Virtual screening and experimental validation of inhibitors of Plasmodium spp. casein kinases, CK1 and CK2α, as potential antimalarial candidates

Worldwide, malaria affected 219 million people in 20171. Currently, for control and eradication, while trying to avoid parasite resistance emergence, combination therapy is needed. Thus, it becomes urgent the discovery of new antimalarials with different mechanisms of action. Here, we describe an integrated computational and experimental approach to select new promising antimalarial candidates. Through bioinformatics, we selected casein kinases proteins (CK1 and CK2α) of Plasmodium spp. as potential targets2-3. The 3D-structures were obtained from crystallographic structure (PfCK2α) and by homology modeling (PvCK1). We selected compounds from DIVERSet EXP from ChemBridge library, performed sequential dockings using different precision modes, related to different scoring function acuracy, and sampling using Glide software. We predicted the activity of hits through our in house QSAR model for P. falciparum, resulting in 207 hits. Now, we are performing the experimental validation of 196 available compounds against asexual blood stage of P. falciparum.