ArticleAntimicrobial agents and chemotherapy2014
A conformational restriction in the influenza A virus neuraminidase binding site by R152 results in a combinational effect of I222T and H274Y on oseltamivir resistance.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Molecular dynamics study on the effect of the N1 neuraminidase double mutant G147R/H274Y on oseltamivir sensitivity.RSC advances · 2024Article
- Drug resistance and possible therapeutic options against influenza A virus infection over past years.Archives of microbiology · 2024Review
- Article
- Drug resistance in influenza A virus: the epidemiology and management.Infection and drug resistance · 2017Review
- The Path of Least Resistance: Mechanisms to Reduce Influenza's Sensitivity to Oseltamivir.Journal of molecular biology · 2016Article
- Influenza A(H7N9) virus acquires resistance-related neuraminidase I222T substitution when infected mallards are exposed to low levels of oseltamivir in water.Antimicrobial agents and chemotherapy · 2015Article
- Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates.Antimicrobial agents and chemotherapy · 2015Article
- Oseltamivir-resistant influenza A (H1N1) virus strain with an H274Y mutation in neuraminidase persists without drug pressure in infected mallards.Applied and environmental microbiology · 2015Article
- Understanding the cross-resistance of oseltamivir to H1N1 and H5N1 influenza A neuraminidase mutations using multidimensional computational analyses.Drug design, development and therapy · 2015Article
- Molecular surveillance of antiviral drug resistance of influenza A/H3N2 virus in Singapore, 2009-2013.PloS one · 2015Article
- Evolution of oseltamivir resistance mutations in Influenza A(H1N1) and A(H3N2) viruses during selection in experimentally infected mice.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The I222K, I222R, and I222T substitutions in neuraminidase (NA) have been found in clinically derived 2009 pandemic influenza A/H1N1 viruses with altered susceptibilities to NA inhibitors (NAIs). The effects of these substitutions, together with the most frequently observed resistance-related substitution, H274Y, on viral fitness and resistance mechanisms were further investigated in this study. Reduced sensitivities to oseltamivir were observed in all three mutants (I222K, I222R, and I222T). Furthermore, the I222K and I222T substitutions had a combinational effect of further increasing resistance in the presence of H274Y, which might result from a conformational restriction in the NA binding site. Of note, by using molecular dynamics simulations, R152, the neighbor of T222, was observed to translate to a position closer to T222, resulting in the narrowing of the binding pocket, which otherwise only subtends the residue substitution of H274Y. Moreover, significantly attenuated NA function and viral growth abilities were found in the I222K+H274Y double mutant, while the I222T+H274Y double mutant exhibited slightly delayed growth but had a peak viral titer similar to that of the wild-type virus in MDCK cells. The relative growth advantage of the I222T mutant versus the I222K mutant and the higher frequency of I222T emerging in N1 subtype influenza viruses raise concerns necessitating close monitoring of the dual substitutions I222T and H274Y.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.