Three major pyrethroid resistance mechanisms. (A) At the target site, pyrethroid molecules (gold spheres) bind voltage-gated sodium channel (VGSC) (aqua) to depolarize motoneurons and cause paralysis. Target site mutations were subsequently selected in resistant populations. (B) Biochemical effectors detoxify pyrethroids to nontoxic forms, e.g., phenoxybenzoic acid (PBAc), that are excreted (Figure 2). Pyrethroid is indicated in gold spheres; cytochrome P450 (CYP) proteins are indicated in green; carboxylesterases (COEs) are indicated in pink; rejuvenation of CYP (from blue oxidized to reduced green form) by nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome P450-reductase (CPR) [45]. (C) Cuticular thickening and/or modifications are also features of resistance. Figure prepared using Biorender, with permission (Biorender.com, accessed on 22 March 2021). Chemical structures were drawn using Marvin JS (v. 17.4.3, chemaxon.com, accessed on 22 March 2021).