ArticleProceedings of the National Academy of Sciences of the United States of America2012
Small molecule inhibitors of influenza A and B viruses that act by disrupting subunit interactions of the viral polymerase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 127 citations in OpenAlex.
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- From neuraminidase inhibitors to novel mechanisms: expanding therapeutic strategies against influenza.Frontiers in cellular and infection microbiology · 2026Review
- Design, synthesis and biological evaluation of a novel class of indazole-containing compounds with potent anti-influenza activities targeting the PA-PB1 interface.Acta pharmaceutica Sinica. B · 2025Article
- Antiviral strategies against influenza virus: an update on approved and innovative therapeutic approaches.Cellular and molecular life sciences : CMLS · 2025Review
- New dengue virus inhibitors targeting NS3-NS5 interaction identified byFrontiers in microbiology · 2025Article
- Exploring a New Generation of Pyrimidine and Pyridine Derivatives as Anti-Influenza Agents Targeting the Polymerase PA-PB1 Subunits Interaction.Pharmaceutics · 2024Article
- Inhibition of bacterial RNA polymerase function and protein-protein interactions: a promising approach for next-generation antibacterial therapeutics.RSC medicinal chemistry · 2024Review
- Outlining recent updates on influenza therapeutics and vaccines: A comprehensive review.Vaccine: X · 2024Review
- Small-Molecule Inhibitor of Flaviviral NS3-NS5 Interaction with Broad-Spectrum Activity and EfficacymBio · 2023Article
- Upregulation of galectin-3 in influenza A virus infection promotes viral RNA synthesis through its association with viral PA protein.Journal of biomedical science · 2023Article
- Development and characterization of an inducible assay system to measure Zika virus capsid interactions.Journal of medical virology · 2022Article
- Discovery of novel SARS-CoV-2 inhibitors targeting the main protease MAntiviral research · 2022Article
- Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.Acta pharmaceutica Sinica. B · 2022Review
- AnBio-protocol · 2022Article
- Inhibition of Influenza Virus Polymerase by Interfering with Its Protein-Protein Interactions.ACS infectious diseases · 2021Review
- A novel piperazine derivative that targets hepatitis B surface antigen effectively inhibits tenofovir resistant hepatitis B virus.Scientific reports · 2021Article
- Article
- Synthesis and characterization of 1,2,4-triazolo[1,5-a]pyrimidine-2-carboxamide-based compounds targeting the PA-PB1 interface of influenza A virus polymerase.European journal of medicinal chemistry · 2021Article
- Discovery of Influenza Polymerase PA-PB1 Interaction Inhibitors Using anACS chemical biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Influenza viruses are the cause of yearly epidemics and occasional pandemics that represent a significant challenge to public health. Current control strategies are imperfect and there is an unmet need for new antiviral therapies. Here, we report the identification of small molecule compounds able to effectively and specifically inhibit growth of influenza A and B viruses in cultured cells through targeting an assembly interface of the viral RNA-dependent RNA polymerase. Using an existing crystal structure of the primary protein-protein interface between the PB1 and PA subunits of the influenza A virus polymerase, we conducted an in silico screen to identify potential small molecule inhibitors. Selected compounds were then screened for their ability to inhibit the interaction between PB1 and PA in vitro using an ELISA-based assay and in cells, to inhibit nuclear import of a binary PB1-PA complex as well as transcription by the full viral ribonucleoprotein complex. Two compounds emerged as effective inhibitors with IC(50) values in the low micromolar range and negligible cytotoxicity. Of these, one compound also acted as a potent replication inhibitor of a variety of influenza A virus strains in Madin-Darby canine kidney (MDCK) cells, including H3N2 and H1N1 seasonal and 2009 pandemic strains. Importantly, this included an oseltamivir-resistant isolate. Furthermore, potent inhibition of influenza B viruses but not other RNA or DNA viruses was seen. Overall, these compounds provide a foundation for the development of a new generation of therapeutic agents exhibiting high specificity to influenza A and B viruses.
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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.