Inhibition effects of novel polyketide compound PPQ-B against influenza A virus replication by interfering with the cellular EGFR pathway
Inhibition effects of novel polyketide compound PPQ-B against influenza A virus replication by interfering with the cellular EGFR pathway
复制标题
新型聚酮化合物PPQ-B通过干扰细胞EGFR通路抑制甲型流感病毒复制
DOI：
10.1016/j.antiviral.2017.04.007
复制
发表时间：
2017
影响因子：
7.6
通讯作者：
Zhu Weiming
中科院分区：
文献类型：
--
作者：
Wang Miaomiao;Wang Shuyao;Wang Wei;Wang Yi;Wang Hui;Zhu Weiming
开发具有新靶点和低毒性的抗甲型流感病毒（IAV）药物对于预防流感爆发至关重要。在本研究中，我们的结果表明，源自耐酸真菌Penicillium purpurogenumstrain JS03-21的新型聚酮化合物purpurquinone B（PPQ-B）可以低毒地抑制IAV的体外复制，并可能阻断病毒吸附后的某些阶段。 PPQ-B 可以在体外抑制 H1N1 (A/Puerto Rico/8/34; PR8)、H1N1 (A/California/04/2009; Cal09) 和 H3N2 (A/swine/Minnesota/02719/2009) 病毒复制，表明 PPQ-B 具有广谱抗 IAV 活性。 PPQ-B 的抗病毒活性可能很大程度上与其对吸附后 0-4 小时发生的某些步骤的抑制有关。口服 PPQ-B 可以降低 IAV 感染小鼠的肺部病毒滴度并提高存活率。 PPQ-B 还显着降低 IAV 感染的肺部和 A549 细胞中炎症因子 TNF-α、IL-6、RANTES 和 KC 的产生，表明 PPQ-B 还可能减弱 IAV 感染引起的炎症反应。 PPQ-B 可能下调 NF-κB 和 MAPK 通路，从而抑制病毒复制和炎症反应。综上所述，PPQ-B未来有潜力开发成针对宿主EGFR通路的新型抗IAV药物。
Development of anti-influenza A virus (IAV) drugs with novel targets and low toxicity is critical for preparedness against influenza outbreaks. In the current study, our results indicated that the novel polyketide compound purpurquinone B (PPQ-B) derived from acid-tolerant fungusPenicillium purpurogenumstrain JS03-21 suppressed the replication of IAVin vitrowith low toxicity, and may block some stages after virus adsorption. PPQ-B could inhibit H1N1 (A/Puerto Rico/8/34; PR8), H1N1 (A/California/04/2009; Cal09) and H3N2 (A/swine/Minnesota/02719/2009) virus replicationin vitro, suggesting that PPQ-B possesses broad-spectrum anti-IAV activities. PPQ-B's antiviral activity may be largely related to its inhibition of some steps that occur 0–4 h after adsorption. Oral administration of PPQ-B could decrease pulmonary viral titers and improve survival rate in IAV infected mice. PPQ-B also significantly decreased the production of inflammatory factors TNF-α, IL-6, RANTES and KC in IAV infected lungs and A549 cells, suggesting that PPQ-B may also attenuate the inflammatory responses caused by IAV infection. PPQ-B may down-regulate the NF-κB and MAPK pathways to inhibit both virus replication and inflammatory responses. In summary, PPQ-B has the potential to be developed into a novel anti-IAV drug targeting host EGFR pathway in the future.