The E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation.
Signal Transduct Target Ther
; 8(1): 53, 2023 02 03.
Article
in English
| MEDLINE | ID: covidwho-2232506
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Ubiquitin-Protein Ligases
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Limits:
Animals
/
Humans
Language:
English
Journal:
Signal Transduct Target Ther
Year:
2023
Document Type:
Article
Affiliation country:
S41392-023-01335-5
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