GC‐MS Profiling and Anti‐Influenza Potential of <i>Phyllanthus emblica</i> (Indian Gooseberry) Extract: In Vitro and In Silico Approaches

ABSTRACT Influenza A virus remains a persistent global health challenge requiring novel therapeutic interventions. This study evaluated the antiviral efficacy of aqueous, ethanolic, and methanolic extracts of Phyllanthus emblica against the H1N1pdm09 virus and identified active compounds (GCMS) through molecular docking analysis. Cytotoxicity was determined using MTT assays, and more than 95% viability was found at concentrations of 62.50 µg/mL for the aqueous extract, 125 µg/mL for the ethanolic &amp; methanolic extract. In contrast, antiviral activity was assessed through RT‐qPCR quantification of viral genomic load via cycle threshold (Ct) values across pre‐treatment, co‐treatment, and post‐treatment protocols. Antioxidant activity was evaluated using DPPH assays, and molecular docking examined binding affinities against key viral proteins. The aqueous extract demonstrated negligible antiviral activity, while ethanolic and methanolic extracts showed substantial efficacy, particularly under co‐treatment conditions. Ethanolic extract achieved the highest viral inhibition with Ct values of 27.09 ( p &lt;0.0001), while methanolic extract showed Ct values of 25.25 ( p &lt;0.0001) in co‐treatment compared to virus control (Ct). Antioxidant analysis revealed superior activity in the methanolic extract (IC 50 = 1.044 ± 02 µg/mL) compared to the ethanolic extract (IC 50 = 5.769 ± 02 µg/mL). These biological activities are attributed to the rich presence of phenolic and triterpenoids identified in the extracts. Molecular docking identified γ‐sitosterol as the most potent compound with potential binding affinities, including M2 protein (−10.98), neuraminidase (−7.68), RdRp (−9.52), and hemagglutinin (−9.94 kcal/mol). P. emblica extracts demonstrate significant anti‐influenza activity through multi‐target mechanisms, positioning this natural source as a valuable candidate for sustainable antiviral drug development, and γ‐sitosterol is identified as a strong M2 inhibitor.