In silico antimalarial investigation of some bioactive molecules targeting Plasmodium falciparum’s Sortilin protein

SAJSET-01-2023-0022

Abstract

Plasmodium falciparum (P falciparum) is the most prevalent malaria parasite in Africa, accounting for 99.7% of estimated malaria cases in 2017. P falciparum Sortilin protein has a potential role as a protein escorter to the Rhoptry organelle. Rhoptry organelle is an essential protein for erythrocyte invasion by P falciparum. Hence, this study was aimed at identifying natural bioactive molecules from the natural product library (NPlib) of RPBS webserver through an in-silico approach that can inhibit P falciparum Sortilin protein from binding cargo proteins. Of the 652 ligands screened and docked from the NPlib, ten (10) ligands with the least binding energy scores were selected and their physiochemical and Absorption, distribution, metabolism, elimination and toxicity (ADMET) properties were checked using Swiss institute of bioinformatics webserver. Further molecular docking studies carried out revealed that lutein and β-carotene were the most potent inhibitors of P falciparum Sortilin protein with binding affinities of -20.9 kcal/mol and -18.9 kcal/mol, respectively. The findings of this study are believed to serve as a baseline information for further wet lab investigations by pharmaceutical organizations toward the development of new drugs for combating the endemicity of malaria in this region of the globe.