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Objective:To investigate the therapeutic efficacy of andrographolide,a plant derived compound,against chikungunya virus (CHIKV) infection.Methods:Using flow cytometry and immunoblotting assay,in vitro viral protein expression was studied in THP-1 cells line.In Balb/c mouse neonates,viral RNA copy number was determined by real time PCR.Results:The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells,Vero cells and THP-1 cell line.In vivo,andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number.Further,andrographolidc also increased cytotoxic T lymphocytcs both in vitro and in vivo.Andrographolide also activated host innate immune pathways,viz.,protein kinase R,phosphorylated eukaryotic initiation factor 2 α,retinoic acid inducible gene-Ⅰ and interferon regulatory factor 3/7,thereby increasing IFN-α secretion.CHIKV-induced nuclear factor κ light chain enhancer of activated B cells and tumor necrosis factor-α was also reduced on andrographolide treatment.Conclusion:Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.