In silico drug discovery: Unveiling potential targets in Plasmodium falciparum

Abstract

In silico drug discovery: Unveiling potential targets in Plasmodium falciparum R. Murugesan *, B. Kaleeswaran PG and Research Department of Zoology and Biotechnology, A Veeriya Vandayar Memorial Sri Pushpam College (Autonomous), Affiliated to Bharathidasan University, Poondi, Thanjavur, Tamil Nadu, India A R T I C L E I N F O Handling Editor: A Angelo Azzi Keywords: Drugs Phytochemicals Malaria Plasmodium Molecular dock A B S T R A C T Objective: Malaria, the plasmodium parasite, which causes and affects nearly half of the world’s population, is the biggest human health issue. Malaria results in an annual death toll ranging from 1.2 to 2.7 million worldwide. Consequently, there is a pressing need for novel active ingredients with targeted effects to curb the worldwide spread of malaria. Methods: This research is to explore innovative pharmacological molecules and employ bioinformatics methods (in silico) for the development of effective anti-malarial drugs. As part of the newest research into antimalarial chemicals, our study found seven drug combinations from different databases that showed drug-like properties and strong antimalarial activity in silico. Results: The hexokinase-1 protein (PDB: 1CZA) was docked with dioncophyllin-A, hugorosenone, marmesine, oxyprotostemonin, pachyrrhizin, plumbagin, and stemocurtisin. Among the pachyrrhizin compounds, the one with the highest docking score (􀀀 9.9 kcal/mol) was directed towards the 1CZA protein. Through superimposing the target and template structures, the active centres of the hexokinase I protein were identified, revealing structurally identical folds and undoubtedly conserved active sites. The SWISS-ADME tool was used to check how well the drug candidates were absorbed, distributed, broken down, and flushed out of the body (ADME). Conclusions: In summary, our research identifies pachyrrhizin as a as a potential anti-malarial drug combination with strong in silico activity. We’ve elucidated their interaction with the hexokinase-1 protein and assessed their favourable pharmacokinetic properties. These findings represent a significant step toward developing effective treatments for malaria, emphasizing the importance of further experimental validation and clinical studies.