Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virus-induced oxidative stress.
10.1016/j.apsb.2022.07.001
- Author:
Eun-Bin KWON
1
;
Wei LI
1
;
Young Soo KIM
1
;
Buyun KIM
1
;
Hwan-Suck CHUNG
1
;
Younghoon GO
1
;
Hyun-Jeong KO
2
;
Jae-Hyoung SONG
2
;
Young Ho KIM
3
;
Chun Whan CHOI
4
;
Jang-Gi CHOI
1
Author Information
1. Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Republic of Korea.
2. Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea.
3. College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea.
4. Natural Product Research Team, Biocenter, Gyeonggido Business and Science Accelerator, Gyeonggi-Do 16229, Republic of Korea.
- Publication Type:Journal Article
- Keywords:
G6PD;
Influenza;
Multi-targeting;
NF-κB;
Neuraminidase;
Nrf2;
Reactive oxygen species;
Vitis vinifera L.;
Vitisin B
- From:
Acta Pharmaceutica Sinica B
2023;13(1):174-191
- CountryChina
- Language:English
-
Abstract:
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 erythroid 2-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.
