ArticleProceedings of the National Academy of Sciences of the United States of America2020
An influenza A hemagglutinin small-molecule fusion inhibitor identified by a new high-throughput fluorescence polarization screen.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed.
- Triazavirin And Its Derivatives Act As Influenza A Virus Fusion Inhibitors.Pharmaceutical research · 2026Article
- FlyTomo: a streamlined software for on-the-fly cryo-ET data processing and diagnosis.Nature communications · 2026Article
- Structural basis for distinct protective mechanisms of IGHV3-23 antibodies targeting influenza hemagglutinin stem.Nature communications · 2026Article
- A plant gallotannin pentagalloyl d-glucose elicits antiviral activity against influenza A and B viruses through multi-targeting mechanisms.Archives of virology · 2026Article
- Review
- Direct-to-Biology: Streamlining the Path From Chemistry to Biology in Drug Discovery.ChemMedChem · 2026Review
- Article
- Mechanistic insights into the small-molecule inhibition of influenza A virus entry.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multiple antiviral mechanisms of Ephedrae Herba and Cinnamomi Cortex against influenza: inhibition of entry and replication.Microbiology spectrum · 2025Article
- Mining Druggable Sites in Influenza A Hemagglutinin: Binding of the Pinanamine-Based Inhibitor M090.ACS medicinal chemistry letters · 2025Article
- Small Molecule Influenza Virus Fusion Inhibitors Targeting Viral Hemagglutinin: Chemical Insights and Antiviral Evaluation.Mini reviews in medicinal chemistry · 2025Review
- Article
- An aptamer-guided fluorescence polarisation platform for extracellular vesicle liquid biopsy.Journal of extracellular vesicles · 2024Article
- A Fluorogenic Pseudoinfection Assay to Probe Transfer and Distribution of Influenza Viral Contents to Target Vesicles.Analytical chemistry · 2024Article
- Ultrapotent influenza hemagglutinin fusion inhibitors developed through SuFEx-enabled high-throughput medicinal chemistry.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Glycomimetics for the inhibition and modulation of lectins.Chemical Society reviews · 2023Review
- Review
- Protective neutralizing epitopes in SARS-CoV-2.Immunological reviews · 2022Review
- Broad-Spectrum Activity of Small Molecules Acting against Influenza a Virus: Biological and Computational Studies.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Treatment of Respiratory Viral Coinfections.Epidemiologia (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Influenza hemagglutinin (HA) glycoprotein is the primary surface antigen targeted by the host immune response and a focus for development of novel vaccines, broadly neutralizing antibodies (bnAbs), and therapeutics. HA enables viral entry into host cells via receptor binding and membrane fusion and is a validated target for drug discovery. However, to date, only a very few bona fide small molecules have been reported against the HA. To identity new antiviral lead candidates against the highly conserved fusion machinery in the HA stem, we synthesized a fluorescence-polarization probe based on a recently described neutralizing cyclic peptide P7 derived from the complementarity-determining region loops of human bnAbs FI6v3 and CR9114 against the HA stem. We then designed a robust binding assay compatible with high-throughput screening to identify molecules with low micromolar to nanomolar affinity to influenza A group 1 HAs. Our simple, low-cost, and efficient in vitro assay was used to screen H1/Puerto Rico/8/1934 (H1/PR8) HA trimer against ∼72,000 compounds. The crystal structure of H1/PR8 HA in complex with our best hit compound F0045(S) confirmed that it binds to pockets in the HA stem similar to bnAbs FI6v3 and CR9114, cyclic peptide P7, and small-molecule inhibitor JNJ4796. F0045 is enantioselective against a panel of group 1 HAs and F0045(S) exhibits in vitro neutralization activity against multiple H1N1 and H5N1 strains. Our assay, compound characterization, and small-molecule candidate should further stimulate the discovery and development of new compounds with unique chemical scaffolds and enhanced influenza antiviral capabilities.
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Registered trials
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