Introduction: Compounds 1-4 have low micromolar or submicromolar potency, similar to amantadine or rimantadine, inhibiting the amantadine-sensitive A/WSN/33 M2 N31S (M2 WT) replication at concentations 0.09 - 1.13 muM (WT, Table 1), while 5 has a mediocre antiviral activity (8.10 muM).
Introduction: EC50 values for the A/WSN/33 (M2 N31) and A/WSN/33 M2 N31S constructs represented in Table 1 can be compared and contrasted with Kd values in the last columns of Tables 2 and 3, respectively.
Introduction: We applied the cytopathic effect (CPE) inhibition assay to compare the antiviral activity of 1-6 against the A/WSN/33 virus (with naturally occurring M2 N31) and the A/WSN/33 M2
Investigation of the Drug Resistance Mechanism of M2-S31N Channel Blockers through Biomolecular Simulations and Viral Passage Experiments.
Abstract: This approach not only identified M2 mutations around the drug-binding site, including the pore-lining residues (V27A, V27F, N31S, and G34E) and an interhelical residue (I32N), but also a new allosteric mutation (R45H), in addition to L46P previously identified, located at the C-terminus of M2 that is more than 10 A away from the drug-binding site.
Early season co-circulation of influenza A(H3N2) and B(Yamagata): interim estimates of 2017/18 vaccine effectiveness, Canada, January 2018.
Method: The delNS1 virus harboring an amantadine sensitive mutation, N31S, in M2 protein (M2-
Result: In agreement with previous reports, LC3 puncta were hardly colocalized with GFP-LAMP2, a lysosomal marker, in amantadine sensitive M2-N31S delNS1-infected cells (Figure 1G).
Result: In contrast, by adding 50 muM amantadine, a potent inhibitor of M2 ion channel activity, LAMP2 was colocalized with autophagosomes in M2-N31S delNS1-infected cells (Figures 1G,H).
Figure: (G,H) HeLa cells expressing GFP-LAMP2 (shown in magenta) were infected with M2-N31S delNS1 virus at MOI of 3 with or without 50 muM amantadine (Amt).
An M2-V27A channel blocker demonstrates potent in vitro and in vivo antiviral activities against amantadine-sensitive and -resistant influenza A viruses.
Result: Further increasing the concentration of amantadine (1) to 50 muM also failed to significantly inhibit the replication of the A/WSN/33 (M2-N31S + V27A) (H1N1) virus (plaque reduction less than 10 %).
Result: We then tested the antiviral activity of compounds 7 and 16 against both M2-WT-containing A/Udorn/72 (M2-WT) (H3N2) virus and the M2-V27A-containing A/WSN/33 (
Result: When tested against another M2-WT-containing virus A/WSN/33 (M2-N31S) (H1N1) virus, both amantadine (1) and compound 3 showed potent antiviral activity with EC50 values of 0.2 +- 0.01 muM, and 0.1 +- 0.01 muM, respectively (Table S1).
Slow but Steady Wins the Race: Dissimilarities among New Dual Inhibitors of the Wild-Type and the V27A Mutant M2 Channels of Influenza A Virus.
PMID: 28418242
2017
Journal of medicinal chemistry
Method: The PRA with A/WSN/33 N31S/V27A (H1N1) virus was carried out similarly as previously described.
Result: The anti-influenza virus activity of compounds 2, 3, 7 and 19, that inhibited the V27A channel (Table 1), was also determined in MDCK cells using a 46-h virus PRA with the A/WSN/33 virus (H1N1 subtype), which carries a N31S/V27A M2 protein.
Genomic signature and protein sequence analysis of a novel influenza A (H7N9) virus that causes an outbreak in humans in China.
Abstract: N31S-M2WSN was amantadine sensitive, whereas A/WSN/33 was amantadine resistant, indicating that the M2 residue N31 is the sole determinant of resistance of A/WSN/33 to amantadine.
Abstract: We have investigated the effect of amantadine on the growth of four influenza viruses: A/WSN/33; N31S-M2WSN, a mutant in which an asparagine residue at position 31 in the M2 TM domain was replaced with a serine residue; MUd/WSN, which possesses seven RNA segments from WSN plus the RNA segment 7 derived from A/Udorn/72; and A/Udorn/72.
IV mutation literature information.
PMID: 
2020
ACS chemical biology
Browser Board
Co-occurred Entities
Filtrator
ViMRT