Viral M2 ion channel protein: a promising target for anti-influenza drug discovery.
PMID: 25342196
2014
Mini reviews in medicinal chemistry
Abstract: The biologically important compounds discovered using the scaffolds such as bisnoradmantane, noradamantane, triazine, spiroadamantane, isoxazole, amino alcohol, azaspiro, spirene, pinanamine, etc are reported to exhibit anti-influenza activity against wild or mutant type (S31N and V27A) of M2 proton channel protein.
Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.
PMID: 25470189
2014
Journal of the American Chemical Society
Abstract: For example, the wild-type (WT) influenza A viruses, such as the seasonal H1N1, tend to be sensitive to antiviral drugs, amantadine and rimantadine, while the S31N mutant viruses, such as the pandemic 2009 H1N1 (H1N1pdm09) and seasonal H3N2, are resistant to this class of drugs.
Abstract: Solution NMR studies and molecular dynamics (MD) simulations of drug-M2 interactions supported our design hypothesis: namely, the dual inhibitor binds in the WT M2 channel with an aromatic group facing down toward the C-terminus, while the same drug binds in the S31N M2 channel with its aromatic group facing up toward the N-terminus.
Abstract: The potency of the most active compound 11 in inhibiting WT and the S31N mutant influenza viruses is comparable with that of amantadine i
Discovery of Potential, Non-Toxic Influenza Virus Inhibitor by Computational Techniques.
Abstract: However, S31N mutation in M2 proton channel diminishes the efficiency of rimantadine and creates resistance.
Molecular and phylogenetic analysis of matrix gene of avian influenza viruses isolated from wild birds and live bird markets in the USA.
PMID: 22958470
2013
Influenza and other respiratory viruses
Abstract: Of these 17 isola
Introduction: 23 The most commonly observed mutation is at position 31 leading to change from serine to asparagine (S31N).
Result: Of these 17 isolates, 16 had S31N change and one isolate had V27A mutation (Table 2).
Discussion: High prevalence of S31N substitution in this study is in line with those observed earlier, as this substitution is considered to be the most common mutation conferring resistance to adamentanes 20 , whereas V27A mutation is rare in frequency (1 6%).
Discussion: Substitution at position 31 (S31N) in M2 protein was the most commonly observed substitution with 16 of the 17 isolate having this mutation, whereas only one isolate had V27A change.
High prevalence of amantadine-resistant influenza A virus isolated in Gyeonggi Province, South Korea, during 2005-2010.
Abstract: Among the handful of drug-resistant mutants, S31N is found in more than 95% of the currently circulating viruses and shows greatly decreased inhibition by amantadine.
Abstract: Nevertheless, we have discovered small-molecule drugs that inhibit S31N with potencies greater than amantadine's potency against WT M2.
Abstract: The discovery of inhibitors of S31N has been hampered by the limited size, polarity, and dynamic nature of its amantadine-binding site.
Abstract: This S31N inhibitor, like other potent M2 inhibitors, contains a charged ammonium group.
Inhibitors of the influenza A virus M2 proton channel discovered using a high-throughput yeast growth restoration assay.
Abstract: 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.
Introduction: These are single amino acid substitutions in the channel - V27A, L26F or S31N.
Result: Amantadine did not increase the growth of the S31N and V27A strains (Figs 1C, 1D), as expected since these mutated channels are amantadine-resistant.
Result: cerevisiae strains were generated containing a multicopy plasmid for expression of the wild-type, S31N-mutated, or V27A-mutated M2 gene from the Udorn strain of
Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.
PMID: 23437766
2013
Journal of medicinal chemistry
Abstract: S31N is the predominant and amantadine-resistant Abstract: However, the S31N mutant presents a huge challenge to drug discovery, and it has been considered undruggable for several decades.
Conclusion: On the basis of this work, several more potent series of S31N inhibitors have been discovered, one series has already been published, and others will be the subject of future reports.
Conclusion: Using a combination of structural information of M2 proton channel and medicinal chemistry approaches, we report the discovery of promising dual M2 inhibitors for S31N and WT M2 channels, demonstrating that M2 S31N is a druggable target.
Simultaneous detection of oseltamivir- and amantadine-resistant influenza by oligonucleotide microarray visualization.
Abstract: Consequently, a cost-effective oligonucleotide microarray visualization method, which was based on quantum dot-catalyzed silver deposition, was developed and evaluated for the simu
Introduction: Furthermore, more than 99% of amantadine resistance generally resulted from mutations V27A and S31N in M2.
Introduction: The objective of this study was to design a cost-effective oligonucleotide microarray visualization method to simultaneously detect NA H275Y, NA E119V, M2 V27A, and M2 S31N mutations of influenza A (H3N2), seasonal influenza A (H1N1), and 2009 influenza A (H1N1).
[Analysis of evolution features of whole genome of influenza virus H3N2 in Qingdao between year 2007 and 2011].
PMID: 23601520
2013
Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]
Abstract: The sequence analysis of M2 protein showed that the isolated influenza virus H3N2 mutated in amino acid site 31, from serine to asparagine (S31N).
IV mutation literature information.
PMID: 
2014
Mini reviews in medicinal chemistry
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