Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
Int J Biol Sci. 2022 Jul 11;18(12):4731-4743. doi: 10.7150/ijbs.72482. eCollection 2022.
The ongoing COVID-19 pandemic is caused by an RNA virus, SARS-CoV-2. The genome of SARS-CoV-2 lacks a nuclear phase in its life cycle and is replicated in the cytoplasm. However, interfering with nuclear trafficking using pharmacological inhibitors greatly reduces virus infection and virus replication of other coronaviruses is blocked in enucleated cells, suggesting a critical role of the nucleus in virus infection. Here, we summarize the alternations of nuclear pathways caused by SARS-CoV-2, including nuclear translocation pathways, innate immune responses, mRNA metabolism, epigenetic mechanisms, DNA damage response, cytoskeleton regulation, and nuclear rupture. We consider how these alternations contribute to virus replication and discuss therapeutic treatments that target these pathways, focusing on small molecule drugs that are being used in clinical studies.
持续的 COVID-19 大流行是由一种 RNA 病毒 SARS-CoV-2 引起的。SARS-CoV-2 的基因组在其生命周期中缺乏核相，并且在细胞质中复制。然而，使用药理学抑制剂干扰核转运会大大降低病毒感染，并且去核细胞中其他冠状病毒的复制被阻断，这表明核在病毒感染中起关键作用。在这里，我们总结了由 SARS-CoV-2 引起的核途径的改变，包括核易位途径、先天免疫反应、mRNA 代谢、表观遗传机制、DNA 损伤反应、细胞骨架调节和核破裂。我们考虑了这些改变如何促进病毒复制，并讨论了针对这些途径的治疗方法，重点是正在临床研究中使用的小分子药物。
