Identification of Malaria-Selective Proteasome β5 Inhibitors Through Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation.

ABSTRACT: Malaria remains a global health challenge, with increasing resistance to frontline antimalarial treatments such as artemisinin (ART) threatening the efficacy of current therapies. In this study, we investigated the potential of FDA-approved drugs to selectively inhibit the malarial proteasome, a novel target for antimalarial drug development. By leveraging pharmacophore modeling, molecular docking, molecular dynamics (MD) simulations, and binding free-energy calculations, we screened a library of compounds to identify inhibitors selective for the Plasmodium proteasome over the human proteasome. Our results highlighted Argatroban, LM-3632, Atazanavir Sulfate, and Pemetrexed Hydrate as promising candidates, with Argatroban and Pemetrexed Hydrate showing the highest binding affinity and selec

SUBMITTER: Yasir M 

PROVIDER: S-EPMC11593624 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature