Abstract
Dengue fever is caused by Flaviviridae viruses and transmitted mainly by Aedes aegypti; there are about 390 million cases of dengue fever annually, the majority in tropical countries. Increased resistance to insecticides in this vector has reduced the effectiveness of traditional control measures and led to the need for more sustainable alternative control measures using plants. This study aimed to assess the ability of Melaleuca cajuputi (cajuput/gelam) essential oil (MCEO) to interfere with the host-seeking behaviour of Ae. aegypti by targeting odorant-binding proteins (OdBPs) using a computational approach. 63 OdBP sequences were retrieved from GenBank and homology modeling was done using Swiss-Model, and six MCEO bioactive compounds were retrieved from PubChem and converted from SDF to PDB format using Open Babel GUI. AutoDock Vina was used to evaluate OdBP ligand interactions via molecular docking. After modelling and validation, 14 OdBPs were chosen for analysis for structural reliability, the GMQE values ranged from 0.75-0.89, and more than 85% of the residues were in favoured Ramachandran regions. When docking, strong ligand protein interactions were observed, with OdBP17 having the highest binding affinity for γ-terpinene (−7.4 kcal/mol), interacting with the key residues Leu84, Leu118, Leu129, Phe22, Val68, and Val80. Other significant interactions were found between OdBP39 carene and OdBP27 p-cymene. The values of −6.90 kcal/mol and −8.83 kcal/mol binding affinities to OdBP17 with reference ligands DEET and N-phenyl-1-naphthylamine (NPN), respectively, validated the docking approach in this study. The results show that MCEO compounds can bind with strong affinities to the Ae. aegypti OdBPs and can form stable complexes that are potentially functional, which make them promising candidates for natural olfactory disruptors for sustainable control of the dengue vectors.
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