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Identification of a small-molecule inhibitor of dengue virus using a replicon system
Dengue virus (DENV) is a mosquito-borne human pathogen that causes a serious public-health threat in tropical and subtropical regions of the world. Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harbor...
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Published in: | Archives of virology 2012-04, Vol.157 (4), p.681-688 |
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creator | Hsu, Yu-Chen Chen, Nai-Chi Chen, Po-Chiang Wang, Chun-Chung Cheng, Wei-Chieh Wu, Huey-Nan |
description | Dengue virus (DENV) is a mosquito-borne human pathogen that causes a serious public-health threat in tropical and subtropical regions of the world. Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW |
doi_str_mv | 10.1007/s00705-012-1224-z |
format | article |
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Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW < 500 Da) chemicals were evaluated for their ability to reduce luciferase reporter activity in cell lysates. One effective compound was identified from the screening. This compound was found to reduce virus production but did not block virus entry in virus-based assay. Mode-of-action analysis revealed that this inhibitor suppressed viral RNA replication but did not affect replicon translation. This compound potentially could be developed as an anti-DENV agent and might be useful for dissecting the molecular mechanism of DENV replication.</description><identifier>ISSN: 0304-8608</identifier><identifier>EISSN: 1432-8798</identifier><identifier>DOI: 10.1007/s00705-012-1224-z</identifier><identifier>PMID: 22249364</identifier><language>eng</language><publisher>Vienna: Springer Vienna</publisher><subject>Animals ; Antiviral Agents - chemistry ; Antiviral Agents - isolation & purification ; Antiviral Agents - pharmacology ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cell Line ; Dengue fever ; Dengue virus ; Dengue Virus - drug effects ; Drug Evaluation, Preclinical - methods ; Fundamental and applied biological sciences. Psychology ; Genes, Reporter ; Humans ; Infectious Diseases ; Luciferases - genetics ; Luciferases - metabolism ; Medical Microbiology ; Microbiology ; Miscellaneous ; Molecular biology ; Molecular Structure ; Original Article ; Pathogens ; Plasmids ; Proteins ; Replicon - drug effects ; Staining and Labeling ; Vaccines ; Virology ; Virus Internalization - drug effects ; Virus Replication - drug effects ; Viruses</subject><ispartof>Archives of virology, 2012-04, Vol.157 (4), p.681-688</ispartof><rights>Springer-Verlag 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-f3e042b2262071f2f0c9f6eb0d31920251d5ed3a52766d7e36c7ebd5716871b23</citedby><cites>FETCH-LOGICAL-c499t-f3e042b2262071f2f0c9f6eb0d31920251d5ed3a52766d7e36c7ebd5716871b23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25755300$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22249364$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsu, Yu-Chen</creatorcontrib><creatorcontrib>Chen, Nai-Chi</creatorcontrib><creatorcontrib>Chen, Po-Chiang</creatorcontrib><creatorcontrib>Wang, Chun-Chung</creatorcontrib><creatorcontrib>Cheng, Wei-Chieh</creatorcontrib><creatorcontrib>Wu, Huey-Nan</creatorcontrib><title>Identification of a small-molecule inhibitor of dengue virus using a replicon system</title><title>Archives of virology</title><addtitle>Arch Virol</addtitle><addtitle>Arch Virol</addtitle><description>Dengue virus (DENV) is a mosquito-borne human pathogen that causes a serious public-health threat in tropical and subtropical regions of the world. Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW < 500 Da) chemicals were evaluated for their ability to reduce luciferase reporter activity in cell lysates. One effective compound was identified from the screening. This compound was found to reduce virus production but did not block virus entry in virus-based assay. Mode-of-action analysis revealed that this inhibitor suppressed viral RNA replication but did not affect replicon translation. This compound potentially could be developed as an anti-DENV agent and might be useful for dissecting the molecular mechanism of DENV replication.</description><subject>Animals</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - isolation & purification</subject><subject>Antiviral Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Line</subject><subject>Dengue fever</subject><subject>Dengue virus</subject><subject>Dengue Virus - drug effects</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes, Reporter</subject><subject>Humans</subject><subject>Infectious Diseases</subject><subject>Luciferases - genetics</subject><subject>Luciferases - metabolism</subject><subject>Medical Microbiology</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Molecular biology</subject><subject>Molecular Structure</subject><subject>Original Article</subject><subject>Pathogens</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Replicon - drug effects</subject><subject>Staining and Labeling</subject><subject>Vaccines</subject><subject>Virology</subject><subject>Virus Internalization - drug effects</subject><subject>Virus Replication - drug effects</subject><subject>Viruses</subject><issn>0304-8608</issn><issn>1432-8798</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp9kV1rFTEQhoNY7LH6A7yRRRC9iU6-N5dS_CgUelOvl2x2ckzJ7h6T3UL7683hHC0I7c0EMs_7TiYvIW8YfGIA5nOpBRQFxinjXNL7Z2TDpOC0NbZ9TjYgQNJWQ3tKXpZyA1AvhHpBTnmlrdByQ64vBpyWGKJ3S5ynZg6Na8roUqLjnNCvCZs4_Yp9XOa871Z8u2JzG_NamrXEaVsFGXcp-iovd2XB8RU5CS4VfH08z8jPb1-vz3_Qy6vvF-dfLqmX1i40CATJe841B8MCD-Bt0NjDIJjlwBUbFA7CKW60HgwK7Q32gzJMt4b1XJyRDwffXZ5_r1iWbozFY0puwnktndVCWoAWKvnxSbJ-Z9sK1hpZ0Xf_oTfzmqe6R2eVkNzWWiF2gHyeS8kYul2Oo8t31WlvZrpDNl3Npttn091Xzduj8dqPOPxT_A2jAu-PgCvepZDd5GN54JRRSsB-GX7gSm1NW8wPL3x8-h9_2aVm</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Hsu, Yu-Chen</creator><creator>Chen, Nai-Chi</creator><creator>Chen, Po-Chiang</creator><creator>Wang, Chun-Chung</creator><creator>Cheng, Wei-Chieh</creator><creator>Wu, Huey-Nan</creator><general>Springer Vienna</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>7X8</scope></search><sort><creationdate>20120401</creationdate><title>Identification of a small-molecule inhibitor of dengue virus using a replicon system</title><author>Hsu, Yu-Chen ; Chen, Nai-Chi ; Chen, Po-Chiang ; Wang, Chun-Chung ; Cheng, Wei-Chieh ; Wu, Huey-Nan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-f3e042b2262071f2f0c9f6eb0d31920251d5ed3a52766d7e36c7ebd5716871b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - isolation & purification</topic><topic>Antiviral Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Line</topic><topic>Dengue fever</topic><topic>Dengue virus</topic><topic>Dengue Virus - drug effects</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Fundamental and applied biological sciences. 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Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW < 500 Da) chemicals were evaluated for their ability to reduce luciferase reporter activity in cell lysates. One effective compound was identified from the screening. This compound was found to reduce virus production but did not block virus entry in virus-based assay. Mode-of-action analysis revealed that this inhibitor suppressed viral RNA replication but did not affect replicon translation. This compound potentially could be developed as an anti-DENV agent and might be useful for dissecting the molecular mechanism of DENV replication.</abstract><cop>Vienna</cop><pub>Springer Vienna</pub><pmid>22249364</pmid><doi>10.1007/s00705-012-1224-z</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Antiviral Agents - chemistry Antiviral Agents - isolation & purification Antiviral Agents - pharmacology Biological and medical sciences Biomedical and Life Sciences Biomedicine Cell Line Dengue fever Dengue virus Dengue Virus - drug effects Drug Evaluation, Preclinical - methods Fundamental and applied biological sciences. Psychology Genes, Reporter Humans Infectious Diseases Luciferases - genetics Luciferases - metabolism Medical Microbiology Microbiology Miscellaneous Molecular biology Molecular Structure Original Article Pathogens Plasmids Proteins Replicon - drug effects Staining and Labeling Vaccines Virology Virus Internalization - drug effects Virus Replication - drug effects Viruses |
title | Identification of a small-molecule inhibitor of dengue virus using a replicon system |
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