Evidence map›Paper›PMID 42213583›Full record

ArticleeLife2026

Ubiquitin ligase ITCH regulates life cycle of SARS-CoV-2 virus.

Qiwang Xiang, Camille Wouters, Peixi Chang, Yu-Ning Lu, Mingming Liu, Haocheng Wang, Haley Heine, Sunning Qian, Junqin Yang, Andrew Pekosz and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Qiwang XiangDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0009-0001-4710-7572
Camille WoutersDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Peixi ChangDepartment of Veterinary Medicine, University of Maryland, College Park, United States.
Yu-Ning LuDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Mingming LiuDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Haocheng WangDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Haley HeineDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Sunning QianDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Junqin YangDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Andrew PekoszDepartment of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0000-0003-3248-1761
Yanjin ZhangDepartment of Veterinary Medicine, University of Maryland, College Park, United States.ORCID https://orcid.org/0000-0002-5847-3260
Jiou WangDepartment of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.ORCID https://orcid.org/0000-0001-9115-8708

Funding

NIH HHS NS074324
6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection poses a major threat to public health, and understanding the mechanism of viral replication and virion release would help identify therapeutic targets and effective drugs for combating the virus. Herein, we identified E3 ubiquitin protein ligase Itchy homolog (ITCH) as a central regulator of SARS-CoV-2 at multiple steps and processes. ITCH enhances the ubiquitination of viral envelope and membrane proteins and mutual interactions of structural proteins, thereby aiding in virion assembly. ITCH-mediated ubiquitination also enhances the interaction of viral proteins to the autophagosome receptor p62, promoting their autophagosome-dependent secretion. Additionally, ITCH disrupts the trafficking of the protease furin and the maturation of cathepsin L, thereby suppressing their activities in cleaving and destabilizing the viral spike protein. Furthermore, ITCH exhibits robust activation during the SARS-CoV-2 replication stage, and SARS-CoV-2 replication is significantly decreased by genetic or pharmacological inhibition of ITCH. These findings provide new insights into the mechanisms of the SARS-CoV-2 life cycle and identify a potential target for developing treatments for the virus-related diseases.

Indexed as

SARS-CoV-2Ubiquitin-Protein LigasesVirus ReplicationAnimalsCathepsin LChlorocebus aethiopsCOVID-19FurinHEK293 CellsHumansRepressor ProteinsSpike Glycoprotein, CoronavirusUbiquitinationCathepsin LFurinITCH protein, humanRepressor ProteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Ubiquitin-Protein Ligasescell biologyE3 ubiquitin protein ligaseenvelope proteinITCHmembrane proteinSARS-CoV-2spike proteinubiquitinviruses

Identifiers

PMID42213583
PMCPMC13221179

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.