Exploring potential of Plasmodium RUVBL proteins as anti-malarial drug target

Abstract

Although malaria related cases and deaths have consistently declined over time, growing resistance to existing anti-malarial drugs in Plasmodium remains a matter of extreme concern. Since we rely so heavily on use of chemotherapy for malaria treatment and knowing that all the available anti-malarial drug will become virtually useless in the near future, we have to increase our understanding of basic biology of the parasite as well as characterize new molecular targets that can be exploited for anti-malarial therapy. In the present study, PfRUVBLs (AAA family member proteins) were evaluated for their potential as novel anti-malarial drug target candidates, using computational approaches. Virtual High-throughput screening of various pharmacophore libraries obtained from three different databases (which included, Asinex, ZINC15 & PubChem) followed by extra precision docking, resulted in identification of relevant hit compounds that showed binding affinity with the active region of PfRUVBL1 protein. Based on molecular docking data, MD simulations, and protein-ligand interaction studies, combined with toxicity assessment & ADME profiling data, at least three best hits were eventually identified that could be novel potent inhibitors of PfRUVBL1 protein and can be further tested for anti-malarial activity using in vitro protocols. Communicated by Ramaswamy H. Sarma