In Silico Studies of the Interactions of Chitin-Based Compounds and AeHKT Enzyme for the Development of Dengue Larvicides

Waste shells from the seafood industry pose a significant environmental challenge due to their abundance. However, these shells are a valuable source of chitin, a polysaccharide that can be extracted and converted into chitosan. Chitosan has gained attention for its diverse applications, including its potential as a larvicide against Aedes aegypti mosquitoes. With dengue fever continuing to be a major public health threat, there is a pressing need for safer and more effective larvicides. This study investigates the potential of chitin-derived compounds as larvicides through in silico methods, focusing on their interaction with the Alanine Glyoxylate Aminotransferase (AeHKT) enzyme. The primary aim of this research is to evaluate the efficacy of chitin-based compounds as larvicides against A. aegypti via computational approaches. The study follows three main steps: ligand-based screening, solubility prediction, and structure-based screening using molecular docking. Initially, 500 compounds were retrieved from the ChEMBL database using the Rchemcpp web-based application. These compounds were ranked based on their similarity to N-Acetyl-beta-D-glucosamine, a chitin derivative, and the top ten were selected for further analysis. Among these, 2,4,6-tris(methylsulfanyl)pyrimidine emerged as the most promising compound, with a 98.28% structural similarity to N-Acetyl-beta-D-glucosamine, high solubility (greater than 0.06 mg/mL), and a favourable logP value (-2.58). Docking studies using AutoDock4 revealed a strong binding affinity (-5.17 kcal/mol) and low torsional energy (1.49 kcal/mol) of this compound when interacting with AeHKT, indicating its potential as an environmentally friendly larvicide. This study lays the groundwork for the development of new, environmentally sustainable larvicides for the control of dengue vectors, offering a promising approach to combat the spread of dengue fever.