ArticleNature2010
Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 332 papers, 1 of them a synthesis that pooled it.
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
332 citing papers in PubMed, 1 synthesis or guideline pooled it, 629 citations in OpenAlex.
- Antiglycoxidative properties of amantadine - a systematic review and comprehensive in vitro study.Journal of enzyme inhibition and medicinal chemistry · 2023Pooled it
- Targeted degradation of Influenza a virus nucleoprotein via aptamer-based PROTACs for antiviral therapy.Virulence · 2026Article
- Adamantane-based inhibitors of the influenza A M2 proton channel: structure-based design, biological evaluation, and synthetic approaches.RSC medicinal chemistry · 2026Review
- Engineered Channel Asymmetry Extends Hydrogen-Bonding Networks for Proton Conduction.bioRxiv : the preprint server for biology · 2026Article
- Advances in understanding the Clostridial spore inner membrane.Archives of microbiology · 2026Review
- Anti-influenza drugs targeting trimeric RNA polymerase complex: From development to clinics.Acta pharmaceutica Sinica. B · 2026Review
- Diamond rotors for high magic angle spinning frequencies.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2025Article
- Structural Transition from Closed to Open for the Influenza A M2 Proton Channel as Observed by Proton-Detected Solid-State NMR.Journal of the American Chemical Society · 2025Article
- Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins.Viruses · 2025Review
- 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
- Solid-state NMR protocols for unveiling dynamics and (drug) interactions of membrane-bound proteins.Protein science : a publication of the Protein Society · 2025Article
- Solid-State NMR of Virus Membrane Proteins.Accounts of chemical research · 2025Article
- Conformational Analysis of UniformlyMolecules (Basel, Switzerland) · 2025Article
- The Role of Cholesterol in M2 Clustering and Viral Budding Explained.Journal of chemical theory and computation · 2025Article
- Dipolar Recoupling in Rotating Solids.Chemical reviews · 2024Review
- Oligomeric State and Drug Binding of the SARS-CoV-2 Envelope Protein Are Sensitive to the Ectodomain.Journal of the American Chemical Society · 2024Article
- The plant rhabdovirus viroporin P9 facilitates insect-mediated virus transmission in barley.The Plant cell · 2024Article
- Computational investigation in inhibitory effects of amantadine on classical swine fever virus p7 ion channel activity.Scientific reports · 2024Article
- Structure and dynamics of the proton-selective histidine and the gating tryptophan in an inward rectifying hybrid influenza B and A virus M2 proton channel.Physical chemistry chemical physics : PCCP · 2024Article
272 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
The M2 protein of influenza A virus is a membrane-spanning tetrameric proton channel targeted by the antiviral drugs amantadine and rimantadine. Resistance to these drugs has compromised their effectiveness against many influenza strains, including pandemic H1N1. A recent crystal structure of M2(22-46) showed electron densities attributed to a single amantadine in the amino-terminal half of the pore, indicating a physical occlusion mechanism for inhibition. However, a solution NMR structure of M2(18-60) showed four rimantadines bound to the carboxy-terminal lipid-facing surface of the helices, suggesting an allosteric mechanism. Here we show by solid-state NMR spectroscopy that two amantadine-binding sites exist in M2 in phospholipid bilayers. The high-affinity site, occupied by a single amantadine, is located in the N-terminal channel lumen, surrounded by residues mutated in amantadine-resistant viruses. Quantification of the protein-amantadine distances resulted in a 0.3 A-resolution structure of the high-affinity binding site. The second, low-affinity, site was observed on the C-terminal protein surface, but only when the drug reaches high concentrations in the bilayer. The orientation and dynamics of the drug are distinct in the two sites, as shown by (2)H NMR. These results indicate that amantadine physically occludes the M2 channel, thus paving the way for developing new antiviral drugs against influenza viruses. The study demonstrates the ability of solid-state NMR to elucidate small-molecule interactions with membrane proteins and determine high-resolution structures of their complexes.
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.