期刊
VIROLOGY JOURNAL
卷 16, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12985-019-1125-9
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资金
- National Nature Science Foundation of China (NSFC) [U1303224, 81630089]
- CAMS Initiative for Innovative Medicine [2017-I2M-3-010]
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX09711003-005-004]
- Open Foundation of NHC Key Laboratory of Biotechnology of Antibiotics [NHC KLBA201802]
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.
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