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Basic Characteristics of Mutations
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Mutation Site
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N294S |
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Mutation Site Sentence
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We examined two resistant NA mutations, H274Y and N294S, and one non-drug-resistant mutation, E119G. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NA |
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Standardized Encoding Gene
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NA
|
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Genotype/Subtype
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H5N1 |
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Viral Reference
|
-
|
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Functional Impact and Mechanisms
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Disease
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Influenza A
|
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Immune
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- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
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Clinical Information
|
- |
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Treatment
|
oseltamivir |
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Location
|
Vietnam |
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Literature Information
|
|
PMID
|
19309695
|
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Title
|
Computational studies of H5N1 influenza virus resistance to oseltamivir
|
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Author
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Wang NX,Zheng JJ
|
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Journal
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Protein science : a publication of the Protein Society
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Journal Info
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2009 Apr;18(4):707-15
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Abstract
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Influenza A (H5N1) virus is one of the world's greatest pandemic threats. Neuraminidase (NA) inhibitors, oseltamivir and zanamivir, prevent the spread of influenza, but drug-resistant viruses have reduced their effectiveness. Resistance depends on the binding properties of NA-drug complexes. Key residue mutations within the active site of NA glycoproteins diminish binding, thereby resulting in drug resistance. We performed molecular simulations and calculations to characterize the mechanisms of H5N1 influenza virus resistance to oseltamivir and predict potential drug-resistant mutations. We examined two resistant NA mutations, H274Y and N294S, and one non-drug-resistant mutation, E119G. Six-nanosecond unrestrained molecular dynamic simulations with explicit solvent were performed using NA-oseltamivir complexes containing either NA wild-type H5N1 virus or a variant. MM_PBSA techniques were then used to rank the binding free energies of these complexes. Detailed analyses indicated that conformational change of E276 in the Pocket 1 region of NA is a key source of drug resistance in the H274Y mutant but not in the N294S mutant.
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Sequence Data
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-
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