ArticleACS chemical biology2012
Identification of influenza endonuclease inhibitors using a novel fluorescence polarization assay.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 82 citations in OpenAlex.
- Pharmacophores of Influenza Virus PA Endonuclease Inhibitors.Advances in experimental medicine and biology · 2026Review
- From neuraminidase inhibitors to novel mechanisms: expanding therapeutic strategies against influenza.Frontiers in cellular and infection microbiology · 2026Review
- Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches.Cellular and molecular life sciences : CMLS · 2025Review
- Fluorescence-Polarization-Based Assaying of Lysozyme with Chitooligosaccharide Tracers.Biomolecules · 2024Article
- Carboxylic Acid Isostere Derivatives of Hydroxypyridinones as Core Scaffolds for Influenza Endonuclease Inhibitors.ACS medicinal chemistry letters · 2023Article
- Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.Acta pharmaceutica Sinica. B · 2022Review
- Enzymatic Assays to Explore Viral mRNA Capping Machinery.Chembiochem : a European journal of chemical biology · 2021Review
- A new G-triplex-based strategy for sensitivity enhancement of the detection of endonuclease activity and inhibition.RSC advances · 2021Article
- Investigation of Binding Affinity between Potential Antiviral Agents and PB2 Protein of Influenza A: Non-equilibrium Molecular Dynamics Simulation Approach.International journal of medical sciences · 2020Article
- Focusing on the Influenza Virus Polymerase Complex: Recent Progress in Drug Discovery and Assay Development.Current medicinal chemistry · 2019Review
- Protein-Structure Assisted Optimization of 4,5-Dihydroxypyrimidine-6-Carboxamide Inhibitors of Influenza Virus Endonuclease.Scientific reports · 2017Article
- Progress of small molecular inhibitors in the development of anti-influenza virus agents.Theranostics · 2017Review
- Article
- The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design.Medicinal research reviews · 2016Review
- A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro.Antimicrobial agents and chemotherapy · 2016Article
- Fragment-Based Identification of Influenza Endonuclease Inhibitors.Journal of medicinal chemistry · 2016Article
- Fluorescence polarization assays in high-throughput screening and drug discovery: a review.Methods and applications in fluorescence · 2016Article
- Stacking with No Planarity?ACS medicinal chemistry letters · 2016Article
- Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A novel small-molecule inhibitor of influenza A virus acts by suppressing PA endonuclease activity of the viral polymerase.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Influenza viruses have been responsible for the largest pandemics in the previous century. Although vaccination and prophylactic antiviral therapeutics are the primary defense against influenza virus, there is a pressing need to develop new antiviral agents to circumvent the limitations of current therapies. The endonuclease activity of the influenza virus PA(N) protein is essential for virus replication and is a promising target for novel anti-influenza drugs. To facilitate the discovery of endonuclease inhibitors, we have developed a high-throughput fluorescence polarization (FP) assay, utilizing a novel fluorescein-labeled compound (K(d) = 0.378 μM) and a PA(N) construct, to identify small molecules that bind to the PA(N) endonuclease active site. Several known 4-substituted 2,4-dioxobutanoic acid inhibitors with high and low affinities have been evaluated in this FP-based competitive binding assay, and there was a general correlation between binding and the reported inhibition of endonuclease activity. Additionally, we have demonstrated the utility of this assay for identifying endonuclease inhibitors in a small diverse targeted fragment library. These fragment hits were used to build a follow-up library that that led to new active compounds that demonstrate FP binding and anti-influenza activities in plaque inhibition assays. The assay offers significant advantages over previously reported assays and is suitable for high-throughput and fragment-based screening studies. Additionally the demonstration of the applicability of a mechanism-based "targeted fragment" library supports the general potential of this novel approach for other enzyme targets. These results serve as a sound foundation for the development of new therapeutic leads targeting influenza endonuclease.
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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.