Section of Biochemistry, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
Section of Haematology, Department of Scienze Mediche Chirurgiche e Tecnologie Avanzate "G.F. Ingrassia", University of Catania, 95123 Catania, Italy.
Int J Mol Sci. 2020 May 20;21(10):3622. doi: 10.3390/ijms21103622.
The COVID-19 global pandemic is caused by SARS-CoV-2, and represents an urgent medical and social issue. Unfortunately, there is still not a single proven effective drug available, and therefore, current therapeutic guidelines recommend supportive care including oxygen administration and treatment with antibiotics. Recently, patients have been also treated with off-label therapies which comprise antiretrovirals, anti-inflammatory compounds, antiparasitic agents and plasma from convalescent patients, all with controversial results. The ubiquitin-proteasome system (UPS) is important for the maintenance of cellular homeostasis, and plays a pivotal role in viral replication processes. In this review, we discuss several aspects of the UPS and the effects of its inhibition with particular regard to the life cycle of the coronaviruses (CoVs). In fact, proteasome inhibition by various chemical compounds, such as MG132, epoxomycin and bortezomib, may reduce the virus entry into the eucariotic cell, the synthesis of RNA, and the subsequent protein expression necessary for CoVs. Importantly, since UPS inhibitors reduce the cytokine storm associated with various inflammatory conditions, it is reasonable to assume that they might be repurposed for SARS-CoV-2, thus providing an additional tool to counteract both virus replication as well as its most deleterious consequences triggered by abnormal immunological response.
新型冠状病毒肺炎（COVID-19）大流行由 SARS-CoV-2 引起，是一个紧迫的医学和社会问题。遗憾的是，目前仍没有一种经证实有效的药物，因此，目前的治疗指南建议提供支持性护理，包括吸氧和使用抗生素治疗。最近，还对患者采用了标签外治疗，包括抗逆转录病毒药物、抗炎化合物、抗寄生虫药物和来自康复患者的血浆，所有这些治疗都有争议的结果。泛素-蛋白酶体系统（UPS）对于维持细胞内稳态很重要，并且在病毒复制过程中发挥关键作用。在这篇综述中，我们讨论了 UPS 的几个方面及其抑制作用，特别是针对冠状病毒（CoV）的生命周期。事实上，各种化学化合物（如 MG132、表霉素和硼替佐米）对蛋白酶体的抑制作用可能会降低病毒进入真核细胞的能力、RNA 的合成以及随后 CoV 所需的蛋白表达。重要的是，由于 UPS 抑制剂可减少与各种炎症状态相关的细胞因子风暴，因此可以合理地假设它们可能被重新用于治疗 SARS-CoV-2，从而为对抗病毒复制及其由异常免疫反应引发的最具破坏性后果提供了另一种手段。
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