Rebecca C S Edgar, Tess R Malcolm, Ghizal Siddiqui, Carlo Giannangelo, Natalie A Counihan, Matthew Challis, Sandra Duffy, Mrittika Chowdhury, Jutta Marfurt, Madeline Dans, Grennady Wirjanata, Rintis Noviyanti, Kajal Daware, Chathura D Suraweera, Ric N Price, Sergio Wittlin, Vicky M Avery, Nyssa Drinkwater, Susan A Charman, Darren J Creek, Tania F de Koning-Ward, Peter J Scammells, Sheena McGowan
To combat the global burden of malaria, development of new drugs to replace or complement current therapies is urgently required. Here, we show that the compound MMV1557817 is a selective, nanomolar inhibitor of both Plasmodium falciparum and Plasmodium vivax aminopeptidases M1 and M17, leading to inhibition of end-stage hemoglobin digestion in asexual parasites. MMV1557817 can kill sexual-stage P. falciparum , is active against murine malaria, and does not show any shift in activity against a panel of parasites resistant to other antimalarials...
May 8, 2024: MBio