ArticleAntimicrobial agents and chemotherapy2016
A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity In Vitro.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Identifying antivirals against influenza PA endonuclease with machine learning-based activity prediction, DFT optimization, and molecular dynamics simulation.Molecular diversity · 2026Article
- Pharmacophores of Influenza Virus PA Endonuclease Inhibitors.Advances in experimental medicine and biology · 2026Review
- Multiple antiviral mechanisms of Ephedrae Herba and Cinnamomi Cortex against influenza: inhibition of entry and replication.Microbiology spectrum · 2025Article
- Article
- Biochemical characterization of mRNA capping enzyme from Faustovirus.RNA (New York, N.Y.) · 2023Article
- PA-E18G substitution in influenza A virus confers resistance to ZX-7101, a cap-dependent endonuclease inhibitor.Virologica Sinica · 2023Article
- Carboxylic Acid Isostere Derivatives of Hydroxypyridinones as Core Scaffolds for Influenza Endonuclease Inhibitors.ACS medicinal chemistry letters · 2023Article
- Pleiotropic Effects of Influenza H1, H3, and B Baloxavir-Resistant Substitutions on Replication, Sensitivity to Baloxavir, and Interferon Expression.Antimicrobial agents and chemotherapy · 2022Article
- Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.Acta pharmaceutica Sinica. B · 2022Review
- Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor.Molecules (Basel, Switzerland) · 2021Article
- Inhibition of Influenza Virus Polymerase by Interfering with Its Protein-Protein Interactions.ACS infectious diseases · 2021Review
- Synthesis, inhibitory activity and oral dosing formulation of AV5124, the structural analogue of influenza virus endonuclease inhibitor baloxavir.The Journal of antimicrobial chemotherapy · 2021Article
- Photorelease of a metal-binding pharmacophore from a Ru(II) polypyridine complex.Dalton transactions (Cambridge, England : 2003) · 2021Article
- Structural insights into the substrate specificity of the endonuclease activity of the influenza virus cap-snatching mechanism.Nucleic acids research · 2021Article
- The antiviral effects of baloxavir marboxil against influenza A virus infection in ferrets.Influenza and other respiratory viruses · 2020Article
- High throughput virtual screening reveals SARS-CoV-2 multi-target binding natural compounds to lead instant therapy for COVID-19 treatment.International journal of biological macromolecules · 2020Article
- Review
- Alternative Experimental Models for Studying Influenza Proteins, Host-Virus Interactions and Anti-Influenza Drugs.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference.Antiviral research · 2019Review
- Pharmacophore-based design of novel 3-hydroxypyrimidine-2,4-dione subtypes as inhibitors of HIV reverse transcriptase-associated RNase H: Tolerance of a nonflexible linker.European journal of medicinal chemistry · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Antiviral drugs are important in preventing and controlling influenza, particularly when vaccines are ineffective or unavailable. A single class of antiviral drugs, the neuraminidase inhibitors (NAIs), is recommended for treating influenza. The limited therapeutic options and the potential risk of antiviral resistance are driving the search for additional small-molecule inhibitors that act on influenza virus proteins. The acid polymerase (PA) of influenza viruses is a promising target for new antivirals because of its essential role in initiating virus transcription. Here, we characterized a novel compound, RO-7, identified as a putative PA endonuclease inhibitor. RO-7 was effective when added before the cessation of genome replication, reduced polymerase activity in cell-free systems, and decreased relative amounts of viral mRNA and genomic RNA during influenza virus infection. RO-7 specifically inhibited the ability of the PA endonuclease domain to cleave a nucleic acid substrate. RO-7 also inhibited influenza A viruses (seasonal and 2009 pandemic H1N1 and seasonal H3N2) and B viruses (Yamagata and Victoria lineages), zoonotic viruses (H5N1, H7N9, and H9N2), and NAI-resistant variants in plaque reduction, yield reduction, and cell viability assays in Madin-Darby canine kidney (MDCK) cells with nanomolar to submicromolar 50% effective concentrations (EC50s), low toxicity, and favorable selective indices. RO-7 also inhibited influenza virus replication in primary normal human bronchial epithelial cells. Overall, RO-7 exhibits broad-spectrum activity against influenza A and B viruses in multiple in vitro assays, supporting its further characterization and development as a potential antiviral agent for treating influenza.
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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.