7,8-dihydroxyflavone and daphnetin have virucidal and neuraminidase inhibition activities against influenza A virus in vitro

Abstract

Influenza A virus remains a major global health concern, underscoring the need for novel antiviral agents. This study investigated the antiviral potential of two natural compounds, 7,8-dihydroxyflavone (DHF) and daphnetin (DAP), against influenza A viruses in vitro. Following in vitro cytotoxicity and antioxidative activity assessments, the antiviral effects of DHF and DAP were evaluated, with a particular focus on their direct viral inhibition. DHF and DAP demonstrated complete virucidal activity influenza A virus at concentrations of 50 µM and 100 µM, respectively. However, neither compound inhibited influenza surface protein hemagglutination (HA), suggesting that their virucidal effects are independent of HA receptor binding. Both compounds exhibited neuraminidase (NA) inhibition, with DAP showing stronger activity compared to DHF. Furthermore, DHF and DAP suppressed influenza virus replication in cells, as evidenced by a reduction in green fluorescence protein (GFP) reporter expression in virus-infected cells. Growth kinetics analysis revealed that both compounds significantly reduced viral replication when applied to cells before or after viral infection. These findings demonstrate that DHF and DAP exhibit multifaceted antiviral activity, including direct virucidal action, NA inhibition, and suppression of viral replication. Our results suggest that DHF and DAP are promising candidates for the development of novel influenza therapeutics.