Computational Discovery of NPA001937: A Novel Carotenoid Targeting Conserved Insect Proteins for Sustainable Pest Management.

The emergence of insecticide resistance in pests affecting cotton and other key crops presents an escalating challenge to global agriculture, resulting in considerable declines in both yield and quality. Resistance mechanisms, including target site mutations and improved detoxification processes, have diminished the effectiveness of traditional insecticides. This study identified NPA001937 (di-O-demethylspirilloxanthin), a bacterial carotenoid obtained from the Natural Products Atlas, as a promising natural insecticidal compound. Employing in silico methods, we focused on three essential insect targets: Ryanodine Receptor (RyR), Arginine Kinase (ArgK), and Serine/Threonine Protein Phosphatase (STPP), which are known for their conserved sequences and structures across various pest species. Structural models were produced using AlphaFold2 and SwissModel, followed by validation through SAVES. The virtual screening of 30,052 natural products conducted with AutoDock Vina revealed NPA001937 as a leading binder to all three targets. Subsequent 500 ns molecular dynamics simulations (GROMACS) validated the stability and advantageous interaction profiles of the ligand- protein complexes. This compound presents several advantages over chemical insecticides, including its natural origin, ability to target multiple pathways, and a lower chance of resistance development. The results emphasize the effectiveness of computational methods in speeding up the discovery of agrochemicals which upon further experimental validation may serve as ecofriendly options for sustainable pest management.