ArticleProceedings of the National Academy of Sciences of the United States of America2010
Coexistence of two adamantane binding sites in the influenza A M2 ion channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 70 citations in OpenAlex.
- Adamantane-based inhibitors of the influenza A M2 proton channel: structure-based design, biological evaluation, and synthetic approaches.RSC medicinal chemistry · 2026Review
- Review
- Bat Influenza M2 Shows Functions Similar to Those of Classical Influenza A Viruses.Pathogens (Basel, Switzerland) · 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
- A Review on cLF36, a Novel Recombinant Antimicrobial Peptide-Derived Camel Lactoferrin.Probiotics and antimicrobial proteins · 2024Review
- Bicyclic Isoxazoline Derivatives: Synthesis and Evaluation of Biological Activity.Molecules (Basel, Switzerland) · 2022Article
- Influenza AM2 Channel Oligomerization Is Sensitive to Its Chemical Environment.Analytical chemistry · 2021Article
- From Acid Activation Mechanisms of Proton Conduction to Design of Inhibitors of the M2 Proton Channel of Influenza A Virus.Frontiers in molecular biosciences · 2021Review
- Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza.PLoS pathogens · 2020Article
- Put a cork in it: Plugging the M2 viral ion channel to sink influenza.Antiviral research · 2020Review
- M2 amphipathic helices facilitate pH-dependent conformational transition in influenza A virus.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Salinomycin Inhibits Influenza Virus Infection by Disrupting Endosomal Acidification and Viral Matrix Protein 2 Function.Journal of virology · 2018Article
- Unraveling the Binding, Proton Blockage, and Inhibition of Influenza M2 WT and S31N by Rimantadine Variants.ACS medicinal chemistry letters · 2018Article
- Structural Basis for Asymmetric Conductance of the Influenza M2 Proton Channel Investigated by Solid-State NMR Spectroscopy.Journal of molecular biology · 2017Article
- Binding and Proton Blockage by Amantadine Variants of the Influenza M2Journal of medicinal chemistry · 2017Article
- Membrane Protein Structure, Function, and Dynamics: a Perspective from Experiments and Theory.The Journal of membrane biology · 2015Review
- Hydrogen-bonded water molecules in the M2 channel of the influenza A virus guide the binding preferences of ammonium-based inhibitors.The journal of physical chemistry. B · 2015Article
- Computational Docking Study of p7 Ion Channel from HCV Genotype 3 and Genotype 4 and Its Interaction with Natural Compounds.PloS one · 2015Article
- Verdinexor, a novel selective inhibitor of nuclear export, reduces influenza a virus replication in vitro and in vivo.Journal of virology · 2014Article
- In depth analysis on the binding sites of adamantane derivatives in HCV (hepatitis C virus) p7 channel based on the NMR structure.PloS one · 2014Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The influenza A virus contains a proton-selective ion channel (M2) that is the target of the adamantane family of drug inhibitors. Two recently published studies relating to adamantane binding of the M2 ion channel using X-ray crystallography and solution NMR have reignited interest in the potential use of adamantanes in combating the spread of influenza A. However, these two studies propose different binding sites for the adamantane drugs with the X-ray M2/amantadine structure favoring an ion channel pore-binding model and the solution NMR M2/rimantadine structure suggesting the existence of a lipid-facing binding pocket. We conducted a series of surface plasmon resonance (SPR) experiments designed to accurately measure the affinity of amantadine and rimantadine to M2 ion channels embedded in 1,2-dimyristoyl-sn-glycero-phosphocholine (DMPC) liposomes. We find that this class of drug is capable of binding M2 with two different affinities in the order of 10(-4) and 10(-7) M, suggesting that both proposed binding sites are feasible. Furthermore, by examining drug binding to M2 mutant constructs (V27A, S31N, and D44A), it was possible to probe the location of the two binding sites. We show that a high-affinity binding site corresponds to the M2 ion channel pore whereas the secondary, low-affinity binding site can be attributed to the lipid face of the pore. These SPR results are in excellent agreement with the most recent solid-state NMR study of amantadine-bound M2 in lipid bilayers and provide independent support that the ion channel pore-binding site is responsible for the pharmacological activity elicited by the adamantane drugs.
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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.