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Basic Characteristics of Mutations
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Mutation Site
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D146A |
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Mutation Site Sentence
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The SPR assay indicated that theaflavin had a stronger binding activity with ZIKV NS5 wild-type (WT)-MTase than it with D146A-MTase. |
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Mutation Level
|
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
|
KU321639.1
|
|
Functional Impact and Mechanisms
|
|
Disease
|
-
|
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Immune
|
- |
|
Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
theaflavin |
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Location
|
- |
|
Literature Information
|
|
PMID
|
33898335
|
|
Title
|
Identification and Characterization of Zika Virus NS5 Methyltransferase Inhibitors
|
|
Author
|
Song W,Zhang H,Zhang Y,Chen Y,Lin Y,Han Y,Jiang J
|
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Journal
|
Frontiers in cellular and infection microbiology
|
|
Journal Info
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2021 Apr 7;11:665379
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Abstract
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The recurring outbreak of Zika virus (ZIKV) worldwide makes an emergent demand for novel, safe and efficacious anti-ZIKV agents. ZIKV non-structural protein 5 (NS5) methyltransferase (MTase), which is essential for viral replication, is regarded as a potential drug target. In our study, a luminescence-based methyltransferase assay was used to establish the ZIKV NS5 MTase inhibitor screening model. Through screening a natural product library, we found theaflavin, a polyphenol derived from tea, could inhibit ZIKV NS5 MTase activity with a 50% inhibitory concentration (IC(50)) of 10.10 muM. Molecular docking and site-directed mutagenesis analyses identified D146 as the key amino acid in the interaction between ZIKV NS5 MTase and theaflavin. The SPR assay indicated that theaflavin had a stronger binding activity with ZIKV NS5 wild-type (WT)-MTase than it with D146A-MTase. Moreover, theaflavin exhibited a dose dependent inhibitory effect on ZIKV replication with a 50% effective concentration (EC(50)) of 8.19 muM. All these results indicate that theaflavin is likely to be a promising lead compound against ZIKV.
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Sequence Data
|
-
|