Identification of Promising Inhibitors from Natural Compounds Targeting PlmX, a Multi-Stage Drug Target in Plasmodium Falciparum
Author(s): Cheickna CISSE, Oudou DIABATE, Mamadou WELE, Mamadou SANGARE, Alia BENKAHLA, Jeffrey SHAFFER, Seydou DOUMBIA, Mamadou WELE
The emergence of resistance to the first-line antimalarial drugs poses a significant threat to recent progress in the fight against malaria. It is imperative to discover novel therapeutic drugs for Malaria. Utilizing rational methods facilitated by bioinformatics tools presents the most efficient and cost-effective approach to achieve this imperative. The objective of this study was: first, to model an active structure of Plasmepsin X (PlmX) a potent multistage drug target from Plasmodium falciparum, and second, to identify potential inhibitors from African databases of Natural Products. The model was constructed utilizing a multiple templates approach implemented in Modeller. The best model obtained underwent validation using standard tools. Subsequently, a high throughput virtual screening was conducted using Autodock Vina, employing African databases of Natural Products. The results demonstrated the successful construction of an accurate and validated model of PlmX. A total of 8690 compounds sourced from natural active compounds were screened, leading to the identification of 68 compounds exhibiting high affinity (docking score ≤ -9 kcal/mol). Further analysis revealed detailed interactions of top ten promising inhibitors, highlighting their potential as effective inhibitors. This study identified promising inhibitors to be considered in the development of new and effective antimalarial drugs.