Abstract
BackgroundAs a leading cause of respiratory disease, influenza A virus (IAV) infection remains a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapeutic drugs, development of new drugs is urgently required. Flavonoids extracted from Artemisia rupestris L. have an inhibitory effect on virus infections. Despite this fact, the antiviral properties of 6-demethoxy-4′-O-methylcapillarisin (DMO-CAP), one of such flavonoids, against the influenza virus have not been reported. Thus, the aim of this study is to investigate the anti-IAV virus efficacy and antiviral mechanism of DMO-CAP.MethodsThe inhibitory activity of DMO-CAP against IAV was detected in vitro using viral titers by Western blot analysis, qRT-PCR, and immunofluorescence assays. The mechanism of DMO-CAP against influenza virus was analyzed by Western blot analysis, qRT-PCR, and luciferase assay.ResultsDMO-CAP exhibits broad spectrum of antiviral activities against IAV in vitro. Mechanistically, DMO-CAP treatment induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK), JNK MAPK, and ERK MAPK, which led to the activation of Nrf2/heme oxygenase-1 (HO-1) pathway. Then, the up-regulation of HO-1 expression activated the IFN response and induced the expression of IFN-stimulated genes, thereby leading to efficient anti-IAV effects.ConclusionsDMO-CAP inhibited IAV replication by activating HO-1-mediated IFN response. DMO-CAP may be a potential agent or supplement against IAV infection.
Highlights
As a leading cause of respiratory disease, influenza A virus (IAV) infection remains a pandemic threat in annual seasonal outbreaks
To determine the antiviral activity of DMO-CAP, we initially studied the cytotoxicity of DMO-CAP in Madin-Darby canine kidney (MDCK) and RAW 264.7 cells cells by CCK assay
The highest concentration of DMO-CAP was set as 50 μM in the following antiviral assays, which confers minimal to no cellular cytotoxicity
Summary
As a leading cause of respiratory disease, influenza A virus (IAV) infection remains a pandemic threat in annual seasonal outbreaks. Flavonoids extracted from Artemisia rupestris L. have an inhibitory effect on virus infections Despite this fact, the antiviral properties of 6-demethoxy-4′-O-methylcapillarisin (DMO-CAP), one of such flavonoids, against the influenza virus have not been reported. Overpowering influenza by targeting host factors involved in viral replication is a potentially effective strategy. Such a strategy may weaken the virus’ ability to evolve resistance [10]. HO-1 regulates innate immunity and autoimmunity by modulating IFN-β production, which can control viral infections, such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus, Ebola virus, RSV, dengue, and influenza A virus (IAV) [13,14,15,16,17]. In 2012, Cummins et al demonstrated that HO-1 can regulate the immune response to influenza virus infection and vaccination in aged mice [17]
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