Electronic Theses and Dissertations (PhDs)

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Browsing Electronic Theses and Dissertations (PhDs) by School "School of Geography, Archaeology and Environmental Sciences"

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    Computational modeling approaches to validate the druggability of the 26- and 28-kDa Schistosoma glutathione transferase enzymes using bromosulfophthalein as a benchmark ligand
    (University of the Witwatersrand, Johannesburg, 2024) Valli, Akeel
    PHARMACOPHORE MODELS are 3-D representations of the chemical and spatial features required for interaction with a drug target. These. models offer advantages in early-phase drug design by expediting screening experiments and enabling the sampling of highly specific chemical. space subsets, such as those containing quality drug-like candidates. The glutathione transferase enzyme of Schistosoma spp. (SGST) has been identified as an attractive drug target for the novel treatment of human schistosomiasis. We observed selective inhibition of SGST by bromosulfophthalein. Bromosulfophthalein was found to complex with SGST at a drug binding site in the target dimer interface, providing a suitable benchmark for the design of discriminative SGST pharmacophores. The aim of this research is to construct, deploy and evaluate pharmacophore models of the SGST drug binding site. The objectives are: to characterise the SGST drug binding site, to develop the pharmacophore models and finally to evaluate the drug-resolving ability of the models. We observed significant differences in the drug-binding character of SGST, compared to human glutathione transferase (hGST) counterparts, particularly that SGST supports binding of phenol and sulfonate moieties. Five- and four feature pharmacophores were developed for the respective 26- and 28 kDa SGST variants. Finally, the models demonstrated remarkable ability to retrieve candidates displaying drug-like qualities. In conclusion, we characterised and developed pharmacophore models of the drug binding domains from two major SGST variants. Assessment of drug-resolving power validates the capability of the models to sample drug-like chemicals. Altogether, these accomplishments enable efficient and reliable screening toward novel drug treatment for human schistosomiasis
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    Moving towards landscape initiatives: an analysis of environmental frameworks, protected areas, and community perspectives in the vhembe district, limpopo province, South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Dalziel, Alexandra; Evans, Mary
    ConservaBon strategies have shiMed towards a landscape-centric approach, emphasising conservaBon corridors and ecological networks. However, exploraBon of these strategies within the South African context is incomplete. This research aims to address this gap by applying various methods, including a systemaBc literature review, policy analysis, spaBal analysis using GIS, and conducBng interviews and surveys, resulBng in four key contribuBons invesBgaBng the potenBal for conservaBon corridors and networks. The first is a comprehensive literature review underscoring the significance of corridors and networks while highlighBng the discourse surrounding these emerging approaches in South Africa. The findings revealed a substanBal global interest in landscape iniBaBves. However, South Africa’s contribuBon is geographically limited, with 82% of studies focusing on the KwaZulu-Natal province. Understanding the efficacy of these studies in South Africa necessitates a comprehensive examinaBon of the underlying regulatory frameworks governing protected areas and conservaBon efforts. Therefore, the second contribuBon evaluated protected areas and conservaBon legislaBon and policies to assess their alignment with landscape-focused iniBaBves. The study reveals a lack of explicit provisions supporBng landscape-based conservaBon methods. The third study draws on these findings and uses the Vhembe District in the Limpopo Province as a case study to illustrate the overlooked potenBal of landscape iniBaBves. IniBally, the protected areas in the district were evaluated. Subsequently, the analysis employed Key and CriBcal Biodiversity Areas to highlight the inadequacies within the exisBng protected area network. The findings revealed that although protected areas cover 38% of the Vhembe District, over 70% of CriBcal Biodiversity Areas and 60% of Key Biodiversity Areas lack protecBon. Over 2,000 km2 of unprotected CriBcal and Key Biodiversity Areas were idenBfied along the Soutpansberg Mountain Range and marked as ideal for a conservaBon corridor. The fourth contribuBon centres on community engagement, an essenBal consideraBon for sustainable long-term conservaBon. The results underscored strong community support for a corridor in the Vhembe District, primarily moBvated by the anBcipated socio-economic benefits. However, while landscape iniBaBves promise socio-economic improvement, such outcomes are not guaranteed. Moreover, other potenBal challenges, including development, land rights, and financial constraints, were idenBfied as possible impediments to corridors in the Vhembe District. The invesBgaBon into corridors and networks in South Africa, specifically the Vhembe District, revealed that the discourse on landscape iniBaBves is in its nascent phase. Nevertheless, when prioriBsing community engagement, these iniBaBves harbour tremendous potenBal. New legislaBon and policies that account for these factors will guide proponents of these iniBaBves and propel landscape iniBaBves into South Africa’s conservaBon toolbox.