Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
Biometals. 2024 Apr;37(2):289-304. doi: 10.1007/s10534-023-00558-x. Epub 2023 Nov 29.
The redox reactivity of iron is a double-edged sword for cell functions, being either essential or harmful depending on metal concentration and location. Deregulation of iron homeostasis is associated with several clinical conditions, including viral infections. Clinical studies as well as in silico, in vitro and in vivo models show direct effects of several viruses on iron levels. There is support for the strategy of iron chelation as an alternative therapy to inhibit infection and/or viral replication, on the rationale that iron is required for the synthesis of some viral proteins and genes. In addition, abnormal iron levels can affect signaling immune response. However, other studies report different effects of viral infections on iron homeostasis, depending on the class and genotype of the virus, therefore making it difficult to predict whether iron chelation would have any benefit. This review brings general aspects of the relationship between iron homeostasis and the nonspecific immune response to viral infections, along with its relevance to the progress or inhibition of the inflammatory process, in order to elucidate situations in which the use of iron chelators could be efficient as antivirals.
铁的氧化还原反应性对细胞功能来说是一把双刃剑,其作用既可能是必需的,也可能是有害的,具体取决于金属浓度和位置。铁稳态失调与多种临床情况有关,包括病毒感染。临床研究以及计算机模拟、体外和体内模型都表明,几种病毒会直接影响铁水平。基于铁是某些病毒蛋白和基因合成所必需的这一原理,铁螯合作用作为一种抑制感染和/或病毒复制的替代疗法具有一定的合理性。此外,异常的铁水平会影响信号免疫反应。然而,其他研究报告称,病毒感染对铁稳态的影响因病毒的类别和基因型而异,因此很难预测铁螯合作用是否会带来任何益处。本综述介绍了铁稳态与病毒感染引起的非特异性免疫反应之间的一般关系,以及其与炎症过程的进展或抑制之间的相关性,以便阐明使用铁螯合剂作为抗病毒药物可能有效的情况。