ArticleNucleic acids research2018
Capped RNA primer binding to influenza polymerase and implications for the mechanism of cap-binding inhibitors.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 56 citations in OpenAlex.
- Preclinical characterization of HEC116094, an oral inhibitor of the influenza A virus polymerase PB2 subunit.Emerging microbes & infections · 2026Article
- Anti-influenza drugs targeting trimeric RNA polymerase complex: From development to clinics.Acta pharmaceutica Sinica. B · 2026Review
- The 5'-end segment-specific noncoding region of influenza A virus regulates both competitive multi-segment RNA transcription and selective genome packaging during infection.Journal of virology · 2025Article
- Conformational Dynamics of Influenza A Virus Ribonucleoprotein Complexes during RNA Synthesis.ACS nano · 2024Article
- Review
- The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome.Nature communications · 2024Article
- Article
- Revisiting Viral RNA-Dependent RNA Polymerases: Insights from Recent Structural Studies.Viruses · 2022Review
- Type B and type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD.PLoS pathogens · 2022Article
- Contemporary medicinal chemistry strategies for the discovery and optimization of influenza inhibitors targeting vRNP constituent proteins.Acta pharmaceutica Sinica. B · 2022Review
- Virtual Screening and Molecular Dynamics Simulation Study of Influenza Polymerase PB2 Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Structure and Function of Influenza Polymerase.Cold Spring Harbor perspectives in medicine · 2021Review
- Comprehensive Profiling of Mutations to Influenza Virus PB2 That Confer Resistance to the Cap-Binding Inhibitor Pimodivir.Viruses · 2021Article
- Inhibition of Influenza Virus Polymerase by Interfering with Its Protein-Protein Interactions.ACS infectious diseases · 2021Review
- Structural insights into RNA polymerases of negative-sense RNA viruses.Nature reviews. Microbiology · 2021Review
- Structural insights into the substrate specificity of the endonuclease activity of the influenza virus cap-snatching mechanism.Nucleic acids research · 2021Article
- Viral Subpopulation Screening Guides in Designing a High Interferon-Inducing Live Attenuated Influenza Vaccine by Targeting Rare Mutations in NS1 and PB2 Proteins.Journal of virology · 2020Article
- Structure and Function of the Influenza Virus Transcription and Replication Machinery.Cold Spring Harbor perspectives in medicine · 2020Review
- Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication.Scientific reports · 2020Article
- Interaction between influenza A virus nucleoprotein and PB2 cap-binding domain is mediated by RNA.PloS one · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Influenza polymerase uses short capped primers snatched from nascent Pol II transcripts to initiate transcription of viral mRNAs. Here we describe crystal structures of influenza A and B polymerase bound to a capped primer in a configuration consistent with transcription initiation ('priming state') and show by functional assays that conserved residues from both the PB2 midlink and cap-binding domains are important for positioning the capped RNA. In particular, mutation of PB2 Arg264, which interacts with the triphosphate linkage in the cap, significantly and specifically decreases cap-dependent transcription. We also compare the configuration of the midlink and cap-binding domains in the priming state with their very different relative arrangement (called the 'apo' state) in structures where the potent cap-binding inhibitor VX-787, or a close analogue, is bound. In the 'apo' state the inhibitor makes additional interactions to the midlink domain that increases its affinity beyond that to the cap-binding domain alone. The comparison suggests that the mechanism of resistance of certain mutations that allow virus to escape from VX-787, notably PB2 N510T, can only be rationalized if VX-787 has a dual mode of action, direct inhibition of capped RNA binding as well as stabilization of the transcriptionally inactive 'apo' state.
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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.