Institute of Molecular Virology, Centre of Molecular Biology of Inflammation, Westfälische Wilhelms-University of Muenster, Muenster, Germany.
PLoS One. 2013 May 23;8(5):e63657. doi: 10.1371/journal.pone.0063657. Print 2013.
Infections with influenza A viruses (IAV) are still amongst the major causes of highly contagious severe respiratory diseases not only bearing a devastating effect to human health, but also significantly impact the economy. Besides vaccination that represents the best option to protect from IAV infections, only two classes of anti-influenza drugs, inhibitors of the M2 ion channel and the neuraminidase, often causing resistant IAV variants have been approved. That is why the need for effective and amply available antivirals against IAV is of high priority. Here we introduce LADANIA067 from the leaves of the wild black currant (Ribes nigrum folium) as a potent compound against IAV infections in vitro and in vivo. LADANIA067 treatment resulted in a reduction of progeny virus titers in cell cultures infected with prototype avian and human influenza virus strains of different subtypes. At the effective dose of 100 µg/ml the extract did not exhibit apparent harming effects on cell viability, metabolism or proliferation. Further, viruses showed no tendency to develop resistance to LADANIA067 when compared to amantadine that resulted in the generation of resistant variants after only a few passages. On a molecular basis the protective effect of LADANIA067 appears to be mainly due to interference with virus internalisation. In the mouse infection model LADANIA067 treatment reduces progeny virus titers in the lung upon intranasal application. In conclusion, an extract from the leaves of the wild black currant might be a promising source for the development of new antiviral compounds to fight IAV infections.
甲型流感病毒 (IAV) 的感染仍然是高度传染性严重呼吸道疾病的主要原因之一,不仅对人类健康造成破坏性影响,还对经济产生重大影响。除了疫苗接种是预防 IAV 感染的最佳选择外,仅有两类抗流感药物,即 M2 离子通道抑制剂和神经氨酸酶抑制剂,经常导致产生耐药性的 IAV 变种。这就是为什么需要针对 IAV 的有效且广泛可用的抗病毒药物。在这里,我们介绍来自野生黑醋栗(黑醋栗叶)的 LADANIA067,作为一种针对 IAV 感染的有效化合物,具有体外和体内活性。LADANIA067 治疗可降低感染原型禽源和人源流感病毒不同亚型的细胞培养物中的病毒子代滴度。在 100µg/ml 的有效剂量下,该提取物对细胞活力、代谢或增殖没有明显的有害影响。此外,与金刚烷胺相比,病毒没有产生对 LADANIA067 的耐药性倾向,金刚烷胺在仅几次传代后就产生了耐药变体。从分子基础上看,LADANIA067 的保护作用主要似乎是由于干扰了病毒的内化。在小鼠感染模型中,经鼻应用 LADANIA067 可降低肺中的病毒子代滴度。总之,野生黑醋栗叶提取物可能是开发新型抗流感病毒化合物以对抗 IAV 感染的有前途的来源。