In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2

Abstract

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.

Therapeutic potential of ginger against COVID-19: Is there enough evidence?

“…17 The in vitro experiments indicated that gingerenone inhibits the replication of the several subtypes of influenza A virus (H1N1, H5N1 and H9N2). 19 The influenza A virus replication is also reduced in the lungs of gingerenone-treated mice. 19 Furthermore, some ginger-derived components exhibit anti-influenza activity and can prevent swine flu infection.…”

“… 19 The influenza A virus replication is also reduced in the lungs of gingerenone-treated mice. 19 Furthermore, some ginger-derived components exhibit anti-influenza activity and can prevent swine flu infection. 26 The extract of Zingiber montanum also reduces the infectivity of avian influenza virus H5N1 in vitro .…”

Zingiber officinale: Ayurvedic Uses of the Plant and In Silico Binding Studies of Selected Phytochemicals With Mpro of SARS-CoV-2

“…Gingerenone-A, because of its ability to inhibit JAK2 (Janus kinase 2), which kinase is a crucial factor in IAV replication, has been mentioned as a potential IAV therapeutic. 24 In molecular docking simulation using Hex software, gingerenone-A showed best binding affinities to Mpro and S protein compared to other phytochemicals of Z .officinale. 56 Our results suggest that CA and hesperidin can prove to be good therapeutics for COVID-19.…”

Development and Effects of Influenza Antiviral Drugs

“…It is worth noting that Punicalagin also had a significant inhibitory effect on oseltamivir-resistant strains [ 102 ]. In addition, the ginger extract Gingerenone A acts as a dual inhibitor of JAK2 and p70S6 kinase (S6K1) to inhibit influenza virus replication by inhibiting JAK2 activity and interfering with viral assembly [ 103 ].…”