Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based Screening
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 ap...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2014-07-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1999-4915/6/7/2778 |
| _version_ | 1818617225025683456 |
|---|---|
| author | Lin Xu Weiheng Su Jun Jin Jiawen Chen Xiaojun Li Xuyuan Zhang Meiyan Sun Shiyang Sun Peihu Fan Dong An Huafei Zhang Xiguang Zhang Wei Kong Tonghui Ma Chunlai Jiang |
| author_facet | Lin Xu Weiheng Su Jun Jin Jiawen Chen Xiaojun Li Xuyuan Zhang Meiyan Sun Shiyang Sun Peihu Fan Dong An Huafei Zhang Xiguang Zhang Wei Kong Tonghui Ma Chunlai Jiang |
| author_sort | Lin Xu |
| collection | DOAJ |
| description | 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‑based 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 μM. 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. |
| first_indexed | 2024-12-16T17:02:18Z |
| format | Article |
| id | doaj.art-c2f1c0c0fb214b1da40cc3c6d10b54cb |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-16T17:02:18Z |
| publishDate | 2014-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-c2f1c0c0fb214b1da40cc3c6d10b54cb2022-12-21T22:23:41ZengMDPI AGViruses1999-49152014-07-01672778279510.3390/v6072778v6072778Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based ScreeningLin Xu0Weiheng Su1Jun Jin2Jiawen Chen3Xiaojun Li4Xuyuan Zhang5Meiyan Sun6Shiyang Sun7Peihu Fan8Dong An9Huafei Zhang10Xiguang Zhang11Wei Kong12Tonghui Ma13Chunlai Jiang14School of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaCollege of Basic Medical Sciences, Dalian Medical University, Dalian 116000, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaHand, 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‑based 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 μM. 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.http://www.mdpi.com/1999-4915/6/7/2778enterovirus 71coxsackievirus A16luteolinreporter virushigh‑throughput assayantiviral drug discovery |
| spellingShingle | Lin Xu Weiheng Su Jun Jin Jiawen Chen Xiaojun Li Xuyuan Zhang Meiyan Sun Shiyang Sun Peihu Fan Dong An Huafei Zhang Xiguang Zhang Wei Kong Tonghui Ma Chunlai Jiang Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based Screening Viruses enterovirus 71 coxsackievirus A16 luteolin reporter virus high‑throughput assay antiviral drug discovery |
| title | Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based Screening |
| title_full | Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based Screening |
| title_fullStr | Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based Screening |
| title_full_unstemmed | Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based Screening |
| title_short | Identification of Luteolin as Enterovirus 71 and Coxsackievirus A16 Inhibitors through Reporter Viruses and Cell Viability-Based Screening |
| title_sort | identification of luteolin as enterovirus 71 and coxsackievirus a16 inhibitors through reporter viruses and cell viability based screening |
| topic | enterovirus 71 coxsackievirus A16 luteolin reporter virus high‑throughput assay antiviral drug discovery |
| url | http://www.mdpi.com/1999-4915/6/7/2778 |
| work_keys_str_mv | AT linxu identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT weihengsu identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT junjin identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT jiawenchen identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT xiaojunli identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT xuyuanzhang identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT meiyansun identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT shiyangsun identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT peihufan identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT dongan identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT huafeizhang identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT xiguangzhang identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT weikong identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT tonghuima identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening AT chunlaijiang identificationofluteolinasenterovirus71andcoxsackievirusa16inhibitorsthroughreportervirusesandcellviabilitybasedscreening |