ArticleEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences2020
Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N/L26I and M2-S31N/V27A from the influenza A viruses.
Article in European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Antiviral Resistance in Influenza: Clinical and Public Health Implications.Influenza and other respiratory viruses · 2026Review
- Epidemiological and Genomic Characterization of H5 Subtype Avian Influenza Viruses in Jining City, 2024-2025.Pathogens (Basel, Switzerland) · 2026Article
- Adamantane-based inhibitors of the influenza A M2 proton channel: structure-based design, biological evaluation, and synthetic approaches.RSC medicinal chemistry · 2026Review
- Computational Structural Analysis Predicts Host-Range Promiscuity and Antiviral Resistance in North American H5N1 Lineages.Computational and structural biotechnology journal · 2026Article
- 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
- PA and PA-X: two key proteins from segment 3 of the influenza viruses.Frontiers in cellular and infection microbiology · 2025Review
- Compounds based on Adamantyl-substituted Amino Acids and Peptides as Potential Antiviral Drugs Acting as Viroporin Inhibitors.Current pharmaceutical design · 2024Review
- Antiviral Approaches against Influenza Virus.Clinical microbiology reviews · 2023Review
- Review
- MicroRNA-205-5p: A potential therapeutic target for influenza A.Journal of cellular and molecular medicine · 2022Article
- Influenza A virus polymerase acidic protein E23G/K substitutions weaken key baloxavir drug-binding contacts with minimal impact on replication and transmission.PLoS pathogens · 2022Article
- Photothermal card reader assay using the commercial colloidal gold test strip for the rapid quantitative detection of food hazards.Mikrochimica acta · 2022Article
- Rational design of a deuterium-containing M2-S31N channel blocker UAWJ280 withEmerging microbes & infections · 2021Article
- A chronicle of SARS-CoV-2: Seasonality, environmental fate, transport, inactivation, and antiviral drug resistance.Journal of hazardous materials · 2021Review
- Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.Biophysical journal · 2021Article
- Analysis of the Genetic Diversity Associated With the Drug Resistance and Pathogenicity of Influenza A Virus Isolated in Bangladesh From 2002 to 2019.Frontiers in microbiology · 2021Review
- Anti-Influenza Drug Discovery and Development: Targeting the Virus and Its Host by All Possible Means.Advances in experimental medicine and biology · 2021Article
- Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics.Journal of the American Chemical Society · 2020Article
- Highlighting membrane protein structure and function: A celebration of the Protein Data Bank.The Journal of biological chemistryReview
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Influenza virus infections are a persistent threat to human health due to seasonal outbreaks and sporadic pandemics. Amantadine and rimantadine are FDA-approved influenza antiviral drugs and work by inhibiting the viral M2 proton channel. However, the therapeutic potential for the antiviral amantadine/rimantadine was curtailed by the emergence of drug-resistant mutations in its target protein M2. In this study, we identified four amantadine-resistant M2 mutants among avian and human influenza A H5N1 strains circulating between 2002 and 2019: the single S31N and V27A mutants, and the S31N/L26I and S31N/V27A double mutants. Herein, utilizing two-electrode voltage clamp (TEVC) assays, we screened a panel of structurally diverse M2 inhibitors against these single and double mutant channels. Three compounds 6, 7, and 15 were found to significantly block all three M2 mutants: M2-S31N, M2-S31N/L26I, and M2-S31N/V27A. Using recombinant viruses generated from reverse genetics, we further showed that these compounds also inhibited the replication of recombinant viruses harboring either the single S31N or double S31N/L26I and S31N/V27A mutants. This work represents the first example in developing antivirals by targeting the drug-resistant double mutants of M2 proton channels.
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