Insecticide discovery by drug repurposing: new synergistic inhibitors against Periplaneta americana

Abstract

Virtual screening (VS) procedures have been widely used to accelerate the drug discovery process. These procedures have also been implemented in other fields such as catalysts, energetic materials and more recently, the design of novel insecticides. The latter is an industrial priority to meet current legislation. Particularly challenging are cockroaches as they are associated with a number of diseases, while the available solutions are harmful to humans. Herein, we performed an in silico and in vivo screening of the Drug Bank (DB) database for new potential voltage-dependent sodium channel (VGSC) synergists against the American cockroach (Periplaneta americana). The VS pipeline procedure implements two ligand-based methods, e.g., Glide and METADOCK 2.0, which are further refined by rescoring. The most promising compounds are tested using in vivo models. Our combined computational and theoretical scheme leads to the discovery of miglitol as a new effective synergistic compound when combined with commercial formulations. Miglitol speeds up the overall knockout time by a factor of 12× while providing 100% of mortality after 24 hours. These findings open the door to improved insecticides as well as to a wider use of VS methods.