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A comparative analysis of similar respiratory viruses to determine a cause for their differential phenotypes

Thorpe, Charlotte (2022) A comparative analysis of similar respiratory viruses to determine a cause for their differential phenotypes. Master of Science by Research (MScRes) thesis, University of Kent,. (doi:10.22024/UniKent/01.02.96740) (KAR id:96740)

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Official URL:
https://doi.org/10.22024/UniKent/01.02.96740

Abstract

Pandemic viruses have plagued humanity since records began. Recent years have seen viruses re-emerge from the past with high sequence identity to previous strains despite significant differences in virulence and pathogenicity. This research focuses on two different viruses. Firstly, investigating the determinants of pathogenicity in influenza A(H1N1) using a novel approach developed at the University of Kent to identify differentially conserved positions (DCPs). DCPs are specific positions within the virus protein that are one amino acid in group 1 and a different amino acid in group 2, meaning they have no structural purpose but may play a role in pathogenicity. This will be explored as it may explain how differences in pathogenicity can arise between related viruses. Secondly, this project considers the adaptation of SARS-CoV-2 to the serine protease drugs camostat and nafamostat by analysing sequence data provided by collaborators at Frankfurt University. N233S, T293I, and Q250P are three influenza A(H1N1) DCPs that were concluded to cause likely effects to the protein structure or function and therefore, may well be causing the differences in phenotypes and therefore the differences in disease severity. Furthermore, S50L, A222V, D614G, A653V, T732I and A879V are SARS-CoV-2 spike protein mutations that were found to cause likely effects to the protein structure or function, signifying they may contribute to resistance to camostat or nafamostat. This project has found several mutations of interest between closely related viruses that provides insight as to how mutations in viral genomes can cause differences in phenotypes.

Item Type: Thesis (Master of Science by Research (MScRes))
Thesis advisor: Wass, Mark
Thesis advisor: Michaelis, Martin
DOI/Identification number: 10.22024/UniKent/01.02.96740
Uncontrolled keywords: influenza, virus, camostat, nafamostat, SARS-CoV-2
Subjects: Q Science > QP Physiology (Living systems)
Q Science > QR Microbiology
Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 05 Sep 2022 08:10 UTC
Last Modified: 26 Sep 2022 09:22 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/96740 (The current URI for this page, for reference purposes)
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