ArticleBiochemistry2010
Functional studies and modeling of pore-lining residue mutants of the influenza a virus M2 ion channel.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed.
- Active pH Modulation by Proton Channel-Peptide Nucleic Acid Complex for Effective siRNA Endosomal Escape.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- The crucial role of intercellular calcium wave propagation triggered by influenza A virus in promoting infection.Cell communication and signaling : CCS · 2025Article
- Molecular biophysics and inhibition mechanism of influenza virus A M2 viroporin by adamantane-based drugs - Challenges in designing antiviral agents.Journal of structural biology: X · 2025Article
- Evolving Dynamics of Whole-Genome Influenza A/H3N2 Viruses Isolated in Cameroon.Advances in virology · 2025Article
- Activation of the Influenza B M2 Proton Channel (BM2).Biochemistry · 2024Article
- Activation of the influenza B M2 proton channel (BM2).bioRxiv : the preprint server for biology · 2024Article
- Influenza Viruses: Harnessing the Crucial Role of the M2 Ion-Channel and Neuraminidase toward Inhibitor Design.Molecules (Basel, Switzerland) · 2021Review
- Investigation of the Drug Resistance Mechanism of M2-S31N Channel Blockers through Biomolecular Simulations and Viral Passage Experiments.ACS pharmacology & translational science · 2020Article
- Put a cork in it: Plugging the M2 viral ion channel to sink influenza.Antiviral research · 2020Review
- Article
- Atomic structures of closed and open influenza B M2 proton channel reveal the conduction mechanism.Nature structural & molecular biology · 2020Article
- M2e-based universal influenza vaccines: a historical overview and new approaches to development.Journal of biomedical science · 2019Review
- The L46P mutant confers a novel allosteric mechanism of resistance toward the influenza A virus M2 S31N proton channel blockers.Molecular pharmacology · 2019Article
- X-ray Crystal Structure of the Influenza A M2 Proton Channel S31N Mutant in Two Conformational States: An Open and Shut Case.Journal of the American Chemical Society · 2019Article
- The Transmembrane Conformation of the Influenza B Virus M2 Protein in Lipid Bilayers.Scientific reports · 2019Article
- Inhibitors of the M2 Proton Channel Engage and Disrupt Transmembrane Networks of Hydrogen-Bonded Waters.Journal of the American Chemical Society · 2018Article
- Profiling the in vitro drug-resistance mechanism of influenza A viruses towards the AM2-S31N proton channel blockers.Antiviral research · 2018Article
- Transport-Relevant Protein Conformational Dynamics and Water Dynamics on Multiple Time Scales in an Archetypal Proton Channel: Insights from Solid-State NMR.Journal of the American Chemical Society · 2018Article
- XFEL structures of the influenza M2 proton channel: Room temperature water networks and insights into proton conduction.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Influenza A Virus M2 Protein: Roles from Ingress to Egress.International journal of molecular sciences · 2017Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
The A/M2 protein of influenza A virus forms a tetrameric proton-selective pH-gated ion channel. The H(37)xxxW(41) motif located in the channel pore is responsible for its gating and proton selectivity. Channel activation most likely involves protonation of the H37 residues, while the conductive state of the channel is characterized by two or three charged His residues in a tetrad. A/M2 channel activity is inhibited by the antiviral drug amantadine. Although a large number of functional amantadine-resistant mutants of A/M2 have been observed in vitro, only a few are observed in highly transmissible viruses in the presence or absence of amantadine. We therefore examined 49 point mutants of the pore-lining residues, representing both natural and nonnatural variants. Their ion selectivity, amantadine sensitivity, specific activity, and pH-dependent conductance were measured in Xenopus oocytes. These measurements showed how variations in the sequence lead to variations in the proton conduction. The results are consistent with a multistep mechanism that allows the protein to fine-tune its pH-rate profile over a wide range of proton concentrations, hypothesized to arise from different protonation states of the H37 tetrad. Mutations that give native-like conductance at low pH as well as minimal leakage current at pH 7.0 were surprisingly rare. Moreover, the results are consistent with a location of the amantadine-binding site inside the channel pore. These findings have helped to define the set of functionally fit mutants that should be targeted when considering the design of novel drugs that inhibit amantadine-resistant strains of influenza A virus.
Indexed as
Identifiers
What OpenQuestion holds
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.