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Basic Characteristics of Mutations
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Mutation Site
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Y188L |
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Mutation Site Sentence
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Among these, K103N, Y181C or Y188L, carried by RT, are the most prevalent mutants. |
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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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RT |
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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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HIV Infections
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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
|
NNRTIs;N-alkoxy indolylacetamide |
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Location
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- |
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Literature Information
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PMID
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32004936
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Title
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Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root
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Author
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Xu C,Xin Y,Chen M,Ba M,Guo Q,Zhu C,Guo Y,Shi J
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Journal
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European journal of medicinal chemistry
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Journal Info
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2020 Mar 1;189:112071
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Abstract
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From an aqueous decoction of the traditional Chinese medicine ""ban lan gen"" (the Isatis indigotica root), an antiviral natural product CI - 39 was isolated as an NNRTI (non-nucleoside reverse transcriptase inhibitor) (EC(50) = 3.40 muM). Its novel structure was determined as methyl (1-methoxy-1H-indol-3-yl)acetamidobenzoate by spectroscopic data and confirmed by single crystal X-ray diffraction. Through synthesis and structure-activity relationship (SAR) investigation of CI - 39 and 57 new derivatives (24 with EC(50) values of 0.06-8.55 muM), two optimized derivatives 10f and 10i (EC(50): 0.06 muM and 0.06 muM) having activity comparable to that of NVP (EC(50) = 0.03 muM) were obtained. Further evaluation verified that 10f and 10i were RT DNA polymerase inhibitors and exhibited better activities and drug resistance folds compared to NVP against seven NNRTI-resistant strains carrying different mutations. Especially, 10i (EC(50) = 0.43 muM) was more active to the L100I/K103N double-mutant strain as compared to both NVP (EC(50) = 0.76 muM) and EFV (EC(50) = 1.08 muM). The molecular docking demonstrated a possible binding pattern between 10i and RT and revealed activity mechanism of 10i against the NNRTI-resistant strains.
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Sequence Data
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-
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