Computational identification of microbial metabolites as potential inhibitors of mosquito juvenile hormone binding protein for vector control

A group of acyclic sesquiterpenoids, that form the Juvenile hormone is crucial in the developmental physiology of insects. Aedes aegypti is crucial in spreading fatal diseases such as dengue, and dengue hemorrhagic fever. The mosquito undergoes several stages of development, from the egg to the adult stage, utilizing its innate immunity system and juvenile hormone proteins. Thus, targeting the juvenile hormone-binding proteins can potentially inhibit the developmental stages of the mosquito. The mosquito juvenile hormone binding protein (mJHBP) of Aedes aegypti was obtained from the RCSB (PDB). The study identified that Talaromyces islandicus and Bacillus velezensis produced secondary metabolites that act as efficient ligand complexes. The secondary metabolites were procured from PubChem and docked to the binding sites of mJHBP. Among the 26 listed ligand compounds, oxalic acid, decyl 3,5-difluorophenyl ester, oxalic acid 3,5-difluorophenyl undecyl ester, and p-octylacetophenone were found to have higher binding affinity, marking their efficiency in inhibiting the protein. Normal mode analysis studies were performed using iMODs to analyze the B-factor, variance, covariance, and Eigenvalues of the docked protein-ligand complexes. The Absorption, Distribution, Metabolism and Excretion (ADME) properties of the efficient ligand molecules were analyzed using the Swiss ADME tool to segregate potential drug candidates. Targeting the mJHBP complex using the microbial metabolite ligand molecules can inhibit the development of the mosquitoes. The work enlightens the futuristic development of potential candidates in the production of insecticides. The literature confirms it is the first of its type to utilize microbial bio compounds as ligands targeting the mJHB protein complex.