Drug candidates identified for the prevention of malarial parasite maturation

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A team of researchers from Imperial College London (UK) have identified compounds which prevent the malarial parasite sexually maturing inside the mosquito.

Results published in Nature Communications indicate that six out of 70,000 screened compounds were identified as potential drug candidates for blocking transmission of the disease.

“Current antimalarial drugs can cure a person of the disease, but that person is still infectious to mosquitoes, and can therefore still cause someone else to become infected,” explained Professor Jake Baum (Imperial College London).

“What we propose is antimalarial drugs that protect mosquitoes, blocking the parasites from continuing their infectious journey. By combining such a drug with a conventional antimalarial, we not only cure the individual person, but protect the community as well.

“At the level of the individual person, fighting malaria is a constant battle as parasites become resistant to antimalarial drugs. Since transmission occurs in the mosquito, drugs targeting this process have the added benefit of being naturally much more resistance-proof, which could be essential for eliminating malaria.”

Sexual parasites are extremely active inside the mosquito and are one if the fastest replicating cell types known. They are therefore strong candidates for drug targets.

By mimicking the conditions inside mosquitoes, the parasites were fooled into started sexual development. The process was then refined and miniaturized to allow examination by microscope, and the screening of thousands of compounds.

The team claims that one compound has already been tested successfully and blocked parasite transmission in mice, but further research is required to investigate the remaining five compounds and how they may be adapted for future pharmaceutical use.

“It took several years to find the right conditions that would stimulate the sexual parasites and to miniaturize the environment, but it was worth it – at our best we were screening 14,000 compounds a week,” Baum added.

“Overall we screened around 70,000 molecules and found only a handful of potent compounds that are both active and safe to use with human cells. It was like finding needles in a haystack.”

Sources: Delves MJ, Miguel-Blanco C, Matthews H et al. A high throughput screen for next-generation leads targeting malaria parasite transmission. Nat. Commun. 9(3805) (2018); www.eurekalert.org/pub_releases/2018-09/icl-dts091718.php

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