Abstract: The MD simulations show that the V27A, V27F, G34E, and R45H mutations increase the diameter and hydration state of the pore in complex with compound 3.
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: This approach not only identified M2 mutations around the drug-binding site, including the pore-lining residues (V27A,
Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N/L26I and M2-S31N/V27A from the influenza A viruses.
PMID: 31669761
2020
European journal of pharmaceutical sciences
Abstract: In this study, we identified four amantadine-resistant M2 mutants among avian and human influenza A H5N1 strains circulating between 2002 and 2019: the single S31N and V27A mutants, and the S31N/L26I and S31N/V27A double mutants.
Abstract: Three compounds 6, 7, and 15 were found to significantly block all three M2 mutants: M2-S31N, M2-S31N/L26I, and M2-S31N/V27A.
Abstract: Using r
Discovery of M2 channel blockers targeting the drug-resistant double mutants M2-S31N/L26I and M2-S31N/V27A from the influenza A viruses.
Introduction: Here we present X-ray crystal structures of the drug-resistant V27A mutant of M2 bound to a spiro-adamantyl amine inhibitor, using both M2(22-46) and M2(21-61) constructs for crystallization trials.
Introduction: In the structure of M2(21-61) V27A bound to spiro-adamantyl amine, we observe tight packing at the channel's C-terminus, particularly at residue Arg45.
Introduction: In this study, we focus on understanding the mechanism of action of spiro-adamantyl amine in inhibiting the M2 V27A mutant by solving high-resolution X-ray crystal structures.
Introduction: It was found that when Val27 is mutated to Ala, the diameter of the channel pore at
Epidemic of influenza A(H1N1)pdm09 analyzed by full genome sequences and the first case of oseltamivir-resistant strain in Myanmar 2017.
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).
Genetic variability of avian influenza virus subtype H5N8 in Egypt in 2017 and 2018.
Abstract: Analysis of these viruses revealed mutations specific to Egyptian strains and not the original virus characterized in 2017 (A/duck/Egypt/F446/2017), with a novel antiviral resistance marker, V27A, indicating resistance to amantadine in the M2 protein of two strains.
Amantadine resistance markers among low pathogenic avian influenza H9N2 viruses isolated from poultry in India, during 2009-2017.
Abstract: Matrix genes of 48H9N2 viruses isolated from India during 2009-2017 were sequenced and M2 trans-membrane region sequences were screened for mutations which are known to confer resistance to amantadine namely, L26F, V27A, A30 T/V, S31N and G34E.
Abstract: Four isolates showed presence of V27A + S31 N dual mutations.
Genome-wide characterization of the seasonal H3N2 virus in Shanghai reveals natural temperature-sensitive strains conferred by the I668V mutation in the PA subunit.
Introduction: Amantadine resistance in transmissible viruses can be caused by conservative (V27A) or nonconservative (L26F and S31N) mutations in the AM2 channel.
Discussion: As such, only a limited number of AM2 mutants were identified in transmissible viruses such as V27A, L26F, and S31N.
A Robust Proton Flux (pHlux) Assay for Studying the Function and Inhibition of the Influenza A M2 Proton Channel.
Abstract: The inhibition of M2 was measured for five different inhibitors, including Rimantadine, Amantadine, and spiro type compounds, and the drug resistance of the M2 mutant variants (swine flu, V27A, and S31N) was confirmed.
IV mutation literature information.
PMID: 
2020
ACS pharmacology & translational science
Browser Board
Co-occurred Entities
Filtrator
ViMRT