AUTHOR=Salifu Elliasu Y. , Abugri James , Rashid Issahaku A. , Osei Festus , Ayariga Joseph Atia 

TITLE=In silico identification of potential inhibitors of acyl carrier protein reductase and acetyl CoA carboxylase of Plasmodium falciparum in antimalarial therapy

JOURNAL=Frontiers in Drug Discovery

VOLUME=Volume 3 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/drug-discovery/articles/10.3389/fddsv.2023.1087008

DOI=10.3389/fddsv.2023.1087008

ISSN=2674-0338

ABSTRACT=Malaria caused by Plasmodium falciparum remains one of the fatal parasitic diseases that has affected nearly a third of the world's population. The major impediment to the treatment of malaria is the emergence of resistance of the P. falciparum parasite to current anti-malarial therapeutics such as Artemisinin (ART)-based combination therapy (ACT). This has resulted in countless efforts to develop novel therapeutics that will counter this resistance with the aim of controlling and eradicating the disease. The application of in silico modelling techniques has gained a lot of recognition in antimalarial drug research in recent times. Key biological components of the parasite have been targeted for rational drug design leveraging in silico applications. In this study various in silico techniques such as Virtual screening, molecular docking, and molecular dynamic simulations were employed to identify potential new inhibitors of biotin acetyl-coenzyme A (CoA) carboxylase and enoyl-acyl carrier protein reductase, two enzyme targets that play a crucial role in fatty acid synthesis in the Plasmodium parasite. Initially, 9 hit compounds were identified for each of the two enzymes from the ZincPharmer database. Subsequently, all hit compounds bound favourably to the two enzymes' active sites and showed excellent pharmacokinetic properties. Three (3) of the hits for the biotin acetyl-coenzyme A (CoA) carboxylase and six (6) of the enoyl-acyl carrier protein reductase showed good toxicity properties. The compounds were further evaluated based on the Molecular Dynamics (MD) simulation that confirmed the binding stability of the compounds to the targeted proteins. Overall, the lead compounds Zinc38980461, Zinc05378039, and Zinc15772056, were identified for acetyl-coenzyme A (CoA) carboxylase whiles zinc94085628, zinc93656835, zinc94080670, zinc1774609, zinc94821232, and Zinc94919772 were identified as lead compounds for enoyl-acyl carrier protein reductase. The identified compounds could be developed as a treatment option for malaria disease although, experimental validation is suggested for further evaluation of the work.