The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation

文献类型： 外文期刊

第一作者： Li, Zhaolong

作者： Li, Zhaolong;Zhao, Zhilei;Gao, Wenying;Huan, Chen;Chen, Xiang;Wang, Hong;Luo, Zhao-Qing;Zhang, Wenyan;Hao, Pengfei;Li, Letian;Jin, Ningyi;Li, Chang

作者机构：

期刊名称：SIGNAL TRANSDUCTION AND TARGETED THERAPY （ 影响因子：39.3； 五年影响因子：37.2 ）

ISSN： 2095-9907

年卷期： 2023 年 8 卷 1 期

页码：

收录情况： SCI

摘要： The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it a potential target for therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine, leading to its degradation by the ubiquitin-proteasome system (UPS). Importantly, RNF5-induced degradation of E inhibits SARS-CoV-2 replication and the RNF5 pharmacological activator Analog-1 alleviates disease development in a mouse infection model. We also found that RNF5 is distinctively expressed in different age groups and in patients displaying different disease severity, which may be exploited as a prognostic marker for COVID-19. Furthermore, RNF5 recognized the E protein from various SARS-CoV-2 strains and SARS-CoV, suggesting that targeting RNF5 is a broad-spectrum antiviral strategy. Our findings provide novel insights into the role of UPS in antagonizing SARS-CoV-2 replication, which opens new avenues for therapeutic intervention to combat the COVID-19 pandemic.

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