MMV malaria box phenotyped against plasmodium and toxoplasma

A Singapore-India collaborative research project has completed phenotypic screening of MMV Malaria Box, a large collection of potent chemical inhibitors against pathogenic parasites Toxoplasma gondii and Plasmodium falciparum, the causative agents of human toxoplasmosis and malaria. This research opens up new avenues to study unique stages of the infectious cycle that are affected by inhibitor classes toward anti-parasitic drug development.

Plasmodium parasites cause malaria and morbidly impact the economies of the developing world. Although, asymptomatic and not as deadly as malaria, toxoplasmosis can lead to serious health concerns in pregnant women (and in immuno-compromised individuals). Towards reducing the global burden of malaria and other neglected diseases, millions of compounds were screened, prioritized and assembled by the WHO-supported Medicines for Malaria Venture (MMV) as the MMV ‘Malaria Box’ collection of 400 chemically diverse small . However, how these inhibitors kill the parasites remain largely unknown. Through complementary and comparative screening, the SUTD-NCL team has now discovered and segregated the MMV box library based on the life-stage events affected by individual inhibitors.

The team used complementary phenotypic screens on P. falciparum and T. gondii to identify phenotype-specific hits based on:

  • Inhibition of overall parasite growth,
  • Apicoplast segregation, and
  • Egress or host invasion and cross-validated between the two related, yet distinct parasitic forms.

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