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Basic Characteristics of Mutations
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Mutation Site
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D535A |
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Mutation Site Sentence
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Importantly, the surface plasmon resonance assay showed that UA had strong direct binding with ZIKV wild-type RdRp and a relatively weak interaction with D535A-RdRp. |
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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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NS5 |
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Standardized Encoding Gene
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NS5
|
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Genotype/Subtype
|
- |
|
Viral Reference
|
-
|
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Functional Impact and Mechanisms
|
|
Disease
|
-
|
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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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- |
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Treatment
|
10-undecenoic acid zinc salt (UA) |
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Location
|
- |
|
Literature Information
|
|
PMID
|
31310806
|
|
Title
|
Identification and characterization of Zika virus NS5 RNA-dependent RNA polymerase inhibitors
|
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Author
|
Lin Y,Zhang H,Song W,Si S,Han Y,Jiang J
|
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Journal
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International journal of antimicrobial agents
|
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Journal Info
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2019 Oct;54(4):502-506
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Abstract
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The current outbreak of Zika virus (ZIKV) is the impetus for novel, safe and efficacious anti-ZIKV agents. ZIKV non-structural protein 5 RNA-dependent RNA polymerase (RdRp) is essential for viral replication and is logically regarded as an attractive drug target. This study used a fluorescence-based polymerase assay to find an anti-infective drug 10-undecenoic acid zinc salt (UA) which could inhibit RdRp activity with a half maximal inhibitory concentration (IC(50)) of 1.13-1.25 microM. Molecular docking and site-directed mutagenesis analyses identified D535 as the key amino acid in the interaction between RdRp and UA. Importantly, the surface plasmon resonance assay showed that UA had strong direct binding with ZIKV wild-type RdRp and a relatively weak interaction with D535A-RdRp. As a control, the nucleoside inhibitor sofosbuvir triphosphate (PSI-7409) conferred insensitivity to the fluorescence-based RdRp assay and cannot bind directly with RdRp. Moreover, UA showed anti-ZIKV activity comparable to sofosbuvir. All these results indicate that UA is likely to be a promising lead compound against ZIKV, exhibiting a different mechanism than sofosbuvir.
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Sequence Data
|
-
|