Breaking the deadly cycle: dealing with malaria parasites at multiple life stages

Malaria is a mosquito-borne disease caused by Plasmodium.

Paul Kariye, a professor in the Department of Chemistry at the School of Science at Virginia Tech and director of the Drug Discovery Center at Virginia Tech, said that his colleagues received a US$3.

"Currently the most effective drugs for treating malaria are not safe for pregnant women or children under 5 years of age," said Carlier, an affiliated faculty member of the Virginia Tech Center for Freshmen Zoonotic Diseases and Arthropod Transmission Pathogens at Virginia Tech under the Flarin Institute of Life Sciences.

As early as 2016, with the National Institutes of Health (National Institutes of Health) funding for two years, the team had a scaffold, or basic chemical structure, and they carefully performed various chemical modifications to it.

From the original compound MMV008138, they created two promising new antimalarial drug candidates, or compounds that may become one drug, called PRC1584 and PRC1590

In order to understand malaria infection and how drugs fight against malaria, it is important to understand the extremely complex life cycle of the malaria parasite

But before this parasite attacks the human body, it first infects female Anopheles mosquitoes, the only mosquito species that can transmit malaria

When a human host is bitten by an infected mosquito, the initial number of parasites less than 100 will travel to the liver to reproduce and form their infantry

Then, like an enemy army occupying the battlefield, thousands of malaria parasites invade the blood and infect red blood cells (rbc)

In the blood, the parasite can also develop into a sexual form called the gamete cell stage

Carlier said: "If you have this kind of sexual behavior in your blood, and then you are bitten by a mosquito, this is the only life stage where you can continue to circulate and infect the mosquito

The ultimate goal is to create an anti-malaria drug with these properties and cure severe malaria with a single oral dose

To achieve these goals, Carly will continue his collaboration with Maria Belen Cassera, an associate professor of biochemistry and molecular biology and a faculty member of the Center for Tropical & Emerging Global Diseases, a computational chemist at the University of Georgia and Max Totrov Molsoft, a leading supplier of tools, structures Database and consulting services in proteomics, bioinformatics and rational drug design

After medicinal chemist Carlier prepares new variants of antimalarial lead compounds, these compounds will be sent to Cassera, which will test their antimalarial effects in various cells and animal models

The team is optimistic that their research will provide candidates for advanced preclinical evaluation, a process that may require collaboration with global health public-private partnerships
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The road to drug development may be long, but in the process there are often basic discoveries in disease biology
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Virginia Tech recently submitted patent applications for these two drug candidates and awarded the team a proof-of-concept award
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