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Basic Characteristics of Mutations
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Mutation Site
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V740A |
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Mutation Site Sentence
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Subsequent sequencing of nonstructural genes of P15 viruses revealed two mutations, G641D and V740A, in the MT-like domain at the C terminus of nsP2. |
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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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nsP2 |
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Standardized Encoding Gene
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nsP2
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Genotype/Subtype
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- |
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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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Chikungunya Fever
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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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- |
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Location
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- |
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Literature Information
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PMID
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33903104
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Title
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Radicicol Inhibits Chikungunya Virus Replication by Targeting Nonstructural Protein 2
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Author
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Nam S,Ga YJ,Lee JY,Hwang WY,Jung E,Shin JS,Chen W,Choi G,Zhou B,Yeh JY,Go YY
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Journal
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Antimicrobial agents and chemotherapy
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Journal Info
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2021 Jun 17;65(7):e0013521
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Abstract
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Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a debilitating febrile illness characterized by persistent muscle and joint pain. The widespread distribution of transmission-competent vectors, Aedes species mosquitoes, indicates the potential risk of large-scale epidemics with high attack rates that can severely impact public health globally. Despite this, currently, there are no antivirals available for the treatment of CHIKV infections. Thus, we aimed to identify potential drug candidates by screening a chemical library using a cytopathic effect-based high-throughput screening assay. As a result, we identified radicicol, a heat shock protein 90 (Hsp90) inhibitor that effectively suppressed CHIKV replication by blocking the synthesis of both positive- and negative-strand viral RNA as well as expression of viral proteins. Interestingly, selection for viral drug-resistant variants and mutational studies revealed nonstructural protein 2 (nsP2) as a putative molecular target of radicicol. Moreover, coimmunoprecipitation and in silico modeling analyses determined that G641D mutation in the methyltransferase (MT)-like domain of nsP2 is essential for its interaction with cytoplasmic Hsp90beta chaperone. Our findings collectively support the potential application of radicicol as an anti-CHIKV agent. The detailed study of the underlying mechanism of action further contributes to our understanding of virus-host interactions for novel therapeutics against CHIKV infection.
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Sequence Data
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-
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