Department of Viroscience, Erasmus Medical Center , Rotterdam, the Netherlands.
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin, Ireland.
J Virol. 2023 Oct 31;97(10):e0132523. doi: 10.1128/jvi.01325-23. Epub 2023 Oct 12.
Itaconate derivates, as well as the naturally produced metabolite, have been proposed as antivirals against influenza virus. Here, the mechanism behind the antiviral effects of exogenous 4-octyl itaconate (4-OI), a derivative of itaconate, against the influenza A virus replication is demonstrated. The data indicate that 4-OI targets the cysteine at position 528 of the CRM1 protein, resulting in inhibition of the nuclear export of viral ribonucleoprotein complexes in a similar manner as previously described for other selective inhibitors of nuclear export. These results postulate a mechanism not observed before for this immuno-metabolite derivative. This knowledge is helpful for the development of derivatives of 4-OI as potential antiviral and anti-inflammatory therapeutics.
衣康酸衍生物，以及天然产生的代谢物，已被提议作为抗流感病毒的药物。在这里，展示了外源性 4-辛基衣康酸（4-OI），一种衣康酸的衍生物，对甲型流感病毒复制的抗病毒作用的机制。数据表明，4-OI 靶向 CRM1 蛋白位置 528 的半胱氨酸，导致病毒核糖核蛋白复合物的核输出抑制以类似于先前描述的其他选择性核输出抑制剂的方式。这些结果提出了一种以前未观察到的这种免疫代谢物衍生物的机制。这些知识有助于开发 4-OI 的衍生物作为潜在的抗病毒和抗炎治疗药物。
