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The extent of QC intercalation into RNA depends on the complexity of its secondary and tertiary structure. Internal ribosome entry sites (IRESs) that are required for initiation of translation of some viral and cellular mRNAs typically have complex structures. Recent work has shown that some intercalating drugs, including QC, are capable of inhibiting hepatitis C virus IRES-mediated translation in a cell-free system. Here, we show that QC suppresses translation directed by the encephalomyocarditis virus (EMCV) and poliovirus IRESs in a cell-free system and in virus-infected HeLa cells. In contrast, IRESs present in the mammalian p53 transcript that are predicted to have less-complex structures were not sensitive to QC. Inhibition of IRES-mediated translation by QC correlated with the affinity of binding between QC and the particular IRES. Expression of viral capsid proteins, replication of viral RNAs, and production of virus were all strongly inhibited by QC (and 9AA). These results suggest that QC and similar intercalating drugs could potentially be used for treatment of viral infections.<\/jats:p>","DOI":"10.1128\/jvi.02569-09","type":"journal-article","created":{"date-parts":[[2010,7,15]],"date-time":"2010-07-15T02:47:24Z","timestamp":1279162044000},"page":"9390-9397","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Inhibition of Encephalomyocarditis Virus and Poliovirus Replication by Quinacrine: Implications for the Design and Discovery of Novel Antiviral Drugs"],"prefix":"10.1128","volume":"84","author":[{"given":"Alexander V.","family":"Gasparian","sequence":"first","affiliation":[{"name":"Cleveland Biolabs, Inc., Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nickolay","family":"Neznanov","sequence":"additional","affiliation":[{"name":"Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujata","family":"Jha","sequence":"additional","affiliation":[{"name":"Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleksandr","family":"Galkin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Moran","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Cleveland State University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei V.","family":"Gudkov","sequence":"additional","affiliation":[{"name":"Cleveland Biolabs, Inc., Buffalo, New York"},{"name":"Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina V.","family":"Gurova","sequence":"additional","affiliation":[{"name":"Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton A.","family":"Komar","sequence":"additional","affiliation":[{"name":"Center for Gene Regulation in Health and Disease, Department of Biological, Geological and Environmental Sciences, Cleveland State University, Cleveland, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.12.5350"},{"key":"e_1_3_2_3_2","unstructured":"mMessage mMachine T7 Ultra kit technical manual. 2008"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja035117c"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.157806"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2009.07.005"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612053507459"},{"key":"e_1_3_2_8_2","first-page":"192","volume":"4","year":"2003","unstructured":"Blankenship, J. 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