Fragment-based virtual screening discovers potential new Plasmodium PI4KIIIβ ligands.

ABSTRACT: Type III beta phosphatidylinositol 4-kinase (PI4KIIIβ) is the only clinically validated drug target in Plasmodium kinases and therefore a critical target in developing novel drugs for malaria. Current PI4KIIIβ inhibitors have solubility and off-target problems. Here we set out to identify new Plasmodium PI4K ligands that could serve as leads for the development of new antimalarial drugs by building a PPI4K homology model since there was no available three-dimensional structure of PfPI4K and virtually screened a small library of ~ 22 000 fragments against it. Sixteen compounds from the fragment-based virtual screening (FBVS) were selected based on ≤ - 9.0 kcal/mol binding free energy cut-off value. These were subjected to similarity and sub-structure searching after they had passed PAINS sc

SUBMITTER: Ibezim A 

PROVIDER: S-EPMC8944149 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature