Researchers at the Broad Institute of MIT and Harvard have discovered compounds with potential to prevent the transmission of malaria.
The new compounds act on a novel target in the malaria parasite, Plasmodium falciparum, and have been identified after screening a library of more than 100,000 small molecules.
Broad’s Centre for the Development of Therapeutics (CDoT) senior research scientist Nobutaka Kato said: “This compound targets all vertebrate stages of the P. falciparum malaria infection.
“The parasite goes to the liver first, then the bloodstream, followed by a transmission stage. Our compound hits all three of these stages, which is very rare in the therapeutic pipeline.”
A team of researchers led by Stuart Schreiber, director of the Centre for the Science of Therapeutics (CSofT), screened CSofT’s full diversity oriented synthesis (DOS) library of small molecular compounds against P. falciparum parasites.
The DOS comprises a collection of chemical compounds that are not traditionally represented in pharmaceutical libraries and were designed to emulate small molecules found in nature.
Scientists have prioritised certain DOS compounds for further study that showed signs of operating through a novel mechanism of action during initial screens.
The team looked for compounds that could work in all three stages of the P. falciparum life cycle.
When tested in mice, these compounds eradicated the malaria parasites during all three stages of the disease.
The compounds they found act on phenylalanyl-tRNA synthetase, a complex enzyme that contributes to protein synthesis and could potentially wipe out parasites before they fester in the liver and are released into the blood.
Image: Screens of the Broad’s entire DOS library identified compounds that act on a novel malaria target during all three stages of the disease. Photo: courtesy of Susanna Hamilton, Broad Communications.