Loading…

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...

Full description

Saved in:
Bibliographic Details
Published in:Archives of virology 2012-04, Vol.157 (4), p.681-688
Main Authors: Hsu, Yu-Chen, Chen, Nai-Chi, Chen, Po-Chiang, Wang, Chun-Chung, Cheng, Wei-Chieh, Wu, Huey-Nan
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c499t-f3e042b2262071f2f0c9f6eb0d31920251d5ed3a52766d7e36c7ebd5716871b23
cites cdi_FETCH-LOGICAL-c499t-f3e042b2262071f2f0c9f6eb0d31920251d5ed3a52766d7e36c7ebd5716871b23
container_end_page 688
container_issue 4
container_start_page 681
container_title Archives of virology
container_volume 157
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
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_963490080</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2620592731</sourcerecordid><originalsourceid>FETCH-LOGICAL-c499t-f3e042b2262071f2f0c9f6eb0d31920251d5ed3a52766d7e36c7ebd5716871b23</originalsourceid><addsrcrecordid>eNp9kV1rFTEQhoNY7LH6A7yRRRC9iU6-N5dS_CgUelOvl2x2ckzJ7h6T3UL7683hHC0I7c0EMs_7TiYvIW8YfGIA5nOpBRQFxinjXNL7Z2TDpOC0NbZ9TjYgQNJWQ3tKXpZyA1AvhHpBTnmlrdByQ64vBpyWGKJ3S5ynZg6Na8roUqLjnNCvCZs4_Yp9XOa871Z8u2JzG_NamrXEaVsFGXcp-iovd2XB8RU5CS4VfH08z8jPb1-vz3_Qy6vvF-dfLqmX1i40CATJe841B8MCD-Bt0NjDIJjlwBUbFA7CKW60HgwK7Q32gzJMt4b1XJyRDwffXZ5_r1iWbozFY0puwnktndVCWoAWKvnxSbJ-Z9sK1hpZ0Xf_oTfzmqe6R2eVkNzWWiF2gHyeS8kYul2Oo8t31WlvZrpDNl3Npttn091Xzduj8dqPOPxT_A2jAu-PgCvepZDd5GN54JRRSsB-GX7gSm1NW8wPL3x8-h9_2aVm</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>953429953</pqid></control><display><type>article</type><title>Identification of a small-molecule inhibitor of dengue virus using a replicon system</title><source>Springer Link</source><creator>Hsu, Yu-Chen ; Chen, Nai-Chi ; Chen, Po-Chiang ; Wang, Chun-Chung ; Cheng, Wei-Chieh ; Wu, Huey-Nan</creator><creatorcontrib>Hsu, Yu-Chen ; Chen, Nai-Chi ; Chen, Po-Chiang ; Wang, Chun-Chung ; Cheng, Wei-Chieh ; Wu, Huey-Nan</creatorcontrib><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 &lt; 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 &amp; 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&amp;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 &lt; 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 &amp; 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 &amp; 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. Psychology</topic><topic>Genes, Reporter</topic><topic>Humans</topic><topic>Infectious Diseases</topic><topic>Luciferases - genetics</topic><topic>Luciferases - metabolism</topic><topic>Medical Microbiology</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Molecular biology</topic><topic>Molecular Structure</topic><topic>Original Article</topic><topic>Pathogens</topic><topic>Plasmids</topic><topic>Proteins</topic><topic>Replicon - drug effects</topic><topic>Staining and Labeling</topic><topic>Vaccines</topic><topic>Virology</topic><topic>Virus Internalization - drug effects</topic><topic>Virus Replication - drug effects</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><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><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) 1: Biological Sciences &amp; Living Resources</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) 3: Aquatic Pollution &amp; Environmental Quality</collection><collection>Aquatic Science &amp; Fisheries Abstracts (ASFA) Professional</collection><collection>MEDLINE - Academic</collection><jtitle>Archives of virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsu, Yu-Chen</au><au>Chen, Nai-Chi</au><au>Chen, Po-Chiang</au><au>Wang, Chun-Chung</au><au>Cheng, Wei-Chieh</au><au>Wu, Huey-Nan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of a small-molecule inhibitor of dengue virus using a replicon system</atitle><jtitle>Archives of virology</jtitle><stitle>Arch Virol</stitle><addtitle>Arch Virol</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>157</volume><issue>4</issue><spage>681</spage><epage>688</epage><pages>681-688</pages><issn>0304-8608</issn><eissn>1432-8798</eissn><abstract>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 &lt; 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>
fulltext fulltext
identifier ISSN: 0304-8608
ispartof Archives of virology, 2012-04, Vol.157 (4), p.681-688
issn 0304-8608
1432-8798
language eng
recordid cdi_proquest_miscellaneous_963490080
source Springer Link
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
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T03%3A07%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Identification%20of%20a%20small-molecule%20inhibitor%20of%20dengue%20virus%20using%20a%20replicon%20system&rft.jtitle=Archives%20of%20virology&rft.au=Hsu,%20Yu-Chen&rft.date=2012-04-01&rft.volume=157&rft.issue=4&rft.spage=681&rft.epage=688&rft.pages=681-688&rft.issn=0304-8608&rft.eissn=1432-8798&rft_id=info:doi/10.1007/s00705-012-1224-z&rft_dat=%3Cproquest_cross%3E2620592731%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c499t-f3e042b2262071f2f0c9f6eb0d31920251d5ed3a52766d7e36c7ebd5716871b23%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=953429953&rft_id=info:pmid/22249364&rfr_iscdi=true