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Basic Characteristics of Mutations
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Mutation Site
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E212T |
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Mutation Site Sentence
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For example, a recent clinical study revealed that failure of DTG treatment in patients was observed with concomitant appearance of IN N155H/K211R/E212T substitutions on the background of the K156N polymorphic mutation . |
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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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IN |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
|
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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INSTs |
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Location
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- |
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Literature Information
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PMID
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31120420
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Title
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HIV-1 integrase tetramers are the antiviral target of pyridine-based allosteric integrase inhibitors
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Author
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Koneru PC,Francis AC,Deng N,Rebensburg SV,Hoyte AC,Lindenberger J,Adu-Ampratwum D,Larue RC,Wempe MF,Engelman AN,Lyumkis D,Fuchs JR,Levy RM,Melikyan GB,Kvaratskhelia M
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Journal
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eLife
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Journal Info
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2019 May 23;8:e46344
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Abstract
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Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a promising new class of antiretroviral agents that disrupt proper viral maturation by inducing hyper-multimerization of IN. Here we show that lead pyridine-based ALLINI KF116 exhibits striking selectivity for IN tetramers versus lower order protein oligomers. IN structural features that are essential for its functional tetramerization and HIV-1 replication are also critically important for KF116 mediated higher-order IN multimerization. Live cell imaging of single viral particles revealed that KF116 treatment during virion production compromises the tight association of IN with capsid cores during subsequent infection of target cells. We have synthesized the highly active (-)-KF116 enantiomer, which displayed EC(50) of ~7 nM against wild type HIV-1 and ~10 fold higher, sub-nM activity against a clinically relevant dolutegravir resistant mutant virus suggesting potential clinical benefits for complementing dolutegravir therapy with pyridine-based ALLINIs.
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Sequence Data
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-
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