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https://ptsldigital.ukm.my/jspui/handle/123456789/499797Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Nazlina Ibrahim, Prof Madya Dr. | |
| dc.contributor.author | Norefrina Shafinaz Md. Nor (P54872) | |
| dc.date.accessioned | 2023-10-13T09:34:49Z | - |
| dc.date.available | 2023-10-13T09:34:49Z | - |
| dc.date.issued | 2015-11-08 | |
| dc.identifier.other | ukmvital:83421 | |
| dc.identifier.uri | https://ptsldigital.ukm.my/jspui/handle/123456789/499797 | - |
| dc.description | A study was conducted to investigate the antiviral effect of a styrylpyrone derivative (SPD) from the root of Goniothalamus umbrosus and its possible antiviral mechanism(s) against Herpes Simplex Virus type 1. Nucleotide magnetic resonance, Gas chromatography, and Fourier Transform Infra Red done and confirmed that the compound was an SPD known as Goniothalamin. The antiviral activity has been confirmed by conducting plaque reduction assay which involved post-treatment, pre-treatment and virucidal tests. SPD activity was determined to reduce HSV-1 plaque by more than 80% when given as post-treatment at 12.5 μM. SPD treatment was found to affect the yield of HSV-1 progeny. In time addition assay, where SPD was given at different time intervals (2, 4, 6, 8, 10) hours post-infection (hpi), SPD anti-HSV-1 activity was found to be most optimum when given at 2 hpi (>80% plaque reduction). In time removal assay where SPD treatment was given at 2 hpi and removed at different time intervals (3, 6, 9, 12, 15, 18 hpi) showed that >80% plaque reduction was achieved when treatment of SPD was given until 15 hpi. Investigation of SPD possible anti-HSV-1 mechanism was done utilising Next Generation Sequencing (NGS) for transcriptome analysis. Data of overexpressed genes from HSV-1 infected sample that have been treated with SPD (SPD-HSV-1) was grouped into functional clusters that showed the most enriched cluster was found to associate with regulation of apoptosis and regulation of cell cycle (10 hpi). Investigation on the pathway correlated to this group of genes utilising the Kyoto Encyclopaedia of Genes (KEGG) revealed that the p53 dependent pathway was the main pathway being activated and regulated in SPD-HSV-1. Two sub-pathways (cell cycle involving p21 pathway and intrinsic apoptosis) from p53 dependent pathway was validated by Real Time quantitative polymerase chain reaction (RT-qPCR). p21waf1/cip1 (p21), puma (bbc3), bax, bcl-xl and apaf-1 (intrinsic apoptosis pathway) p21, ccnd1, ccne1 cdk2 and e2f1 (p21 cell cycle arrest pathway) were validated. Results showed that apoptosis signal have been triggered early in SPD-HSV-1 with puma and apaf-1 peaked earlier at 8 hpi, subsequent peaked of bax/bcl-xl ratio with down regulation of p21 at 10 hpi. Cell cycle genes ccnd1 and ccne1 and cell proliferation marker e2f1 expression was down regulated following overexpression of p21. Observation of cell through immunocytochemistry detected Vero cell with apoptosis characteristic of membrane blebbing and chromosome condensation at ~14 hpi only in SPD-HSV-1 sample. Investigation on HSV-1 IE ICP0 at 10 hpi showed marked increased of expression (>14 fold) while ICP4 gene expression was found to be down regulated ~18 fold when compared to expression in HSV-1 control infection. Investigation of HSV-1 late genes associated with ICP4 gB, gH and gC showed down regulation in gene expression for all genes. Based on analysis done in this study, SPD anti-HSV-1 activity was observed to have association with apoptosis and cell cycle arrest early during HSV-1 infection in SPD-HSV-1 cell, which caused limited host cell cycle accessory that can be used in viral replication. The non-permissive environment for HSV-1 replication had caused reduction in HSV-1 progeny in accordance with the down regulation of IE gene and late gene of HSV-1.,Ph.D | |
| dc.language.iso | eng | |
| dc.publisher | UKM, Bangi | |
| dc.relation | Faculty of Science and Technology / Fakulti Sains dan Teknologi | |
| dc.rights | UKM | |
| dc.subject | Goniothalamus umbrosus | |
| dc.title | Antiviral mechanism of a styrylpyrone derivative (spd) from goniothalamus umbrosus against herpes simplex virus type 1 (hsv-1) | |
| dc.type | Theses | |
| dc.format.pages | 2,227 | |
| dc.identifier.barcode | 001861 | |
| Appears in Collections: | Faculty of Science and Technology / Fakulti Sains dan Teknologi | |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| ukmvital_83421+SOURCE1+SOURCE1.0.PDF Restricted Access | 33.99 MB | Adobe PDF |  View/Open |
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