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.
Flipping in the pore: discovery of dual inhibitors that bind in different orientations to the wild-type versus the amantadine-resistant S31N mutant of the influenza A virus M2 proton channel.
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: Ama
Figure: Yeast strains containing an empty plasmid (A) or plasmid bearing WT M2 (B), S31N M2 (C) or V27A M2 (D) were distributed into 96-well plates and their growth was measured over time following transfer at 0h to medium containing galactose and addition of the indicated concentrations of amantadine.
Discovery of novel dual inhibitors of the wild-type and the most prevalent drug-resistant mutant, S31N, of the M2 proton channel from influenza A virus.
PMID: 23437766
2013
Journal of medicinal chemistry
Introduction: 2-Chloro analogue 49 also showed much lower S31N activity than 44, which may be attributed to the fact that chlorine is a weaker hydrogen acceptor than a hydroxyl group.
Introduction: A secondary amine is preferred over an imine analogue for S31N activity (42% and 21% inhibition for compounds 20 and 26, respectively).
Introduction: Again, a variety of substituents were tolerated when the target was WT, but only the simple primary amine found in amantadine gave significant activity against S31N.
Introduction: Although the unsubstituted derivative 5 was inactive toward S31N (1% inhibition), it did show significant inhibition against the WT (77% inhibition) at 100 muM drug concentration.
Introduction: Amantadine (1) is, however, more active than rimantadine (2) against S31N (199.9 muM v
Simultaneous detection of oseltamivir- and amantadine-resistant influenza by oligonucleotide microarray visualization.
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).
Method: Moreover, microarray probes ranging from 17 to 21 nucleotides were designed to detect H275Y, E119V, 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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