In silico screening for safe and potent essential oils against mosquito neural targets

Abstract Background Mosquito-borne diseases remain a major global health challenge, highlighting the need for eco-friendly alternatives to conventional chemical insecticides. This study aimed to evaluate a tiered in silico screening framework to prioritize plant-derived essential oils as potential sustainable mosquito control agents. Results A large-scale virtual screening of 5,183 essential oils was conducted, followed by toxicity-based filtering, yielding 1,345 low-toxicity candidates. Subsequent molecular docking against neural targets of Culex pipiens identified 51 top-priority oils. Among these, German chamomile ( Matricaria chamomilla ) consistently appeared across multiple chemotypes. The Egyptian German chamomile essential oil was selected for experimental validation. Chemical analysis revealed sesquiterpenes, particularly bisabolol oxide derivatives and β-farnesene, as major constituents. Docking results demonstrated strong binding affinities toward multiple neural targets. Larvicidal bioassays showed 100% mortality at 400 ppm after 24 h, accompanied by significant behavioral, morphological,and histopathological abnormalities. Neurochemical assays indicated increased acetylcholinesterase activity, alongside decreased γ-aminobutyric acid levels, suggesting disruption of neural signaling. Conclusions This study demonstrates the effectiveness of in silico screening in identifying safe and potent plant-based mosquito control agents. German chamomile essential oil emerges as a promising eco-friendly candidate for sustainable vector management, warranting further field-based validation.