ArticleAntimicrobial agents and chemotherapy2014
Nonnucleoside inhibitors of norovirus RNA polymerase: scaffolds for rational drug design.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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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.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Activity and cryo-EM structure of the polymerase domain of the human norovirus ProPol precursor.Journal of virology · 2024Article
- Current and Future Antiviral Strategies to Tackle Gastrointestinal Viral Infections.Microorganisms · 2021Review
- Predicting New Anti-Norovirus Inhibitor With the Help of Machine Learning Algorithms and Molecular Dynamics Simulation-Based Model.Frontiers in chemistry · 2021Article
- A new antiviral scaffold for human norovirus identified with computer-aided approaches on the viral polymerase.Scientific reports · 2019Article
- Antiviral Candidates for Treating Hepatitis E Virus Infection.Antimicrobial agents and chemotherapy · 2019Article
- The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses.Viruses · 2019Article
- Norovirus antivirals: Where are we now?Medicinal research reviews · 2019Review
- Targeting the Viral Polymerase of Diarrhea-Causing Viruses as a Strategy to Develop a Single Broad-Spectrum Antiviral Therapy.Viruses · 2019Review
- Calicivirus RNA-Dependent RNA Polymerases: Evolution, Structure, Protein Dynamics, and Function.Frontiers in microbiology · 2019Review
- Article
- TLR7 Agonists Display Potent Antiviral Effects against Norovirus Infection via Innate Stimulation.Antimicrobial agents and chemotherapy · 2018Article
- In silico screening for human norovirus antivirals reveals a novel non-nucleoside inhibitor of the viral polymerase.Scientific reports · 2018Article
- Article
- Structure(s), function(s), and inhibition of the RNA-dependent RNA polymerase of noroviruses.Virus research · 2017Review
- RNA Sequencing of Murine Norovirus-Infected Cells Reveals Transcriptional Alteration of Genes Important to Viral Recognition and Antigen Presentation.Frontiers in immunology · 2017Article
- Current tools for norovirus drug discovery.Expert opinion on drug discovery · 2016Review
- Antiviral targets of human noroviruses.Current opinion in virology · 2016Review
- Article
- 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
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide, causing over 200,000 deaths a year. NoV is nonenveloped, with a single-stranded RNA genome, and is primarily transmitted person to person. The viral RNA-dependent RNA polymerase (RdRp) is critical for the production of genomic and subgenomic RNA and is therefore a prime target for antiviral therapies. Using high-throughput screening, nearly 20,000 "lead-like" compounds were tested for inhibitory activity against the NoV genogroup II, genotype 4 (GII.4) RdRp. The four most potent hits demonstrated half-maximal inhibitory concentrations (IC50s) between 5.0 μM and 9.8 μM against the target RdRp. Compounds NIC02 and NIC04 revealed a mixed mode of inhibition, while NIC10 and NIC12 were uncompetitive RdRp inhibitors. When examined using enzymes from related viruses, NIC02 demonstrated broad inhibitory activity while NIC04 was the most specific GII.4 RdRp inhibitor. The antiviral activity was examined using available NoV cell culture models; the GI.1 replicon and the infectious GV.1 murine norovirus (MNV). NIC02 and NIC04 inhibited the replication of the GI.1 replicon, with 50% effective concentrations (EC50s) of 30.1 μM and 71.1 μM, respectively, while NIC10 and NIC12 had no observable effect on the NoV GI.1 replicon. In the MNV model, NIC02 reduced plaque numbers, size, and viral RNA levels in a dose-dependent manner (EC50s between 2.3 μM and 4.8 μM). The remaining three compounds also reduced MNV replication, although with higher EC50s, ranging from 32 μM to 38 μM. In summary, we have identified novel nonnucleoside inhibitor scaffolds that will provide a starting framework for the development and future optimization of targeted antivirals against NoV.
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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.