Metal Pincers as Antiviral Agents Targeting SARS-CoV-2 Spike Protein

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dc.contributor.authorBracken, Matthew Lee
dc.contributor.supervisorMunro, Orde Q.
dc.date.accessioned2024-10-16T12:13:28Z
dc.date.available2024-10-16T12:13:28Z
dc.date.issued2023-08
dc.descriptionA research report submitted in partial fulfilment of the requirements for the Degree of Master of Science, School of Chemistry, at the University of the Witwatersrand, Johannesburg, 2023.
dc.description.abstractThe purpose of this work was to prove the concept that complexes of bioavailable metal ions may be designed to target specific solvent-exposed amino acid residues on therapeutic protein targets. The complexes synthesized and studied were novel Zn(II) and Cu(II) NNN amide pincers. The chelates were designed by in silico methods to target solvent-exposed tyrosine residues on the receptor binding domain of SARS-CoV-2. These tyrosine residues are crucial for binding host cell receptors and by targeting these groups, the metal pincers may potentially act as antiviral fusion inhibitors for the treatment of COVID-19. Biophysical studies were carried out to determine the binding affinity between the chelate and phenolic residues. These studies identified the most likely binding site for the metal complex on the SARS-CoV-2 spike protein epitope. The novel chelates were crystalized and found to adopt hexameric metallocycle architecture.
dc.description.sponsorshipNational Research Foundation (NRF).
dc.description.sponsorshipFunding granted by Prof. Munro.
dc.description.sponsorshipUniversity of the Witwatersrand, Johannesburg.
dc.description.submitterMM2024
dc.facultyFaculty of Science
dc.identifier0000-0003-2336-1469
dc.identifier.citationBracken, Matthew Lee. (2023). Metal Pincers as Antiviral Agents Targeting SARS-CoV-2 Spike Protein. [Master's dissertation, University of the Witwatersrand, Johannesburg]. https://hdl.handle.net/10539/41648
dc.identifier.urihttps://hdl.handle.net/10539/41648
dc.language.isoen
dc.publisherUniversity of the Witwatersrand, Johannesburg
dc.rights©2023 University of the Witwatersrand, Johannesburg. All rights reserved. The copyright in this work vests in the University of the Witwatersrand, Johannesburg. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of University of the Witwatersrand, Johannesburg.
dc.rights.holderUniversity of the Witwatersrand, Johannesburg
dc.schoolSchool of Chemistry
dc.subjectInorganic chemistry
dc.subjectBiochemistry metal complexes
dc.subjectPincers supramolecular chemistry
dc.subjectXRD
dc.subjectSARS-CoV-2
dc.subjectCOVID-19
dc.subjectFusion inhibitors
dc.subjectFluorescence
dc.subjectCD DFT docking dynamics
dc.subjectSchrodinger
dc.subjectSpike protein
dc.subjectUCTD
dc.subject.otherSDG-3: Good health and well-being
dc.titleMetal Pincers as Antiviral Agents Targeting SARS-CoV-2 Spike Protein
dc.typeDissertation
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