Computational Profiling of Plant-Derived Compounds Reveals Poly-pharmacological Potential for Multi-Target Antiviral Therapy

Abstract

The increasing prevalence of viral resistance and the multifactorial nature of viral pathogenesis necessitate the exploration of alternative therapeutic paradigms, particularly those embracing multi-target mechanisms. Poly-pharmacology wherein single compounds interact with multiple molecular targets has emerged as a strategic approach for the development of broad-spectrum antiviral agents. This study employs comprehensive computational analyses to elucidate the poly-pharmacological landscape of selected plant-derived bioactive compounds. Utilizing a multi-tiered in silico channel comprising molecular docking, target casting, pharmacophore mapping, molecular dynamics simulations, and network pharmacology, we systematically profiled the interactions of phytochemicals against a curated panel of viral proteins from SARS-CoV-2, Influenza A, and Hepatitis B virus (HBV). Compound-target predictions were conducted using Swiss-Target-Prediction and SEA, followed by docking simulations in Auto-Dock Vina and 100-ns molecular dynamics runs in GROMACS to validate binding stability. Target-pathway associations were analyzed via STRING and KEGG enrichment to interpret host-pathway modulation. Several compounds, including quercetin, kaempferol, and baicalin, exhibited high binding affinities across diverse viral targets, suggesting a potential for simultaneous disruption of viral entry, replication, and immune modulation. Functional enrichment and pathway analysis of predicted human targets further revealed modulatory effects on host pathways implicated in viral lifecycle regulation. These findings not only underscore the therapeutic promise of phytochemicals as multi-target antiviral agents but also provide a rational computational framework for their prioritization in drug discovery pipelines. The study paves the way for experimental validation and structure-guided optimization toward next-generation antiviral therapeutics sourced from natural products