dc.contributor.advisor |
Brimble, Margaret |
|
dc.contributor.author |
Ji, Junghun |
|
dc.date.accessioned |
2021-11-24T19:44:14Z |
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dc.date.available |
2021-11-24T19:44:14Z |
|
dc.date.issued |
2021 |
en |
dc.identifier.uri |
https://hdl.handle.net/2292/57542 |
|
dc.description |
Full Text is available to authenticated members of The University of Auckland only. |
en |
dc.description.abstract |
Norovirus is the leading cause of acute viral gastroenteritis across the world. Despite this, there are currently no vaccine or treatments available against norovirus. This project consists of two parts, focusing on two different protein drug targets of the norovirus.
The first protein target was the NS1-2 disordered protein. While the exact role of NS1-2 protein has not been discovered, it has been demonstrated in previous studies that the protein is crucial for virus replication. A ThermoFluor assay developed by our collaborators in Otago was used to screen a library of small molecules against the NS1-2 protein. Of the hit compounds, two were selected as lead compounds. Using the lead compounds, derivatives of the lead compounds were synthesised and sent to our collaborators so that they could be screened against NS1-2 protein in an attempt to develop a potent NS1-2 protein stabiliser while improving on the physiochemical properties of the small molecule. Four derivatives of the lead compounds were synthesised and tested against the recombinant NS1-2. Unfortunately, all four derivatives were ineffective against the NS1-2 protein.
The second protein was the norovirus 3CL protease. The norovirus 3CL protease cleaves the polyprotein encoded by the virus’ genome into their mature forms. The protease is also able to inhibit the translation of the host proteins by cleaving the poly(A)binding protein and thus allowing for more preferential viral protein expression. Utilizing a crystal structure reported by Hussey et al. in silico docking studies were conducted to design potential peptidomimetic inhibitors against the norovirus. Of the designed inhibitors, five peptides were chosen and synthesised. While one of the peptides were unable to be purified, the other four were synthesised, purified and sent to our collaborators for in vitro testing against the 3CL protease. |
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dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
Masters Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA |
en |
dc.rights |
Restricted Item. Full Text is available to authenticated members of The University of Auckland only. |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
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dc.title |
Synthesis of Antiviral Agents Targeting Norovirus |
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dc.type |
Thesis |
en |
thesis.degree.discipline |
Chemistry |
|
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Masters |
en |
dc.date.updated |
2021-10-28T03:14:17Z |
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dc.rights.holder |
Copyright: the author |
en |
dc.identifier.wikidata |
Q112955643 |
|