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Title: Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin
Authors: Peng, Minhua
Watanabe, Satoru
Chan, Kitti Wing Ki
He, Qiuyan
Zhao, Ya
Zhang, Zhongde
Lai, Xiaoping
Luo, Dahai
Vasudevan, Subhash G.
Li, Geng
Keywords: Luteolin
Dengue Virus
Issue Date: 2017
Source: 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.
Series/Report no.: Antiviral Research
Abstract: 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.
ISSN: 0166-3542
DOI: 10.1016/j.antiviral.2017.03.026
Rights: © 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: [].
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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