Identification of potential plant secondary metabolites targeting begomovirus-associated betasatellite virulence factor βC1 protein through molecular docking, simulation and MM-PBSA studies

The βC1 protein encoded by begomoviruses plays a key role in counteracting plant defense mechanisms, making it a prime target for antiviral compounds. Here, we investigated the role of plant secondary metabolites for their antiviral potential. Initially, the tertiary structure of βC1 protein was predicted and docked to 2851 plant secondary metabolites along with positive controls ribavirin and ningnanmycin. Additionally, 43 analogues of the ligand with highest dock score were created and assessed against the βC1 protein to see if they offered better binding energy than the initial compound. To check the protein–ligand complex's stability, we performed a 100 ns molecular dynamics (MD) simulation, then measured the change in Gibbs free energy (ΔG) using the molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) approach. Our study found that Anonaine, a bioactive compound, had a high binding score of − 6.0 kcal/mol, with its analogues a33 and a41 scoring − 6.8 kcal/mol and − 6.6 kcal/mol, respectively. Molecular dynamics simulations for these complexes showed stable interactions, with minimal changes in root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values. Additionally, the protein–ligand complexes showed consistent hydrogen bond formation, with negligible changes in the radius of gyration (Rg) and solvent-accessible surface area (SASA). The binding free energy (ΔG) calculations revealed estimated values of − 16.99 ± 2.16, − 18.29 ± 1.91, and − 27.26 ± 2.11 for the βC1-Anonaine, βC1-a33, and βC1-a44 protein–ligand complexes, respectively. In silico toxicity predictions suggest top ligands are less toxic, making them ideal for biopesticide development. Overall, these findings reveal the potential of plant secondary metabolites as promising agents in controlling begomovirus infections.