Institute of Immunology, Centre de Recherche Public-Santé/Laboratoire National de Santé, Luxembourg.
Trends Pharmacol Sci. 2012 Feb;33(2):89-99. doi: 10.1016/j.tips.2011.10.004. Epub 2011 Dec 22.
At the global level, influenza A virus (IAV) is considered a major health threat because it causes significant morbidity. Different treatment and prevention options have been developed; however, these are insufficient in the face of recent IAV outbreaks. In particular, available antiviral agents have limited effectiveness owing to IAV resistance to these virus-directed drugs. Recent advances in understanding of IAV replication have revealed a number of cellular drug targets that counteract viral drug resistance. This review summarizes current knowledge on IAV replication with a focus on emerging cellular drug targets. Interestingly, for many of these targets, compounds for which safety testing has been carried out in humans are available. It is possible that some of these compounds, such as inhibitors of heat shock protein 90, proteasome, importin α5 or protein kinase C, will be used for treatment of IAV infections after careful evaluation in human primary cells and severely ill flu patients.
在全球范围内，甲型流感病毒（IAV）被认为是一个主要的健康威胁，因为它会导致严重的发病率。已经开发出不同的治疗和预防选择；然而，面对最近的 IAV 爆发，这些选择还不够。特别是，由于 IAV 对这些病毒靶向药物的耐药性，现有的抗病毒药物效果有限。对 IAV 复制的深入了解揭示了许多对抗病毒耐药性的细胞药物靶点。本综述总结了 IAV 复制的最新知识，重点介绍了新兴的细胞药物靶点。有趣的是，对于其中许多靶点，已经有在人类中进行安全性测试的化合物可用。这些化合物中的一些，如热休克蛋白 90、蛋白酶体、importin α5 或蛋白激酶 C 的抑制剂，在经过对人类原代细胞和重症流感患者的仔细评估后，可能会被用于治疗 IAV 感染。
