ArticleJournal of medicinal chemistry2016
Fragment-Based Identification of Influenza Endonuclease Inhibitors.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 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
30 citing papers in PubMed, 65 citations in OpenAlex.
- Identifying antivirals against influenza PA endonuclease with machine learning-based activity prediction, DFT optimization, and molecular dynamics simulation.Molecular diversity · 2026Article
- Substituent size versus metal binding of inhibitors with variants of influenza endonuclease.Journal of inorganic biochemistry · 2026Article
- Pharmacophores of Influenza Virus PA Endonuclease Inhibitors.Advances in experimental medicine and biology · 2026Review
- A Susceptible Cell-Selective Delivery (SCSD) of mRNA-Encoded Cas13d Against Influenza Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A novel compound to overcome influenza drug resistance in endonuclease inhibitors.Molecular diversity · 2024Article
- Outlining recent updates on influenza therapeutics and vaccines: A comprehensive review.Vaccine: X · 2024Review
- Structural Studies of Inhibitors with Clinically Relevant Influenza Endonuclease Variants.Biochemistry · 2024Article
- Emerging drug design strategies in anti-influenza drug discovery.Acta pharmaceutica Sinica. B · 2023Review
- Article
- T-705-Derived Prodrugs Show High Antiviral Efficacies against a Broad Range of Influenza A Viruses with Synergistic Effects When Combined with Oseltamivir.Pharmaceutics · 2023Article
- Fragment Merging Using a Graph Database Samples Different Catalogue Space than Similarity Search.Journal of chemical information and modeling · 2023Article
- Carboxylic Acid Isostere Derivatives of Hydroxypyridinones as Core Scaffolds for Influenza Endonuclease Inhibitors.ACS medicinal chemistry letters · 2023Article
- Metabolomics Highlights Different Life History Strategies of White and Brown Rot Wood-Degrading Fungi.mSphere · 2022Article
- Discovery of Novel 3-Hydroxyquinazoline-2,4(1International journal of molecular sciences · 2022Article
- Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.Acta pharmaceutica Sinica. B · 2022Review
- Salicylate metal-binding isosteres as fragments for metalloenzyme inhibition.Chemical science · 2022Article
- Recent Advances of Pyridinone in Medicinal Chemistry.Frontiers in chemistry · 2022Review
- Exploration of the 2,3-dihydroisoindole pharmacophore for inhibition of the influenza virus PA endonuclease.Bioorganic chemistry · 2021Article
- Synthesis and In Vitro Evaluation of C-7 and C-8 Luteolin Derivatives as Influenza Endonuclease Inhibitors.International journal of molecular sciences · 2021Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The influenza virus is responsible for millions of cases of severe illness annually. Yearly variance in the effectiveness of vaccination, coupled with emerging drug resistance, necessitates the development of new drugs to treat influenza infections. One attractive target is the RNA-dependent RNA polymerase PA subunit. Herein we report the development of inhibitors of influenza PA endonuclease derived from lead compounds identified from a metal-binding pharmacophore (MBP) library screen. Pyromeconic acid and derivatives thereof were found to be potent inhibitors of endonuclease. Guided by modeling and previously reported structural data, several sublibraries of molecules were elaborated from the MBP hits. Structure-activity relationships were established, and more potent molecules were designed and synthesized using fragment growth and fragment merging strategies. This approach ultimately resulted in the development of a lead compound with an IC50 value of 14 nM, which displayed an EC50 value of 2.1 μM against H1N1 influenza virus in MDCK cells.
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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.