A computational exploration of the genomic and structural evolution of SARS-CoV-2

Mack, Andrew 2024. A computational exploration of the genomic and structural evolution of SARS-CoV-2. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Since its emergence in late 2019, the SARS-CoV-2 virus has been linked to the deaths of over 7 million people worldwide, accompanied by unparalleled economic and societal disruption. Despite monumental efforts by scientists that facilitated the rapid development of vaccines to prevent severe outcomes from the virus, SARS-CoV-2 continues to evolve and acquire mutations that reduce vaccine efficacy and enhance transmissibility. Considering this, the research presented explores the evolution of the SARS-CoV-2 virus through the analysis of genomic data. The implications of these mutations are further investigated using biophysical simulations. Chapter 3 characterizes regions of the spike protein under selective pressure and associated with the loss of glycosylation within the furin cleavage site. The impact of this loss on the dynamic nature of the spike protein is examined, suggesting long-range structural implications. Chapter 4 employs co-evolutionary analyses to identify mutations in the membrane protein that are exclusive to specific SARS-CoV-2 lineages and do not co-occur. The effects of these mutations on interactions with membrane components are investigated using coarse-grain and all-atom simulations, revealing varying cholesterol-binding capacities of the membrane protein in SARS-CoV-2 variants. The recent publication, “A Proofreading Mutation with an Allosteric Effect Allows a Cluster of SARS-CoV-2 Viruses to Rapidly Evolve,” is presented in Chapter 5. This work demonstrates that a cluster of viruses with a mutation at the interface of the SARS-CoV-2 proofreading enzyme and its cofactor, NSP10, is associated with an increased mutation rate

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	13 May 2025
Last Modified:	13 May 2025 18:02
URI:	https://orca.cardiff.ac.uk/id/eprint/178227

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