Comparative proteomics reveals that YK51, a 4-Hydroxypandurantin-A analogue, downregulates the expression of proteins associated with dengue virus infection

Tan, Wei Lian and Lee, Yean Kee and Ho, Yen Fong and Yusof, Rohana and Abd Rahman, Noorsaadah and Karsani, Saiful Anuar (2018) Comparative proteomics reveals that YK51, a 4-Hydroxypandurantin-A analogue, downregulates the expression of proteins associated with dengue virus infection. PeerJ, 5. e3939. ISSN 2167-8359

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Official URL: https://doi.org/10.7717/peerj.3939

Abstract

Dengue is endemic throughout tropical and subtropical regions of the world. Currently, there is no clinically approved therapeutic drug available for this acute viral infection. Although the first dengue vaccine Dengvaxia has been approved for use in certain countries, it is limited to those without a previous dengue infection while the safety and efficacy of the vaccine in those elderly and younger children still need to be identified. Therefore, it is becoming increasingly important to develop therapeutics/drugs to combat dengue virus (DENV) infection. YK51 is a synthetic analogue of 4-Hydroxypandurantin A (a compound found in the crude extract of the rhizomes of Boesenbergia rotunda) that has been extensively studied by our research group. It has been shown to possess outstanding antiviral activity due to its inhibitory activity against NS2B/NS3 DENV2 protease. However, it is not known how YK51 affects the proteome of DENV infected cells. Therefore, we performed a comparative proteomics analysis to identify changes in protein expression in DENV infected HepG2 cells treated with YK51. Classical two-dimensional gel electrophoresis followed by protein identification using tandem mass spectrometry was employed in this study. Thirty proteins were found to be down-regulated with YK51 treatment. In silico analysis predicted that the down-regulation of eight of these proteins may inhibit viral infection. Our results suggested that apart from inhibiting the NS2B/NS3 DENV2 protease, YK51 may also be causing the down-regulation of a number of proteins that may be responsible in, and/or essential to virus infection. However, functional characterization of these proteins will be necessary before we can conclusively determine their roles in DENV infection.

Item Type: Article
Uncontrolled Keywords: Anti-viral compound; Dengue virus type-2; Inhibitory activity; Proteomics
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Q Science > QH Natural history
R Medicine
Divisions: Faculty of Medicine
Faculty of Science > Dept of Chemistry
Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 27 Feb 2019 02:27
Last Modified: 27 Feb 2019 02:27
URI: http://eprints.um.edu.my/id/eprint/20520

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