Binding investigation of non-toxic compounds from plant-based repellents targeting Aedes aegypti odorant-binding protein 1 using molecular dynamics simulations and density functional theory

Abstract

Due to the effects of global warming, dengue and chikungunya virus infections have become significant global health concerns. Aedes aegypti is a known vector of these viruses. Based on the known mosquito repellents, there are many drawbacks and side effects in either human or environment. In this study, the disruption of the olfactory system targeting on Aedes aegypti odorant-binding protein 1 (AaegOBP1) by using the new candidates from nine plants which are known plant-based repellents was considered systematically by molecular dynamics simulations and density functional theory. Compounds with favorable pharmacokinetic profiles and no predicted adverse side effects were selected. Four selected compounds from holy basil (cpds 1–2), coriander (cpd 2), and ylang-ylang (cpds 3–4) were determined their binding affinity and binding stability with the structure of AaegOBP1 as compared to the known repellents, DEET and icaridin. All four compounds revealed the superior binding to AaegOBP1 than the known repellents because these selected compounds could occupy both binding site which can confirm by the binding free energy using MM-PBSA and MM-GBSA methods and interaction energy using density functional theory. In addition, the insight investigation also revealed the key interaction to Trp114 which was the similar key residue during the binding of DEET and icaridin. The obtained results revealed the binding patterns which can be helpful for the development of new potent mosquito repellents.