Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin
In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the “heat clearing” class of herbs. We show that luteolin inhibits the replicatio...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2017
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| Online Access: | https://hdl.handle.net/10356/86618 http://hdl.handle.net/10220/44137 |
| _version_ | 1811697530681950208 |
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| author | Peng, Minhua Watanabe, Satoru Chan, Kitti Wing Ki He, Qiuyan Zhao, Ya Zhang, Zhongde Lai, Xiaoping Luo, Dahai Vasudevan, Subhash G. Li, Geng |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Peng, Minhua Watanabe, Satoru Chan, Kitti Wing Ki He, Qiuyan Zhao, Ya Zhang, Zhongde Lai, Xiaoping Luo, Dahai Vasudevan, Subhash G. Li, Geng |
| author_sort | Peng, Minhua |
| collection | NTU |
| description | In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the “heat clearing” class of herbs. We show that luteolin inhibits the replication of all four serotypes of dengue virus, but the selectivity of the inhibition was weak. In addition, ADE-mediated dengue virus infection of human cell lines and primary PBMCs was inhibited. In a time-of-drug-addition study, luteolin was found to reduce infectious virus particle formation, but not viral RNA synthesis, in Huh-7 cells. During the virus life cycle, the host protease furin cleaves the pr moiety from prM protein of immature virus particles in the trans-Golgi network to produce mature virions. Analysis of virus particles from luteolin-treated cells revealed that prM was not cleaved efficiently. Biochemical interrogation of human furin showed that luteolin inhibited the enzyme activity in an uncompetitive manner, with Ki value of 58.6 μM, suggesting that treatment may restrict the virion maturation process. Luteolin also exhibited in vivo antiviral activity in mice infected with DENV, causing reduced viremia. Given the mode of action of luteolin and its widespread source, it is possible that it can be tested in combination with other dengue virus inhibitors. |
| first_indexed | 2024-10-01T07:56:44Z |
| format | Journal Article |
| id | ntu-10356/86618 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:56:44Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/866182020-11-01T05:29:55Z Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin Peng, Minhua Watanabe, Satoru Chan, Kitti Wing Ki He, Qiuyan Zhao, Ya Zhang, Zhongde Lai, Xiaoping Luo, Dahai Vasudevan, Subhash G. Li, Geng Lee Kong Chian School of Medicine (LKCMedicine) Luteolin Dengue Virus In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the “heat clearing” class of herbs. We show that luteolin inhibits the replication of all four serotypes of dengue virus, but the selectivity of the inhibition was weak. In addition, ADE-mediated dengue virus infection of human cell lines and primary PBMCs was inhibited. In a time-of-drug-addition study, luteolin was found to reduce infectious virus particle formation, but not viral RNA synthesis, in Huh-7 cells. During the virus life cycle, the host protease furin cleaves the pr moiety from prM protein of immature virus particles in the trans-Golgi network to produce mature virions. Analysis of virus particles from luteolin-treated cells revealed that prM was not cleaved efficiently. Biochemical interrogation of human furin showed that luteolin inhibited the enzyme activity in an uncompetitive manner, with Ki value of 58.6 μM, suggesting that treatment may restrict the virion maturation process. Luteolin also exhibited in vivo antiviral activity in mice infected with DENV, causing reduced viremia. Given the mode of action of luteolin and its widespread source, it is possible that it can be tested in combination with other dengue virus inhibitors. NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Accepted version 2017-12-13T06:44:32Z 2019-12-06T16:25:53Z 2017-12-13T06:44:32Z 2019-12-06T16:25:53Z 2017 Journal Article Peng, M., Watanabe, S., Chan, K. W. K., He, Q., Zhao, Y., Zhang, Z., et al. (2017). Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin. Antiviral Research, 143, 176-185. 0166-3542 https://hdl.handle.net/10356/86618 http://hdl.handle.net/10220/44137 10.1016/j.antiviral.2017.03.026 en Antiviral Research © 2017 Elsevier B.V. This is the author created version of a work that has been peer reviewed and accepted for publication by Antiviral Research, Elsevier B.V. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.antiviral.2017.03.026]. 48 p. application/pdf |
| spellingShingle | Luteolin Dengue Virus Peng, Minhua Watanabe, Satoru Chan, Kitti Wing Ki He, Qiuyan Zhao, Ya Zhang, Zhongde Lai, Xiaoping Luo, Dahai Vasudevan, Subhash G. Li, Geng Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin |
| title | Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin |
| title_full | Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin |
| title_fullStr | Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin |
| title_full_unstemmed | Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin |
| title_short | Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin |
| title_sort | luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin |
| topic | Luteolin Dengue Virus |
| url | https://hdl.handle.net/10356/86618 http://hdl.handle.net/10220/44137 |
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