The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics.Currently,neuraminidase(NA)inhibitors are commonly used antiviral drugs approved by the US F...The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics.Currently,neuraminidase(NA)inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration(FDA)for the prevention and treatment of influenza.Here,we show that vitisin B(VB)inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells.Reactive oxygen species(ROS),which frequently occur during viral infection,increase virus replication by activating the NF-κB signaling pathway,downmodulating glucose-6-phosphate dehydrogenase(G6PD)expression,and decreasing the expression of nuclear factor erythroid2-related factor 2(Nrf2)antioxidant response activity.VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity,and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation.In addition,VB reduced body weight loss,increased survival,decreased viral replication and the inflammatory response in the lungs of influenza A virus(IAV)-infected mice.Taken together,our results indicate that VB is a promising therapeutic candidate against IAV infection,complements existing drug limitations targeting viral NA.It modulated the intracellular ROS by G6PD,Nrf2 antioxidant response pathway,and NF-κB signaling pathway.These results demonstrate the feasibility of a multi-targeting drug strategy,providing new approaches for drug discovery against IAV infection.展开更多
基金supported by the National Research Foundation of Korea(NRF)grant funded 2021R1A2C2094436 and 2020R1C1C1006749the Korea Institute of Oriental Medicine grant number KSN2022230 provided by the Ministry of Science and ICT,Korea。
文摘The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics.Currently,neuraminidase(NA)inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration(FDA)for the prevention and treatment of influenza.Here,we show that vitisin B(VB)inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells.Reactive oxygen species(ROS),which frequently occur during viral infection,increase virus replication by activating the NF-κB signaling pathway,downmodulating glucose-6-phosphate dehydrogenase(G6PD)expression,and decreasing the expression of nuclear factor erythroid2-related factor 2(Nrf2)antioxidant response activity.VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity,and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation.In addition,VB reduced body weight loss,increased survival,decreased viral replication and the inflammatory response in the lungs of influenza A virus(IAV)-infected mice.Taken together,our results indicate that VB is a promising therapeutic candidate against IAV infection,complements existing drug limitations targeting viral NA.It modulated the intracellular ROS by G6PD,Nrf2 antioxidant response pathway,and NF-κB signaling pathway.These results demonstrate the feasibility of a multi-targeting drug strategy,providing new approaches for drug discovery against IAV infection.
