Indian Medicinal Plant-Derived Phytochemicals as Potential Antidotes for Snakebite: A Pharmacoinformatic Study of Atrolysin Inhibitors

Snakebite envenoming is a significant health threat, particularly in tropical regions, causing substantial morbidity and mortality. Traditional treatments, including antivenom therapy, have limitations and associated risks. This research aims to discover novel phytochemical antidotes for snakebites, specifically targeting the western diamondback rattlesnake (<i>Crotalus atrox</i>) venom metalloproteinase Atrolysin. Utilizing pharmacoinformatic techniques such as molecular docking, high-throughput ligand screening, pharmacophore mapping, pharmacokinetic profiling, and molecular dynamics (MD) simulations, we analyzed phytochemicals from the Indian Medicinal Plants, Phytochemistry And Therapeutics (IMPPAT) database alongside well-known nine metalloproteinase inhibitors from the PubChem database. From an initial set of 17,967 compounds, 4708 unique compounds were identified for further study. These compounds were evaluated based on drug likeness, molecular descriptors, ADME properties, and toxicity profiles. Binding site predictions and molecular docking identified key interacting residues and binding energies, highlighting several promising compounds. Density functional theory (DFT) analysis provided insights into these compounds' electronic properties and stability. MD simulations assessed the dynamic stability of protein-ligand complexes using parameters such as RMSD, RMSF, the radius of gyration, and hydrogen bond interactions. This study identified top candidates, including CID5291, IMPHY001495, IMPHY014737, IMPHY008983, IMPHY008176, and IMPHY003833, based on their favorable binding energies, interaction forces, and structural stability. These findings suggest that the selected phytochemicals have the potential to serve as effective alternatives to traditional antivenom treatments, offering a promising avenue for further research and development in snakebite management.