After a long, long wait – the work was initially published on the pre-print server bioRxiv in January 2018 – yesterday saw the official release of our work on a new class of potent anti-malarials, the pantothenamides. In a large public-private and transatlantic collaboration, bringing together cutting-edge synthetic and biochemistry, metabolomics, and genetic engineering, we have developed compounds that target asexual and sexual blood-stage parasites. Using CRISPR-Cas9-based approaches, my PhD student Laura de Vries has provided compelling evidence approaching a mechanism of action. Our data suggest that drug-derived CoA analogues act as antimetabolites that target acetyl-CoA synthetase thereby inhibiting the conversion of CoA to acetyl-CoA. This work also featured key contributions during the revision stages by Julie Verhoef, who worked with Laura as a master intern and was awarded a well-deserved second authorship for her efforts. Our current studies are focussing on drug resistance profiles and the mechanism of action of these pantothenamides during transmission.
Congratulations to Laura for her first chapter for het PhD thesis, to Julie for her very first paper, and to the entire team for completing this tremendous effort!
Image designed by Laura de Vries.
Taco Kooij 