Multi-stage insecticide potentials of Myristica fragrans against the invasive Aedes albopictus, and putative binding mechanism of myristicin targeting the odorant-binding proteins (OBPs)
The Asian tiger mosquito, Aedes albopictus, is native to Southeast Asia and an invasive species with rapid geographical expansion. Aedes albopictus has contributed to the spread of numerous infectious diseases affecting both humans and animals. This study evaluated the insecticidal potential of Myristica fragrans essential oil (MFEO) from Maluku Island against multiple life stages of Ae. albopictus. MFEO completely inhibited egg hatching from 0.001% (w/v), with treated eggs remaining unhatched throughout a 25-day observation period; scanning electron microscopy revealed structural damage to the exochorionic layer, indicating that disruption of the egg surface impairs embryonic development. In larvicidal assays, MFEO showed rapid, concentration- and time-dependent toxicity, achieving 100% mortality within 30 min at concentrations of 100 ppm and above, comparable to temephos; at 1–50 ppm, complete lethality was reached within 120 min. Against adults, MFEO produced a 30-min knockdown concentration (KD50) of 1.545% and a 24-h lethal concentration (LC50) of 0.270%. MFEO-treated ovitraps received no eggs, whereas controls attracted 78–90 eggs in 48 h. Gas chromatography-mass spectrometry identified myristicin (35.35%) as the principal constituent, with α-terpineol comprising 10.74% and phenol, 2,4,6-tris(1-phenylethyl)- comprising 11.24%. Molecular docking against 19 annotated odorant-binding proteins (OBPs) of Ae. albopictus showed the strongest binding of myristicin to OBP3 (−6.8 kcal/mol), mediated by van der Waals, hydrophobic and polar hydrogen interactions; molecular dynamics validation (CABS-flex) of the myristicin-OBP3 complex yielded a mean root-mean-square fluctuation of 1.468 Å, i.e. below the 2 Å stability threshold. Further docking against acetylcholinesterase (AChE), GABA receptors and voltage-gated sodium channels (VGSC) supported a neurotoxic component. Together, these results indicate that MFEO disrupts multiple life stages through combined chemosensory interference, eggshell damage and neurotoxic action. The multi-target, multi-stage activity observed in MFEO, together with its behavioral deterrent effects, suggests it warrants further investigation as a botanical candidate for integrated vector management, potentially offering an alternative to some conventional neurotoxic insecticides. Further, functional validation by bio-guided fractionation and target-specific assays is recommended.