ArticlePLoS pathogens2012
Antiviral activity of a small molecule deubiquitinase inhibitor occurs via induction of the unfolded protein response.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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.
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.
Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
- Quinazolinone based broad-spectrum antiviral molecules: design, synthesis, in silico studies and biological evaluation.Molecular diversity · 2026Article
- The deubiquitinase inhibitor WP1130 drives nuclear aggregation and reactivation of mutant p53 for selective cancer cell targeting.The FEBS journal · 2025Article
- Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy.PLoS pathogens · 2025Article
- Chemical tools to define and manipulate interferon-inducible Ubl protease USP18.Nature communications · 2025Article
- Review
- USP14 inhibition promotes DNA damage repair and represses ovarian granulosa cell senescence in premature ovarian insufficiency.Journal of translational medicine · 2024Article
- Article
- Viral deubiquitinating proteases and the promising strategies of their inhibition.Virus research · 2024Review
- Article
- [WP1130 relieves septic shock in mice by inhibiting NLRP3 inflammasome activation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Article
- The Role of Deubiquitinases in Virus Replication and Host Innate Immune Response.Frontiers in microbiology · 2022Review
- Factors affecting RIG-I-Like receptors activation - New research direction for viral hemorrhagic fevers.Frontiers in immunology · 2022Review
- Norovirus Protease Structure and Antivirals Development.Viruses · 2021Review
- Role of Virally-Encoded Deubiquitinating Enzymes in Regulation of the Virus Life Cycle.International journal of molecular sciences · 2021Review
- USP14: Structure, Function, and Target Inhibition.Frontiers in pharmacology · 2021Review
- The Functional Deubiquitinating Enzymes in Control of Innate Antiviral Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation.International journal of molecular sciences · 2020Review
- Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development.Signal transduction and targeted therapy · 2020Review
- Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape.PLoS pathogens · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Ubiquitin (Ub) is a vital regulatory component in various cellular processes, including cellular responses to viral infection. As obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (Ub) cycle to their advantage by encoding Ub-modifying proteins including deubiquitinases (DUBs). However, how cellular DUBs modulate specific viral infections, such as norovirus, is poorly understood. To examine the role of DUBs during norovirus infection, we used WP1130, a small molecule inhibitor of a subset of cellular DUBs. Replication of murine norovirus in murine macrophages and the human norovirus Norwalk virus in a replicon system were significantly inhibited by WP1130. Chemical proteomics identified the cellular DUB USP14 as a target of WP1130 in murine macrophages, and pharmacologic inhibition or siRNA-mediated knockdown of USP14 inhibited murine norovirus infection. USP14 is a proteasome-associated DUB that also binds to inositol-requiring enzyme 1 (IRE1), a critical mediator of the unfolded protein response (UPR). WP1130 treatment of murine macrophages did not alter proteasome activity but activated the X-box binding protein-1 (XBP-1) through an IRE1-dependent mechanism. In addition, WP1130 treatment or induction of the UPR also reduced infection of other RNA viruses including encephalomyocarditis virus, Sindbis virus, and La Crosse virus but not vesicular stomatitis virus. Pharmacologic inhibition of the IRE1 endonuclease activity partially rescued the antiviral effect of WP1130. Taken together, our studies support a model whereby induction of the UPR through cellular DUB inhibition blocks specific viral infections, and suggest that cellular DUBs and the UPR represent novel targets for future development of broad spectrum antiviral therapies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.