Plant polyphenols as broad-spectrum antivirals: Comprehensive potency profiling against major virus families

Plant polyphenols are promising candidates for broad-spectrum antiviral development, but their comparative potency and selectivity across virus families remain poorly characterized. This study aims to systematically compare and profile the antiviral activity, potency, and selectivity of diverse plant polyphenol classes across major virus families relevant to human and animal health. A comprehensive literature search was conducted across five databases to identify studies reporting in vitro and in vivo antiviral activity of plant polyphenols, extracting quantitative IC₅₀/EC₅₀ and selectivity index data. Potency matrices were constructed, and comparative visualizations, including heatmaps, violin plots, and radar charts, were generated to assess the spectrum and strength of antiviral effects. Analysis of 54 studies revealed that flavonoids, catechins, phlorotannins, and biflavonoids frequently exhibit sub- to low-micromolar IC₅₀/EC₅₀ values against multiple virus families, particularly Orthomyxoviridae, Flaviviridae, and Coronaviridae. Certain scaffolds, such as dieckol and quercetin, demonstrated potent and broad activity (median IC₅₀ <10 µM) with favorable selectivity indices. In vivo efficacy data, though limited, confirmed survival or viral load reductions in animal models. The findings highlight several polyphenol scaffolds with robust, multi-family antiviral activity and high selectivity, underscoring their potential for broad-spectrum antiviral drug discovery. Considering all, standardized evaluation and further translational research are warranted to optimize lead candidates.