Frontiers in Tropical Diseases · Published 2026-07-29 · DOI 10.3389/fitd.2026.1882408
Rohit Lakhwani, Kajal Narwal, Sanskriti Ojha, Shreya Jha, Roopa Rani Samal, Sarita Kumar
IntroductionAedes aegypti serves as a primary vector for several arboviral diseases. The emergence of Aedes-borne diseases has raised concerns in health sectors worldwide. Despite the efficacy of synthetic insecticides, their repeated and random use in the fields has made mosquitoes resistant, reducing their effectiveness in control programs and causing environmental hazards. Hence, the present study aimed to assess the baseline susceptibility of α-cypermethrin to Ae. aegypti and understand the involvement of detoxification enzymes in its defense system.MethodsThe study evaluated the susceptibility of Ae. aegypti to α-cypermethrin using the WHO bottle bioassay and investigated the enzymes involved in metabolic resistance through molecular docking and biochemical estimation. Adult females were exposed to different concentrations of α-cypermethrin using the WHO bottle bioassay to assess their susceptibility status. The effect was estimated on five detoxification enzymes, namely, glutathione-S-transferase (GST), cytochrome P450 monooxygenase (CYP450), α-esterase, β-esterase, and acetylcholinesterase (AChE), through molecular docking and biochemical assays.ResultsThe LC50 and LC90 values of α-cypermethrin were 0.00007% and 0.00059%, respectively. Exposure to the diagnostic dose (10 µg/bottle) caused 97.91% mortality, indicating suspected early signs of insecticide resistance development, according to WHO guidelines. Docking analysis showed the strongest binding affinity of β-esterase with α-cypermethrin (−9.4 kcal/mol), followed by CYP450 (−8.8 kcal/mol), GST (–7.5 kcal/mol), α-esterases (−7.1 kcal/mol), and AChE (–6.6 kcal/mol), suggesting their variable but significant involvement in detoxification. These results were corroborated by biochemical estimation of the enzymes, revealing an increase in the levels of all detoxification enzymes except GST, which showed decreased levels. The maximum effect was recorded on β-esterase levels, resulting in a 21.41-fold increase in activity.ConclusionThe present study shows the significant impact of α-cypermethrin on the survival and detoxification enzymes of Ae. aegypti. The molecular docking and biochemical characterization of detoxification enzymes demonstrated the major role of β-esterase, while also indicating a significant contribution of other enzymes to the activation of the defense system of Ae. aegypti. This is the first report that unravels the effects of α-cypermethrin on the detoxification enzymes of Ae. aegypti through molecular docking validated by biochemical assays. The study improves our understanding of resistance mechanisms and highlights the importance of regular resistance monitoring for effective mosquito control.
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Lakhwani, R., Narwal, K., Ojha, S., et al. (2026). Molecular docking analysis and biochemical characterization of metabolic detoxification enzymes in adults of Aedes aegypti L. (Diptera: Culicidae) exposed to α-cypermethrin. Frontiers in Tropical Diseases. https://doi.org/10.3389/fitd.2026.1882408