Leveraging computational intelligence to identify plant-derived compounds targeting TSWV-thrips protein interactions

Using in silico-based methods represents a cost-effective approach to rapidly identify safe and high-efficacy nature-derived compounds for managing the Tomato Spot Wilt Virus (TSWV) and its thrips vector species. This study employed modeling, validation, and optimization of the virus's and its insect vector's protein structures to determine binding sites and conduct protein-protein docking. Hotspot residues were identified to perform protein-ligand docking against a library of natural compounds with known insecticidal or antiviral activity. Og1, 3-indolacetic acid, lithospermic acid, and scutellarin exhibited high binding affinity to all three proteins. ADMET analysis revealed og1 as a safe and eco-friendly inhibitor. Molecular dynamic simulations demonstrated that the N- and C-termini exhibit significant flexibility, while the binding sites for each ligand remain relatively stable. This flexibility in the termini could potentially enhance adaptability in movements, aiding in ligand binding and demonstrating a dynamic interaction between the protein and ligand. The H-bond occupancy of the virus's envelopment glycoprotein, thrips' endocuticle structural glycoprotein-GN, and the thrips' ATP synthase subunit alpha in complex with og1 ranged from 13.7% to 44.0%, 11%, and 10.5% to 36.7%, respectively. The free binding energy of these proteins complexed with og1 was calculated as -60.973, -41.243, and -48.517 kcal/mol, respectively. Based on PCA-based FEL analysis, representative structures from each energy basin provided further evidence of the structural differences among conformations. In conclusion, these findings suggest the potential of og1 as a basis for designing and developing a future bio-insecticide/bio-antiviral agent.