ArticlePloS one2014
Chemical derivatives of a small molecule deubiquitinase inhibitor have antiviral activity against several RNA viruses.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 34 citations in OpenAlex.
- Quinazolinone based broad-spectrum antiviral molecules: design, synthesis, in silico studies and biological evaluation.Molecular diversity · 2026Article
- Chemical tools to define and manipulate interferon-inducible Ubl protease USP18.Nature communications · 2025Article
- Impaired K48-polyubiquitination downmodulates mouse norovirus propagation.Frontiers in cellular and infection microbiology · 2025Article
- Viral deubiquitinating proteases and the promising strategies of their inhibition.Virus research · 2024Review
- Review
- [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
- Norovirus Protease Structure and Antivirals Development.Viruses · 2021Review
- The Functional Deubiquitinating Enzymes in Control of Innate Antiviral Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- ISG15 overexpression compensates the defect of Crimean-Congo hemorrhagic fever virus polymerase bearing a protease-inactive ovarian tumor domain.PLoS neglected tropical diseases · 2020Article
- Norovirus antivirals: Where are we now?Medicinal research reviews · 2019Review
- TLR7 Agonists Display Potent Antiviral Effects against Norovirus Infection via Innate Stimulation.Antimicrobial agents and chemotherapy · 2018Article
- A compendium of small molecule direct-acting and host-targeting inhibitors as therapies against alphaviruses.The Journal of antimicrobial chemotherapy · 2017Review
- Inhibitors of Deubiquitinating Enzymes Block HIV-1 Replication and Augment the Presentation of Gag-Derived MHC-I Epitopes.Viruses · 2017Article
- Anti-infective Activity of 2-Cyano-3-Acrylamide Inhibitors with Improved Drug-Like Properties against Two Intracellular Pathogens.Antimicrobial agents and chemotherapy · 2016Article
- Review
- Antiviral targets of human noroviruses.Current opinion in virology · 2016Review
- Advances Toward a Norovirus Antiviral: From Classical Inhibitors to Lethal Mutagenesis.The Journal of infectious diseases · 2016Article
- Anti-norovirus therapeutics: a patent review (2010-2015).Expert opinion on therapeutic patents · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Most antiviral treatment options target the invading pathogen and unavoidably encounter loss of efficacy as the pathogen mutates to overcome replication restrictions. A good strategy for circumventing drug resistance, or for pathogens without treatment options, is to target host cell proteins that are utilized by viruses during infection. The small molecule WP1130 is a selective deubiquitinase inhibitor shown previously to successfully reduce replication of noroviruses and some other RNA viruses. In this study, we screened a library of 31 small molecule derivatives of WP1130 to identify compounds that retained the broad-spectrum antiviral activity of the parent compound in vitro but exhibited improved drug-like properties, particularly increased aqueous solubility. Seventeen compounds significantly reduced murine norovirus infection in murine macrophage RAW 264.7 cells, with four causing decreases in viral titers that were similar or slightly better than WP1130 (1.9 to 2.6 log scale). Antiviral activity was observed following pre-treatment and up to 1 hour postinfection in RAW 264.7 cells as well as in primary bone marrow-derived macrophages. Treatment of the human norovirus replicon system cell line with the same four compounds also decreased levels of Norwalk virus RNA. No significant cytotoxicity was observed at the working concentration of 5 µM for all compounds tested. In addition, the WP1130 derivatives maintained their broad-spectrum antiviral activity against other RNA viruses, Sindbis virus, LaCrosse virus, encephalomyocarditis virus, and Tulane virus. Thus, altering structural characteristics of WP1130 can maintain effective broad-spectrum antiviral activity while increasing aqueous solubility.
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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.