Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Li Z 

PROVIDER: S-EPMC9897159 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Li Zhaolong Z   Hao Pengfei P   Zhao Zhilei Z   Gao Wenying W   Huan Chen C   Li Letian L   Chen Xiang X   Wang Hong H   Jin Ningyi N   Luo Zhao-Qing ZQ   Li Chang C   Zhang Wenyan W  

Signal transduction and targeted therapy 20230203 1


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-prote  ...[more]

Similar Datasets

| S-EPMC10865846 | biostudies-literature
| S-EPMC8997491 | biostudies-literature
| S-EPMC10865787 | biostudies-literature
| S-EPMC10082641 | biostudies-literature
| S-EPMC9587004 | biostudies-literature
| S-EPMC8069661 | biostudies-literature
| S-EPMC7762499 | biostudies-literature
| S-EPMC7843238 | biostudies-literature
2024-09-12 | GSE277027 | GEO
| S-EPMC8666140 | biostudies-literature