adding that synchrotron technology provides the high-quality, high-resolution data “pivotal to understanding the structure of these proteins. This may not appear to lead to splashy, glossy discoveries … but it’s key to understanding how proteins and other biomolecules work within the human body.”

An additional benefit to the team’s work at the CLS is “it allows us to train students, the next generation of scientists, who are going to keep us ahead of emerging and resurging infections, which we’re having a lot of.”

This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No.: 75N93022C00036

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Mendez, Alex, Cydni Bolling, Shane Taylor, Stanley Makumire, Bart Staker, Alexandra Reers, Brad Hammerson et al. "Structure of Plasmodium vivax N-myristoyltransferase with inhibitor IMP-1088: exploring an NMT inhibitor for antimalarial therapy." Structural Biology and Crystallization Communications 81, no. 1 (2025). https://doi.org/10.1107/S2053230X24011348

Photos: Canadian Light Source | CMCF Beamline | Researcher

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