Targeting Aedes aegypti Metabolism with Next-Generation Insecticides

Abstract

Aedes aegypti is the primary vector of dengue virus (DENV), zika virus (ZIKV), and other emerging infectious diseases of concern. A key disease mitigation strategy is vector control, which relies heavily on the use of insecticides. The development of insecticide resistance poses a major threat to public health worldwide. Unfortunately, there is a limited number of chemical compounds available for vector control, and these chemicals can have off-target effects that harm invertebrate and vertebrate species. Fundamental basic science research is needed to identify novel molecular targets that can be exploited for vector control. Next-generation insecticides will have unique mechanisms of action that can be used in combination to limit selection of insecticide resistance. Further, molecular targets will be species-specific and limit off-target effects. Studies have shown that mosquitoes rely on key nutrients during multiple life cycle stages. Targeting metabolic pathways is a promising direction that can deprive mosquitoes of nutrition and interfere with development. Metabolic pathways are also important for the virus life cycle. Here, we review studies that reveal the importance of dietary and stored nutrients during mosquito development and infection and suggest strategies to identify next-generation insecticides with a focus on trehalase inhibitors.

Implications of mosquito metabolism on vector competence

“…, 2016; Conway et al. , 2023). Recent studies have provided valuable insights into how arboviruses selectively affect the metabolic pathways of mosquito vectors (Colpitts et al.…”

“…Flaviviruses, including DENV, ZIKV, JEV, and WNV, are intracellular pathogens that rely on the host's metabolism to produce offspring virions, similar to Plasmodium parasites (Liu et al, 2016;Conway et al, 2023). Recent studies have provided valuable insights into how arboviruses selectively affect the metabolic pathways of mosquito vectors (Colpitts et al, 2011;Chotiwan et al, 2018;Siriphanitchakorn et al, 2022).…”

In Silico Larvicidal Activity Study of Six Limonoids Against Mosquito Larvae (Aedes aegypti L.) Ecdysone Receptor Protein

“…A number of antimosquito insecticides currently in use present disadvantages such as toxicity to humans and other non-target species, degradation of the aquatic environment, high annual costs, and the development of target-resistant population (4). To mitigate these challenges, efficient and cost effective approaches are required to identify innovative mosquito control strategies in addition to developing new insecticides that overcome the adverse problems associated with insecticides currently in use (5). Efforts by researchers to develop new environmentally friendly insecticidal compounds against mosquitos, have yielded various compounds both synthetic and naturally occurring with potential larvicidal activity against various mosquito species (6)(7)(8)(9).…”

“…In the present work, the limonoids, pyroangolensolide synthesized by reducted calodendrolide (pyroangolensolide), calodendrolide, limonin, and limonin diosphenol from Calodendrum capensi, while harrisonin and pedonin from Harrisonia abyssinica (Figure 1) reported earlier as potential mosquito larvicides were subjected to an in silico study involving the docking of the six limonoids (1)(2)(3)(4)(5)(6) in the Ecdysone Receptor (EcR) protein 1z5x-Ligand Binding Pocket (LBP) (16,17). This was compared with the binding affinity displayed by the dipteran specific ecdysone agonist, RH 5849 (1,2-Dibenzoyl-1-tertbutylhydrazine).…”