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DMO-CAP inhibits influenza virus replication by activating heme oxygenase-1-mediated IFN response

tetano

Editor, Senior Moderator
Virol J. 2019 Feb 20;16(1):21. doi: 10.1186/s12985-019-1125-9.
[h=1]DMO-CAP inhibits influenza virus replication by activating heme oxygenase-1-mediated IFN response.[/h] Zhong M[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Wang H[SUP]1[/SUP], Ma L[SUP]4[/SUP], Yan H[SUP]1[/SUP], Wu S[SUP]1[/SUP], Gu Z[SUP]5[/SUP], Li Y[SUP]6[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] As 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.
[h=4]METHODS:[/h] The 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.
[h=4]RESULTS:[/h] DMO-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.
[h=4]CONCLUSIONS:[/h] DMO-CAP inhibited IAV replication by activating HO-1-mediated IFN response. DMO-CAP may be a potential agent or supplement against IAV infection.


PMID: 30786886 DOI: 10.1186/s12985-019-1125-9
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