Evidence map›Paper›PMID 36737599›Full record

ArticleSignal transduction and targeted therapy2023

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

Zhaolong Li, Pengfei Hao, Zhilei Zhao, Wenying Gao, Chen Huan, Letian Li, Xiang Chen, Hong Wang, Ningyi Jin, Zhao-Qing Luo and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
11.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 58 citations in OpenAlex.

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  9. NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β-TrCP1/FBXO5 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Zhaolong LiDepartement of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Pengfei HaoResearch Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130000, Jilin, China.
Zhilei ZhaoDepartement of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Wenying GaoDepartement of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Chen HuanDepartement of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Letian LiResearch Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130000, Jilin, China.
Xiang ChenDepartement of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Hong WangDepartement of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Ningyi JinResearch Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130000, Jilin, China.
Zhao-Qing LuoDepartement of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China. luoz@jlu.edu.cn.
Chang LiResearch Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130000, Jilin, China. lichang78@163.com.ORCID 0000-0002-3267-1859
Wenyan ZhangDepartement of Infectious Diseases, Infectious Diseases and Pathogen Biology Center, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China. zhangwenyan@jlu.edu.cn.
Jilin University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

COVID-19Ubiquitin-Protein LigasesAnimalsAntiviral AgentsDNA-Binding ProteinsHumansMembrane ProteinsMicePandemicsSARS-CoV-2UbiquitinAntiviral AgentsDNA-Binding ProteinsMembrane ProteinsRNF5 protein, humanRNF5 protein, mouseUbiquitinUbiquitin-Protein Ligases

Identifiers

PMID36737599
PMCPMC9897159
OpenAlexW4319081135

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.