{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:44:25Z","timestamp":1790660665094,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2014,7,17]],"date-time":"2014-07-17T00:00:00Z","timestamp":1405555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hand, foot and mouth disease (HFMD) is a common pediatric illness mainly caused by infection with enterovirus 71 (EV71) and coxsackievirus A16 (CA16). The frequent HFMD outbreaks have become a serious public health problem. Currently, no vaccine or antiviral drug for EV71\/CA16 infections has been approved. In this study, a two-step screening platform consisting of reporter virus-based assays and cell viability\u2011based assays was developed to identify potential inhibitors of EV71\/CA16 infection. Two types of reporter viruses, a pseudovirus containing luciferase-encoding RNA replicons encapsidated by viral capsid proteins and a full-length reporter virus containing enhanced green fluorescent protein, were used for primary screening of 400 highly purified natural compounds. Thereafter, a cell viability-based secondary screen was performed for the identified hits to confirm their antiviral activities. Three compounds (luteolin, galangin, and quercetin) were identified, among which luteolin exhibited the most potent inhibition of viral infection. In the cell viability assay and plaque reduction assay, luteolin showed similar 50% effective concentration (EC50) values of about 10 \u03bcM. Luteolin targeted the post-attachment stage of EV71 and CA16 infection by inhibiting viral RNA replication. This study suggests that luteolin may serve as a lead compound to develop potent anti-EV71 and CA16 drugs.<\/jats:p>","DOI":"10.3390\/v6072778","type":"journal-article","created":{"date-parts":[[2014,7,17]],"date-time":"2014-07-17T11:26:30Z","timestamp":1405596390000},"page":"2778-2795","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell  Viability-Based Screening"],"prefix":"10.3390","volume":"6","author":[{"given":"Lin","family":"Xu","sequence":"first","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiheng","family":"Su","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyan","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"College of Basic Medical Sciences, Dalian Medical University, Dalian 116000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyang","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peihu","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"An","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Kong","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonghui","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Dalian Medical University, Dalian 116000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlai","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jilin University, Changchun 130012, China"},{"name":"National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China"},{"name":"Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/S1474-4422(08)70207-2","article-title":"Enterovirus 71 infection: A new threat to global public health?","volume":"7","author":"Qiu","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/j.1348-0421.2002.tb02743.x","article-title":"Outbreak of central nervous 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