Medicinal plants are nature’s gifts that offer diverse therapeutic effects. Although numerous plants and plant-derived products have been investigated for potential anti-malarial effects, the challenge of drug resistance necessitates the continuous search for more effective and sensitive antimalarial drug candidates. Thus, this study uses molecular docking and dynamic simulation approaches to bioprospect compounds with potential to interact with Plasmodium falciparum lactate dehydrogenase (PfLDH). In silico mutagenesis was used to comparatively analysis the anti-resistant malaria potential of the hit compounds against mutated PfLDH. A total of 24,316 compounds were retrieved from reputable Traditional Chinese Medicine (TCM) compound repositories, screened, and systematically analyzed for binding interaction and stability with the PfLDH. The identified top-three compounds; ZINC70450989, ZINC85506851, and ZINC85506187 exhibited appreciable binding interaction and stability with the target relative to the standard reference drugs with binding free energies of -91.63, -60.55, and -58.66 kcal/mol, respectively compare to (-36.59 kcal/mol) for artemisinin and piperaquine (-48.57 kcal/mol) in silico. The top three compounds maintained high binding energy and stable interactions, even in the presence of enzyme mutations. Pharmacokinetic and toxicity screening show that the top-ranked compounds possess good ADMET properties for druggability compounds. This study identifies natural compounds capable of interacting with and inhibiting PfLDH activity, highlighting their prospect as candidates for further drug development. Further in vitro and in vivo studies are recommended to validate their anti-malarial potentials.
Ibrahim et al. (Wed,) studied this question.