literature

IV mutation literature information.

The molecular characteristics of avian influenza viruses (H9N2) derived from air samples in live poultry markets.

PMID: 29331671 2018 Infection, genetics and evolution

Abstract: The N30D and T215A mutations in the M1 gene and amino acid residues L89V in PB2, P42S in NS1 and S31N in M2 were retained in these 9 strains of H9N2 isolates, which could enhance the virus's virulence.

Molecular genetic characteristics of influenza A virus clinically isolated during 2011-2016 influenza seasons in Korea.

PMID: 29489060 2018 Influenza and other respiratory viruses

Abstract: In addition, sequence analysis confirmed the several substitutions of internal genes and gene substitutions associated with drug resistance (I222V in NA and S31N in M2) in the fatal cases.

Discussion: Among these two substitutions, V51I may enhance the fitness of M2 protein to increase the frequency of adamantine resistance associated with S31N mutation and the substitution of V51-affected viral replication.28 The I39 of M2 was located in the transmembrane region, and substitution of the transmembrane region could affect M2 function, aiding in resistance to M2 inhibitors and transport to the cell surface.

Discussion: Previous

Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.

PMID: 29518414 2018 Antiviral research

Result: AM2-

Result: AM2-S31N inhibitors 1 and 2 have potent channel blockage and antiviral activity.

Result: After drug withdrawal at 1P10 for three additional passages, the 1P13 viral population retained the AM2-S31N/V27I mutation.

Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.

PMID: 29541360 2018 ACS medicinal chemistry letters

Abstract: Here, we investigate these concepts to explain binding and proton blockage of rimantadine variants bearing progressively larger alkyl groups to influenza A virus M2 wild type (WT) and M2 S31N protein proton channel.

Abstract: This is due to the fact that, in M2 S31N, the loss of the V27 pocket for the adamantyl cage resulted in low residence time inside the M2 pore.

Abstract: We showed that resistance of M2 S31N to rimantadine analogues compared to M2 WT resulted from their higher koff rates compared to the kon rates according to electrophysiology (EP) measurements.

Symmetric dimeric adamantanes for exploring the structure of two viroporins: influenza virus M2 and hepatitis C virus p7.

PMID: 29750015 2018 Drug design, development and therapy

Abstract: The lack of channel blockage of the dimeric amantadine and rimantadine analogs against M2 wild type and M2-S31N mutant was consistent with previously proposed drug-binding mechanisms and further confirmed that the pore-binding model is the pharmacologically relevant drug-binding model.

Result: A previous solution NMR structure of the inhibitor-bound M2-S31N structure showed that the inhibitor binds to the S31N mutant in a flipped orientation relative to that in the M2-WT channel.

Result: In our dimeric compounds, this polar aryl group is missing, which explains their lack of efficacy in inhibiting the M2-S31N channel.

Development of a quadruple qRT-PCR assay for simultaneous identification of highly and low pathogenic H7N9 avian influenza viruses and characterization against oseltamivir resistance.

PMID: 30111290 2018 BMC infectious diseases

Introduction: Neuraminidase inhibitors (NAIs) have been used as front-line therapeutic options since the novel H7N9 viruses contain the S31N mutation in the M2 protein, which confers resistance to the M2 ion channel blockers such as amantadine.

A 627K variant in the PB2 protein of H9 subtype influenza virus in wild birds.

PMID: 29999583 2018 Influenza and other respiratory viruses

Result: No amino acid substitutions were found in the M2 transmembrane domain, suggesting that this virus strain is sensitive to M2 ion channel inhibitors.23 The S31N amino acid substitution in the M2 protein was not present, indicating that these viral strains were sensitive to amantadine inhibitors.24 The virulence of influenza viruses in humans is related to their resistance to the antiviral effects of cytokines, such as interferon (IFN), and the D92E mutation in the NS1 protein increases resistance to IFN.25 However, no mutations at residue 92 of NS1 were observed in this study.

Mechanism and Kinetics of Copper Complexes Binding to the Influenza A M2 S31N and S31N/G34E Channels.

PMID: 30429954 2018 ACS medicinal chemistry letters

Abstract: Majority of current circulating influenza A viruses carry the S31N mutation in their M2 genes, rendering AM2-S31N as a high profile antiviral drug target.

Abstract: We also showed for the first time that AM2-S31N channel blockers such as 10e inhibited influenza virus replication at both low and high multiply of infection (102-106 pfu/mL) and the inhibition was not cell-type dependent.

Abstract: With our continuous interest in developing AM2-S31N channel blockers as novel antivirals targeting both oseltamivir-sensitive and -resistant influenza A viruses, we report herein the structure-property relationship studies of AM2-S31N inhibitors.

Genome-wide characterization of the seasonal H3N2 virus in Shanghai reveals natural temperature-sensitive strains conferred by the I668V mutation in the PA subunit.

PMID: 30353004 2018 Emerging microbes & infections