Isocyanides as Influenza A Virus Subtype H5N1 Wild‐Type M2 Channel Inhibitors
Copyright policy )Isocyanides as Influenza A Virus Subtype H5N1 Wild‐Type M2 Channel Inhibitors
AbstractBasic bulky amines such as amantadine are well‐characterized M2 channel blockers, useful for treating influenza. Herein we report our surprising findings that charge‐neutral, bulky isocyanides exhibit activities similar to—or even higher than—that of amantadine. We also demonstrate that these isocyanides have potent growth inhibitory activity against the H5N1 virus. The −NH2 to −N≡C group replacement within current anti‐influenza drugs was found to give compounds with high activities at low‐micromolar concentrations. For example, a tenfold improvement in potency was observed for 1‐isocyanoadamantane (27), with an EC50 value of 0.487 μm against amantadine‐sensitive H5N1 virus as determined by both MTT and plaque‐reduction assays, without showing cytotoxicity. Furthermore, the isocyanide analogues synthesized in this study did not inhibit the V27A or S31N mutant M2 ion channels, according to electrophysiology experiments, and did not exhibit activity against amantadine‐resistant virus strains.
- National Research Council Italy
- Guangzhou Institutes of Biomedicine and Health China (People's Republic of)
- University of Milan Italy
- Wuhan University China (People's Republic of)
- Chinese Academy of Sciences China (People's Republic of)
antivirus agent, virus strain, 5 (tert butyl) 2 isocyano 1, isocyanide, synthesis, matrix protein, IC50, proton nuclear magnetic resonance, virus inhibition, Madin Darby Canine Kidney Cells, Viroporin Proteins, 6 trimethylbicyclo[3.1.1, n [4 (tert butyl)cyclohexyl]formamide, dose response, Influenza A Virus, animal, 3 isocyanoadamantan 1 ol, influenza A, 1 (1 isocyanoethyl)adamantine, development and aging, 6 trimethylbicyclo[3.1.1]heptan 3 yl)formamide, MDCK cell line, unclassified drug, n (adamantan 1 yl)formamide, EC50, microbial sensitivity test, Influenza A virus (H1N1), 2 isocyanoadamantane, priority journal, 1 isocyanoadamantane, Influenza A virus, Influenza A virus (H5N1), dog, antiviral activity, M2 channels; amantadines; antiviral agents; influenza; inhibitors; isocyanides, H5N1 Subtype, Drug, 6 trimethylbicyclo[3.1.1]heptane, 6, 4, growth, animal experiment, Microbial Sensitivity Tests, 4 trimethylpentane, chemistry, Antiviral Agents, Article, drug clearance, Dose-Response Relationship, Viral Matrix Proteins, Structure-Activity Relationship, 3 dimethylbenzene, Dogs, n ( 2, site directed mutagenesis, Animals, controlled study, drug binding site, M2 protein, mouse, antagonists and inhibitors, structure activity relation, amantadine, cyanide, nonhuman, Cyanides, Dose-Response Relationship, Drug, Influenza A Virus, H5N1 Subtype, microbiology, molecular docking, carbon nuclear magnetic resonance, molecular dynamics, 3 isocyano 2, drug effects, 1 (tert butyl) 4 isocyanocyclohexane, 2 isocyano 2, drug synthesis, Influenza virus, metabolism, virus attachment
antivirus agent, virus strain, 5 (tert butyl) 2 isocyano 1, isocyanide, synthesis, matrix protein, IC50, proton nuclear magnetic resonance, virus inhibition, Madin Darby Canine Kidney Cells, Viroporin Proteins, 6 trimethylbicyclo[3.1.1, n [4 (tert butyl)cyclohexyl]formamide, dose response, Influenza A Virus, animal, 3 isocyanoadamantan 1 ol, influenza A, 1 (1 isocyanoethyl)adamantine, development and aging, 6 trimethylbicyclo[3.1.1]heptan 3 yl)formamide, MDCK cell line, unclassified drug, n (adamantan 1 yl)formamide, EC50, microbial sensitivity test, Influenza A virus (H1N1), 2 isocyanoadamantane, priority journal, 1 isocyanoadamantane, Influenza A virus, Influenza A virus (H5N1), dog, antiviral activity, M2 channels; amantadines; antiviral agents; influenza; inhibitors; isocyanides, H5N1 Subtype, Drug, 6 trimethylbicyclo[3.1.1]heptane, 6, 4, growth, animal experiment, Microbial Sensitivity Tests, 4 trimethylpentane, chemistry, Antiviral Agents, Article, drug clearance, Dose-Response Relationship, Viral Matrix Proteins, Structure-Activity Relationship, 3 dimethylbenzene, Dogs, n ( 2, site directed mutagenesis, Animals, controlled study, drug binding site, M2 protein, mouse, antagonists and inhibitors, structure activity relation, amantadine, cyanide, nonhuman, Cyanides, Dose-Response Relationship, Drug, Influenza A Virus, H5N1 Subtype, microbiology, molecular docking, carbon nuclear magnetic resonance, molecular dynamics, 3 isocyano 2, drug effects, 1 (tert butyl) 4 isocyanocyclohexane, 2 isocyano 2, drug synthesis, Influenza virus, metabolism, virus attachment
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).20 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!