Vitiello Mariaterasa, Galdiero Marilena, Galdiero Massimiliano
Department of Experimental Medicine, Second University of Naples, Via L. De Crecchio 7, Naples 80138, Italy.
Protein Pept Lett. 2009;16(7):786-93. doi: 10.2174/092986609788681742.
Enveloped animal viruses fuse their membrane with a host cell membrane in order to deliver their genome into the cytoplasm of the cell and thus initiating infection. This crucial step is mediated by virally encoded transmembrane proteins that, following an appropriate triggering, insert their fusion peptides into the target membrane and, through a cascade of conformational changes, drive the merging of the two apposing membranes. The battle against viruses is ongoing with the constant threat of viruses developing resistance to present drugs and emerging viruses, therefore there is a continuous challenge to improve our defence strategies. Entry inhibitors are currently in development for diverse human and animal viral pathogens, and advances in our understanding on how viral entry proteins undergo conformational changes that lead to entry offer a huge potential for the development of novel therapeutics. This review describes recent advances on viral-mediated fusion mechanisms concentrating on the development of peptidic inhibitors of membrane fusion.
有包膜的动物病毒将其膜与宿主细胞膜融合，以便将其基因组传递到细胞细胞质中，从而引发感染。这一关键步骤由病毒编码的跨膜蛋白介导，在适当的触发后，这些蛋白将其融合肽插入靶膜，并通过一系列构象变化驱动两个相对膜的融合。对抗病毒的斗争一直在进行，因为病毒不断有产生对现有药物的抗性和出现新病毒的威胁，因此改进我们的防御策略一直是一项持续的挑战。目前正在为多种人类和动物病毒病原体开发进入抑制剂，我们对病毒进入蛋白如何经历导致进入的构象变化的理解取得的进展为新型治疗方法的开发提供了巨大潜力。本综述描述了病毒介导的融合机制的最新进展，重点是膜融合肽抑制剂的开发。
