ArticlePloS one2013
Inhibitors of the influenza A virus M2 proton channel discovered using a high-throughput yeast growth restoration assay.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 56 citations in OpenAlex.
- 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
- Article
- SARS-CoV-2 E protein: Pathogenesis and potential therapeutic development.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Fusion-inhibition peptide broadly inhibits influenza virus and SARS-CoV-2, including Delta and Omicron variants.Emerging microbes & infections · 2022Article
- Secondary Structure of Influenza A Virus Genomic Segment 8 RNA Folded in a Cellular Environment.International journal of molecular sciences · 2022Article
- Amantadine has potential for the treatment of COVID-19 because it inhibits known and novel ion channels encoded by SARS-CoV-2.Communications biology · 2021Article
- Potential for the Repurposing of Adamantane Antivirals for COVID-19.Drugs in R&D · 2021Review
- Hypothetical targets and plausible drugs of coronavirus infection caused by SARS-CoV-2.Transboundary and emerging diseases · 2021Review
- Outliers in SAR and QSAR: 3. Importance of considering the role of water molecules in protein-ligand interactions and quantitative structure-activity relationship studies.Journal of computer-aided molecular design · 2021Article
- Similarities between the effect of SARS-CoV-2 and HCV on the cellular level, and the possible role of ion channels in COVID19 progression: a review of potential targets for diagnosis and treatment.Channels (Austin, Tex.) · 2020Review
- Virtual Screening Identifies Chebulagic Acid as an Inhibitor of the M2(S31N) Viral Ion Channel and Influenza A Virus.Molecules (Basel, Switzerland) · 2020Article
- Put a cork in it: Plugging the M2 viral ion channel to sink influenza.Antiviral research · 2020Review
- Heterocyclic Inhibitors of Viroporins in the Design of Antiviral Compounds.Chemistry of heterocyclic compounds · 2020Article
- Alternative Experimental Models for Studying Influenza Proteins, Host-Virus Interactions and Anti-Influenza Drugs.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Studies of novel bioprobes isolated from rare natural sources using mutant yeasts.The Journal of antibiotics · 2019Review
- Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors.Frontiers in cellular and infection microbiology · 2019Article
- Design and synthesis of heteroaromatic-based benzenesulfonamide derivatives as potent inhibitors of H5N1 influenza A virus.MedChemComm · 2019Article
- Inhibitors of the M2 Proton Channel Engage and Disrupt Transmembrane Networks of Hydrogen-Bonded Waters.Journal of the American Chemical Society · 2018Article
- Yeast for virus research.Microbial cell (Graz, Austria) · 2017Review
- Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus.European journal of medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. Progress in developing new drugs has been hampered by the lack of a robust assay with sufficient throughput for discovery of new active chemotypes among chemical libraries and sufficient sensitivity to provide the SAR data essential for their improvement and development as drugs. In this study we adapted a yeast growth restoration assay, in which expression of the M2 channel inhibits yeast growth and exposure to an M2 channel inhibitor restores growth, into a robust and sensitive high-throughput screen for M2 channel inhibitors. A screen of over 250,000 pure chemicals and semi-purified fractions from natural extracts identified 21 active compounds comprising amantadine, rimantadine, 13 related adamantanes and 6 non-adamantanes. Of the non-adamantanes, hexamethylene amiloride and a triazine derivative represented new M2 inhibitory chemotypes that also showed antiviral activity in a plaque reduction assay. Of particular interest is the fact that the triazine derivative was not sufficiently potent for detection as an inhibitor in the traditional two electrode voltage clamp assay for M2 channel activity, but its discovery in the yeast assay led to testing of analogues of which one was as potent as amantadine.
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