tetano
Editor, Senior Moderator
J Gen Virol. 2016 Mar 2. doi: 10.1099/jgv.0.000444. [Epub ahead of print]
[h=1]The significance of naturally occurring neuraminidase quasispecies of H5N1 avian influenza virus on resistance to oseltamivir: a point of concern.[/h] Schaduangrat N[SUP]1[/SUP], Phanich J[SUP]2[/SUP], Rungrotmongkol T[SUP]3[/SUP], Lerdsamran H[SUP]4[/SUP], Puthavathana P[SUP]5[/SUP], Ubol S[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Viral adaptability and survival arise due to the presence of quasispecies populations that are able to escape the immune response or produce drug-resistant variants. However, the presence of H5N1 virus with natural mutations acquired without any drug selection pressure, poses a great threat. Cloacal samples collected from the 2004-2005 epidemics in Thailand from Asian open-billed storks revealed one major and several minor quasispecies populations with mutations on the oseltamivir binding site of the neuraminidase gene (NA) without prior exposure to a drug. Therefore, this study investigated the binding between the NA containing novel mutations and oseltamivir drug (OTV) using molecular dynamic (MD) simulations and plaque inhibition assay. The results revealed that the mutant populations, S236F mutant, S236F/C278Y mutant, A250V/V266A/P271H/G285S mutant and C278Y mutant, had a lower binding affinity with OTV as compared to the wild-type virus due to rearrangement of amino acid residues and increased flexibility in the 150-loop. This result was further emphasized through the obtained IC50 values of the major population and wild-type virus, 104.74nM and 18.30nM respectively. Taken together, these data suggests that H5N1 viruses isolated from wild birds, have already acquired oseltamivir resistant point mutations without any exposure to a drug.
PMID: 26935590 [PubMed - as supplied by publisher]
[h=1]The significance of naturally occurring neuraminidase quasispecies of H5N1 avian influenza virus on resistance to oseltamivir: a point of concern.[/h] Schaduangrat N[SUP]1[/SUP], Phanich J[SUP]2[/SUP], Rungrotmongkol T[SUP]3[/SUP], Lerdsamran H[SUP]4[/SUP], Puthavathana P[SUP]5[/SUP], Ubol S[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Viral adaptability and survival arise due to the presence of quasispecies populations that are able to escape the immune response or produce drug-resistant variants. However, the presence of H5N1 virus with natural mutations acquired without any drug selection pressure, poses a great threat. Cloacal samples collected from the 2004-2005 epidemics in Thailand from Asian open-billed storks revealed one major and several minor quasispecies populations with mutations on the oseltamivir binding site of the neuraminidase gene (NA) without prior exposure to a drug. Therefore, this study investigated the binding between the NA containing novel mutations and oseltamivir drug (OTV) using molecular dynamic (MD) simulations and plaque inhibition assay. The results revealed that the mutant populations, S236F mutant, S236F/C278Y mutant, A250V/V266A/P271H/G285S mutant and C278Y mutant, had a lower binding affinity with OTV as compared to the wild-type virus due to rearrangement of amino acid residues and increased flexibility in the 150-loop. This result was further emphasized through the obtained IC50 values of the major population and wild-type virus, 104.74nM and 18.30nM respectively. Taken together, these data suggests that H5N1 viruses isolated from wild birds, have already acquired oseltamivir resistant point mutations without any exposure to a drug.
PMID: 26935590 [PubMed - as supplied by publisher]