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New compound can inhibit malaria parasite growth: Study

The researchers mentioned that the compound is now only a potential drug.

malaria parasite growth, indianexpress, indianexpress.com, parasite plasmodium, lifecycle, plasmodium, research, The study also noted that the compound was effective against other species of Plasmodium. (Source: Getty Images/Thinkstock)

An international team of researchers have found that a novel compound can halt the growth of the parasite Plasmodium falciparum known to cause malaria — the deadly mosquito-borne disease which kills nearly 500,000 people every year across the world. The study, published in the journal Science, noted that the compound called TCMDC-135051 developed by the multinational pharmaceutical company GlaxoSmithKline can eliminate the mosquito-borne parasite in all the stages of its lifecycle.

The researchers, including those from Brazil’s Sao Paulo Research Foundation (FAPESP), noted that the drug specifically acted on a protein in the the parasite called the cyclin-dependent-like protein kinase — PfCLK3 — without affecting human proteins.

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The researchers noted that PfCLK3 controlled the activity and production of other proteins required by the parasite to stay alive, and by blocking these, killed P falciparum.

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According to the study, inhibition of PfCLK3 not only affected the parasite’s asexual stage of development — when it proliferated in human cells, and caused symptoms — but also in the sexual stage, when it can be transmitted back to mosquitoes, repeating the cycle by infecting other humans.

To identify compounds that specifically inactivated the PfCLK3 protein, the researchers conducted a large scale automated chemical analysis — through a process called high-throughput screening.

In the process, they analysed nearly 25,000 compounds, and selected TCMDC-135051 since it showed the most exclusiveness in binding with the parasite’s protein, and had high potency in this regard.


The study also noted that the compound was effective against other species of Plasmodium.

“We also tested it in mice infected with Plasmodium berghei. The results of this in vivo trial showed that the parasite was eliminated from the bloodstream after five days of infection,” said Paulo Godoi, co-author of the study from University of Campinas in Brazil.

Since both the parasite and humans have proteins similar to PfCLK3 orchestrating the activity of almost all processes in cells, the researchers performed experiments to confirm that TCMDC-135051 was safe, and did not act on the human forms of the protein.


The researchers found that the human protein that most closely resembled the parasite’s PfCLK3 was the protein named PRPF4B.

“We had PRPF4B interact with the new molecule at different concentrations, and it proved unable to inhibit the human kinase even at the highest concentration,” Godoi said.

The researchers mentioned that the compound is now only a potential drug, and will have to be submitted to more tests to prove that it can be used clinically.

“We need to improve the molecule’s safety even more. Then, it will be ready for trials in humans. That stage will take between three and five years,” said Andrew Tobin, lead author of the study from the University of Glasgow in the UK.

First published on: 08-10-2019 at 13:14 IST
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