Genetic diversity of influenza A viruses circulating in Bulgaria during the 2018-2019 winter season.
PMID: 32459617
2020
Journal of medical microbiology
Result: As with the vast majority of A(H1N1)pdm09 viruses, M2 proteins carried S31N substitution associated with resistance to M2-ion channel blockers (amantadine and rimantadine).
Genetic and antigenic characterization of influenza A/H5N1 viruses isolated from patients in Indonesia, 2008-2015.
Result: Various amantadine resistance substitutions in the M2 protein were also found in all 35 isolates, including V27A (34 viruses), V27T (1 virus), S31G (1 virus), and S31N (5 viruses).
Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.
Abstract: In the active M2 S31N blockers 1 and 6, the phenyl and isoxazolyl head groups achieve a deeper binding position and high kon/low koff and high kon/high koff rate constants, compared to inactive 2-5, which have much lower kon and higher koff.
Abstract: Infection of cell cultures by influenza virus containing M2 WT or M2 S31N is inhibited by 1-5 or 1-4 and 6, respectively.
Abstract: Study of 1-6 shows that, according to molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations, all bind in the M2 S31N channel with the adamantyl group positioned between V27 and G34 and the aryl group projecting out of the channel with the phenyl (or isoxazole in 6) embedded in the V
Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.
Result: After 20 hours' incubation, expression of M2(S31N) reduced yeast growth to 30.6 +- 11.6% (mean +- SD) of the strain treated with glucose, while expression of M2(S31) reduced growth to 24.4 +- 12.9% of glucose-treated cells.
Result: Although not assessed by TEVC or plaque reduction assay, a thiophene derivative (compound 6) was selected as it restores growth of bacteria expressing M2(S31N), which would otherwise inhibit bacterial growth, with an EC50 of 25 microM.
Result: As expected, amantadine effectively inhibited PR8M2(S31) replication (EC50 = 0.16 +- 0.02 microM; mean +- s.e.m.) but not PR8M2(S31N) (EC50 > 5 microM), while M2WSJ352 selectively inhibited PR8M2(S31N) (EC50 = 3.2 +- 1.2 microM) over PR8M2(S31) (EC50 = 32.7 +- 16.1 mic
Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.
Abstract: Overall, this is the first systematic study of the drug resistance mechanism of M2-S31N channel blockers using multiple viruses in different cell lines.
Abstract: Recent efforts in drug development against influenza A virus (IAV) M2 proton channel S31N mutant resulted in conjugates of amantadine linked with aryl head heterocycles.
Abstract: The Molecular Mechanics Generalized Born (MM-GBSA) calculations result in more positive binding free energies for the complexes of resistant M2 (V27A, V27F, G34E, R45H) with compound 3 compared to the stable complexes (S31N and I32N).
Abstract: To und
Functional neuraminidase inhibitor resistance motifs in avian influenza A(H5Nx) viruses.
Discussion: Today a high proportion of the circulating avian influenza viruses possess mutations such as L26I or S31N, which confer resistance to amantadine.
Characterization of neuraminidase inhibitor-resistant influenza virus isolates from immunocompromised patients in the Republic of Korea.
Introduction: However, since most recently detected type A influenza viruses harbor the resistance variation S31N in the matrix gene, the M2 proton-channel blockers amantadine and rimantadine are no longer clinically applied.
Design and synthesis of pinane oxime derivatives as novel anti-influenza agents.
Abstract: Currently, to design non-adamantane compounds targeting the S31N mutant of M2 proton channel is a promising direction for the development of novel anti-influenza drugs.
Abstract: In our previous research, a pinanamine-based antiviral M090 was discovered to target hemagglutinin instead of M2, with its structure being highly similar to reported M2-S31N inhibitors.
Abstract: Utilizing a combination of structure-activity relationship analysis, electrophysiological assay and molecular docking, the most potent compound 11h, as a M2-S31N blocker, exhibited excellent activity with EC50 value at the low micromolar level against both H3N2 and H1N1.
Differential Viral-Host Immune Interactions Associated with Oseltamivir-Resistant H275Y and Wild-Type H1N1 A(pdm09) Influenza Virus Pathogenicity.
Introduction: The pdm09 matrix protein (MP) gene came from the Eurasian swine lineage, which contains the S31N mutation conferring resistance to adamantine antiviral therapeutics.
Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.
Abstract: In this study, serial viral passages were applied to select resistance against a newly developed isoxazole-conjugated adamantane inhibitor that targets the AM2 S31N channel.
Abstract: It was found that the L46P mutation caused a conformational change in the N terminus of transmembrane residues 22-31 that ultimately broadened the drug-binding site of AM2 S31N inhibitor 4, which spans residues 26-34, but not of AM2 WT inhibitor amantadine, which spans residues 31-34.
Abstract: Molecular dynamics simulations showed that L46P causes a dilation of drug-binding site between residues 22 and 31, which affects the binding of AM2 S31N channel blockers, but not the AM2 WT inhibitor amantadine.
Abstract: Overall, these results demonstrate a unique allosteric resistance mechanism toward AM2
IV mutation literature information.
PMID: 
2020
Journal of medical microbiology
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