Investigation of Averrhoa bilimbi fruit extract-derived compounds as potential acetylcholinesterase inhibitors in Aedes aegypti: Insights from molecular docking and molecular dynamics simulations

Abstract

Aedes mosquitoes are primary vectors of human diseases such as dengue fever, chikungunya, and yellow fever. Their control heavily depends on chemical insecticides, but the rise of resistance in Aedes aegypti populations presents a significant challenge. This study explores the potential of bioactive compounds from Averrhoa bilimbi (starfruit) fruit as acetylcholinesterase (AChE) inhibitors for mosquito control. A total of 20 active compounds from A. bilimbi fruit extracts were identified using Gas Chromatography-Mass Spectrometry (GC-MS) and subjected to molecular docking analysis to evaluate their binding affinity toward AChE. Molecular dynamics (MD) simulations using YASARA software further assessed their stability and interaction dynamics. Among these compounds, ß-Amyrin (-9.4 kcal/mol) and Urs-12-ene (-9.3 kcal/mol) exhibited the strongest binding affinities, surpassing the reference inhibitor donepezil (-8.3 kcal/mol). However, MD simulations revealed that Urs-12-ene exhibited unstable binding and conformational fluctuations, making ß-Amyrin the most promising AChE inhibitor. This compound demonstrated strong and stable interactions with AChE, as supported by binding affinity, binding site analysis, and interaction stability. These findings suggest that ß-Amyrin from A. bilimbi fruit extracts holds promise as a natural AChE inhibitor for mosquito control. However, further in vitro and in vivo studies are necessary to validate its inhibitory potential and assess its efficacy and safety for practical application.