In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2
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College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
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Department of Surgery, Northshore University HealthSystem, Evanston, IL 60201, USA
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Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou 225009, China
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Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
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Institutes of Agricultural Science and Technology Development, Yangzhou University Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(10), 1141; https://doi.org/10.3390/v12101141
Received: 21 September 2020
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Revised: 2 October 2020
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Accepted: 5 October 2020
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Published: 8 October 2020
(This article belongs to the Special Issue Strategies for the Discovery of Antivirals against Respiratory RNA Viruses)
Janus kinase (JAK) inhibitors have been developed as novel immunomodulatory drugs and primarily used for treating rheumatoid arthritis and other inflammatory diseases. Recent studies have suggested that this category of anti-inflammatory drugs could be potentially useful for the control of inflammation “storms” in respiratory virus infections. In addition to their role in regulating immune cell functions, JAK1 and JAK2 have been recently identified as crucial cellular factors involved in influenza A virus (IAV) replication and could be potentially targeted for antiviral therapy. Gingerenone A (Gin A) is a compound derived from ginger roots and a dual inhibitor of JAK2 and p70 S6 kinase (S6K1). Our present study aimed to determine the antiviral activity of Gin A on influenza A virus (IAV) and to understand its mechanisms of action. Here, we reported that Gin A suppressed the replication of three IAV subtypes (H1N1, H5N1, H9N2) in four cell lines. IAV replication was also inhibited by Ruxolitinib (Rux), a JAK inhibitor, but not by PF-4708671, an S6K1 inhibitor. JAK2 overexpression enhanced H5N1 virus replication and attenuated Gin A-mediated antiviral activity. In vivo experiments revealed that Gin A treatment suppressed IAV replication in the lungs of H5N1 virus-infected mice, alleviated their body weight loss, and prolonged their survival. Our study suggests that Gin A restricts IAV replication by inhibiting JAK2 activity; Gin A could be potentially useful for the control of influenza virus infections.
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Keywords:
Gingerenone A; influenza A virus; JAK2; p70 S6 kinase; STAT3
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MDPI and ACS Style
Wang, J.; Prinz, R.A.; Liu, X.; Xu, X. In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2. Viruses 2020, 12, 1141. https://doi.org/10.3390/v12101141
AMA Style
Wang J, Prinz RA, Liu X, Xu X. In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2. Viruses. 2020; 12(10):1141. https://doi.org/10.3390/v12101141
Chicago/Turabian StyleWang, Jiongjiong, Richard A. Prinz, Xiufan Liu, and Xiulong Xu. 2020. "In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2" Viruses 12, no. 10: 1141. https://doi.org/10.3390/v12101141
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