Discovery of novel Trichoderma-based bioactive compounds for controlling potato virus Y based on molecular docking and molecular dynamics simulation techniques

Abstract

Abstract Background Although potato virus Y (PVY) is the most serious virus-infecting potato plants worldwide, the losses concurred by it remain unmanageable due to the lack of efficient anti-PVY agents. Hence, the objective of this study was to assess the antiviral properties of secondary metabolite compounds obtained from culture filtrates of four Trichoderma spp. isolates. The assessment was conducted using computational methods, including molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, as well as molecular dynamics simulations. The aim was to develop novel and effective agents for combating PVY. Results The GC–MS analysis of the studied Trichoderma spp. secondary metabolites revealed 24 compounds with relative amounts exceeding 10%. Molecular docking was then performed using MOE software to evaluate the activity of these compounds against the PVY protein coat (PDB-ID: 6HXX). Ningnanmycin and ribavirin, known plant virus inhibitors, were employed as reference ligands for comparison. Among the compounds tested, C9, C10, C13, and C19 exhibited superior docking scores, root mean square deviation (RMSD) values, and binding modes compared to the reference ligands. In addition, these compounds successfully passed the ADMET analysis. Further investigation focused on compounds C13 and C19, which underwent in-depth analysis through MDs for 100 ns. The MDs trajectories demonstrated that both complexes exhibited favorable stability, compactness, and binding modes throughout the simulation period. However, the C19/PVY-CP complex outperformed the C13 complex in all calculated parameters such as RMSD, root mean square fluctuation (RMSF), radius of gyration (RoG), solvent-accessible surface area (SASA), and intermolecular hydrogen bonds. Interestingly, these findings aligned with the results obtained from the docking analysis, indicating that C9 and C10 possess high potential against PVY, as they exhibited binding modes like that of C19. Conclusion These promising outcomes provide a solid foundation for considering the potential use of compounds C9, C10, C13, and C19 as antiviral agents. Further experimental validation and in-depth studies are warranted to assess the efficacy and safety of these compounds and their potential as antiviral therapeutics. To our knowledge, this is the first report to study the biological activities of the Trichoderma-based bioactive compounds against PVY using computational techniques. Graphical abstract