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

DMO-CAP 通过激活血红素加氧酶-1 介导的 IFN 反应来抑制流感病毒复制

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作者:Ming Zhong, Huiqiang Wang, Linlin Ma, Haiyan Yan, Shuo Wu, Zhengyi Gu, Yuhuan Li

Background

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

Conclusions

DMO-CAP inhibited IAV replication by activating HO-1-mediated IFN response. DMO-CAP may be a potential agent or supplement against IAV infection.

Methods

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.

Results

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. Conclusions: DMO-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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