Comparative proteomics reveals that YK51, a 4-Hydroxypandurantin-A analogue, downregulates the expression of proteins associated with dengue virus infection
| Autor: | Noorsaadah Abdul Rahman, Wei-Lian Tan, Yean Kee Lee, Saiful Anuar Karsani, Rohana Yusof, Yen Fong Ho |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Dengue virus type-2 Proteomics medicine.medical_treatment viruses lcsh:Medicine Biology Dengue virus medicine.disease_cause General Biochemistry Genetics and Molecular Biology Virus Dengue fever 03 medical and health sciences Evidence Based Medicine medicine Molecular Biology Dengue vaccine NS3 Protease 030102 biochemistry & molecular biology General Neuroscience lcsh:R Inhibitory activity General Medicine medicine.disease Virology 030104 developmental biology Infectious Diseases Proteome General Agricultural and Biological Sciences Anti-viral compound |
| Zdroj: | PeerJ PeerJ, Vol 5, p e3939 (2018) |
| ISSN: | 2167-8359 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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