Structure-based discovery of Saponarin as a broad-spectrum allosteric inhibitor of banana viral coat proteins

Abstract

Banana (Musa spp.), a globally significant staple crop, suffers substantial yield losses from persistent viral infections caused by Banana Bunchy Top Virus (BBTV), Banana Streak Virus (BSV), Banana Bract Mosaic Virus (BBrMV), and Banana Mosaic Virus (BMoV). Given the critical role of viral coat proteins (CPs) in genome encapsidation, movement, and host infectivity, these capsid components represent attractive targets for antiviral intervention. Here, we report a comprehensive in silico pipeline integrating homology modeling, structure-based molecular docking, pharmacokinetic profiling, and 100-ns all-atom molecular dynamics (MD) simulations to identify potential CP inhibitors from a curated phytochemical library. High-confidence structural models of the CPs were generated using SWISS-MODEL and AlphaFold3 and validated via Ramachandran analysis, ERRAT, and Verify3D. Virtual screening of 100 plant-derived compounds revealed Saponarin, a flavonoid glucoside, as the top-scoring molecule across all viral targets, with docking scores ranging from -13.33 to -8.75 kcal/mol. Binding interactions were dominated by extensive hydrogen bonds and {pi}-based stacking with conserved aromatic and polar residues within the capsid interface pockets. ADMET predictions indicated Saponarin possesses favorable physicochemical properties, high aqueous compatibility, low clearance, and minimal ecotoxicological risk. MD simulations confirmed stable binding, persistent hydrogen bonding, and conserved protein compactness, supporting an allosteric inhibition mechanism. These findings establish Saponarin as a structurally and pharmacologically viable broad-spectrum antiviral candidate for banana virus control, warranting experimental validation for translational deployment in sustainable crop protection strategies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=44 SRC="FIGDIR/small/662402v2_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@44d761org.highwire.dtl.DTLVardef@1982aa5org.highwire.dtl.DTLVardef@117eabeorg.highwire.dtl.DTLVardef@13495d9_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Schematic representation of the structure-based virtual screening workflow for identifyin broad-spectrum inhibitors targeting coat proteins (CPs) of BBTV, BSV, BBrMV, and BMoV. Homology models of CPs were constructed, followed by binding site prediction, ligand retrieval, and molecular docking of 100 phytochemicals. Saponarin emerged as the top candidate, showing strong binding at conserved allosteric sites. ADMET profiling confirmed favorable pharmacokinetics and low toxicity. Molecular dynamics simulations validated the stability of Saponarin-CP complexes, supporting its potential as a broad-spectrum antiviral agent against multiple banana viruses. C_FIG