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AIM Influenza A virus (IAV) resistance to available antiviral agents urges us to discover new drugs.Natural flavonoids have been reported for their antiviral activities.In this paper, the anti-influenza viral and anti-inflammatory effects of a series of synthesized flavonoid derivatives were studied.METHODS The cellular protective effects of the flavonoid derivatives were evaluated by cytopathic effect (CPE) assay.The direct antiviral replication effects of "Hits" were studied by neuraminidase (NA) activity reduction assay, a real-time quantitative PCR assay for the intracellular gene expression of viral haemagglutination (HA), and an immunofluorescence assay for the intracellular protein expression of viral NP and M2.Besides, their inhibitory effects on the production of proinflammatory cytokines induced by influenza infection were studied.RESULTS More than 100 synthesized flavonoid derivatives were evaluated, J27113 and J27116 from these compounds exhibited the most protective effects in the CPE reduction assay.They Inhibited the NA activity, and decreased HA gene and NP, M2 protein expression.Furthermore, they showed inhibitory effects on the production of IL-6, IL-8, MCP-1 and RANTES.CONCLUSION The inhibition on the replication of influenza virus and their antiinflammatory effects of J27113 and J27116 may be considered as the major components for their cellular protective effects against influenza, which will provide information for novel antiviral drug development.