ArticleJournal of medicinal chemistry2014
Aminoadamantanes with persistent in vitro efficacy against H1N1 (2009) influenza A.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 73 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
- A bacteria-based search for drugs against avian and swine flu yields a potent and resistance-resilient channel blocker.Proceedings of the National Academy of Sciences of the United States of America · 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
- Applications of Bridgehead Heterocycles in Drug Design and Medicinal Chemistry.Topics in current chemistry (Cham) · 2025Review
- Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing.Acta pharmaceutica Sinica. B · 2024Review
- Synthesis and Testing of Analogs of the Tuberculosis Drug Candidate SQ109 against Bacteria and Protozoa: Identification of Lead Compounds againstACS infectious diseases · 2023Article
- Emulating Membrane Protein Environments─How Much Lipid Is Required for a Native Structure: Influenza S31N M2.Journal of the American Chemical Society · 2022Article
- Potential for the Repurposing of Adamantane Antivirals for COVID-19.Drugs in R&D · 2021Review
- Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.Biophysical journal · 2021Article
- Chemical Probes for Blocking of Influenza A M2 Wild-type and S31N Channels.ACS chemical biology · 2020Article
- Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment.International journal of antimicrobial agents · 2020Article
- Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses.Journal of medicinal chemistry · 2018Article
- Profiling the in vitro drug-resistance mechanism of influenza A viruses towards the AM2-S31N proton channel blockers.Antiviral research · 2018Article
- Unraveling the Binding, Proton Blockage, and Inhibition of Influenza M2 WT and S31N by Rimantadine Variants.ACS medicinal chemistry letters · 2018Article
- Novel antimitotic agents related to tubuloclustin: synthesis and biological evaluation.Molecular diversity · 2017Article
- Slow but Steady Wins the Race: Dissimilarities among New Dual Inhibitors of the Wild-Type and the V27A Mutant M2 Channels of Influenza A Virus.Journal of medicinal chemistry · 2017Article
- Binding and Proton Blockage by Amantadine Variants of the Influenza M2Journal of medicinal chemistry · 2017Article
- Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited.ACS medicinal chemistry letters · 2017Article
- Structure and Mechanism of the Influenza A M218-60 Dimer of Dimers.Journal of the American Chemical Society · 2015Article
- Influenza virus M2 protein ion channel activity helps to maintain pandemic 2009 H1N1 virus hemagglutinin fusion competence during transport to the cell surface.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
A series of 2-adamantanamines with alkyl adducts of various lengths were examined for efficacy against strains of influenza A including those having an S31N mutation in M2 proton channel that confer resistance to amantadine and rimantadine. The addition of as little as one CH2 group to the methyl adduct of the amantadine/rimantadine analogue, 2-methyl-2-aminoadamantane, led to activity in vitro against two M2 S31N viruses A/Calif/07/2009 (H1N1) and A/PR/8/34 (H1N1) but not to a third A/WS/33 (H1N1). Solid state NMR of the transmembrane domain (TMD) with a site mutation corresponding to S31N shows evidence of drug binding. But electrophysiology using the full length S31N M2 protein in HEK cells showed no blockade. A wild type strain, A/Hong Kong/1/68 (H3N2) developed resistance to representative drugs within one passage with mutations in M2 TMD, but A/Calif/07/2009 S31N was slow (>8 passages) to develop resistance in vitro, and the resistant virus had no mutations in M2 TMD. The results indicate that 2-alkyl-2-aminoadamantane derivatives with sufficient adducts can persistently block p2009 influenza A in vitro through an alternative mechanism. The observations of an HA1 mutation, N160D, near the sialic acid binding site in both 6-resistant A/Calif/07/2009(H1N1) and the broadly resistant A/WS/33(H1N1) and of an HA1 mutation, I325S, in the 6-resistant virus at a cell-culture stable site suggest that the drugs tested here may block infection by direct binding near these critical sites for virus entry to the host cell.
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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.