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Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virusinduced oxidative stress

Acta Pharmaceutica Sinica B 2023年第1期13卷 174-191页

作者： Eun-Bin Kwon Wei Li Young Soo Kim Buyun Kim Hwan-Suck Chung younghoon go Hyun-Jeong Ko Jae-Hyoung Song Young Ho Kim Chun Whan Choi Jang-Gi Choi Korean Medicine(KM)Application Center Korea Institute of Oriental MedicineDaegu 41062Republic of Korea College of Pharmacy Chungnam National UniversityDaejeon 34134Republic of Korea Natural Product Research Team BiocenterGyeonggido Business and Science AcceleratorGyeonggi-Do 16229Republic of Korea Laboratory of Microbiology and Immunology College of PharmacyKangwon National UniversityChuncheon 24341Republic of Korea

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral ***,neuraminidase(NA)inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration(FDA)for the prevention and treatment of ***,we show that vitisin B(VB)inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 *** 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 *** decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity,and inhibiting NF-κB translocation to the nucleus through IKK *** addition,VB reduced body weight loss,increased survival,decreased viral replication and the inflammatory response in the lungs of influenza A virus(IAV)-infected *** together,our results indicate that VB is a promising therapeutic candidate against IAV infection,complements existing drug limitations targeting viral *** modulated the intracellular ROS by G6PD,Nrf2 antioxidant response pathway,and NF-κB signaling *** results demonstrate the feasibility of a multi-targeting drug strategy,providing new approaches for drug discovery against IAV infection.

关键词： Influenza Vitisin B Vitis vinifera L. Neuraminidase Reactive oxygen species NF-κB Multi-targeting Nrf2 G6PD

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