ArticleScientific reports2017
Structural basis for therapeutic inhibition of influenza A polymerase PB2 subunit.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Parameterization of the PA Endonuclease Bimetallic Center Reveals the Dynamics of Clinically Relevant Mutations.Journal of chemical theory and computation · 2026Article
- A Structural View of Influenza Virus Ribonucleoprotein Complex and Its Functions.Microorganisms · 2026Review
- Anti-influenza drugs targeting trimeric RNA polymerase complex: From development to clinics.Acta pharmaceutica Sinica. B · 2026Review
- Computational Structural Analysis Predicts Host-Range Promiscuity and Antiviral Resistance in North American H5N1 Lineages.Computational and structural biotechnology journal · 2026Article
- Investigating Pb2 CAP-binding domain inhibitors from marine bacteria for targeting the influenza A H5N1.PloS one · 2025Article
- Aptamers: precision tools for diagnosing and treating infectious diseases.Frontiers in cellular and infection microbiology · 2024Review
- Design, Synthesis, Biological Evaluation, and Molecular Dynamics Simulation of Influenza Polymerase PB2 Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- 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
- Susceptibility of widely diverse influenza a viruses to PB2 polymerase inhibitor pimodivir.Antiviral research · 2021Article
- Design, Synthesis, and Biological Evaluation of Novel Indoles Targeting the Influenza PB2 Cap Binding Region.Journal of medicinal chemistry · 2019Article
- Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Influenza virus uses a unique mechanism to initiate viral transcription named cap-snatching. The PB2 subunit of the viral heterotrimeric RNA polymerase binds the cap structure of cellular pre-mRNA to promote its cleavage by the PA subunit. The resulting 11-13 capped oligomer is used by the PB1 polymerase subunit to initiate transcription of viral proteins. VX-787 is an inhibitor of the influenza A virus pre-mRNA cap-binding protein PB2. This clinical stage compound was shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery. However, the binding of this molecule in the context of an extended form of the PB2 subunit has remained elusive. Here we generated a collection of PB2 truncations to identify a PB2 protein representative of its structure in the viral heterotrimeric protein. We present the crystal structure of VX-787 bound to a PB2 construct that recapitulates VX-787's biological antiviral activity in vitro. This co-structure reveals more extensive interactions than previously identified and provides insight into the observed resistance profile, affinity, binding kinetics, and conformational rearrangements induced by VX-787.
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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.