Bracken, Matthew Lee2024-10-162024-10-162023-08Bracken, 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/10539/41648https://hdl.handle.net/10539/41648A 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.The 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.en©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.Inorganic chemistryBiochemistry metal complexesPincers supramolecular chemistryXRDSARS-CoV-2COVID-19Fusion inhibitorsFluorescenceCD DFT docking dynamicsSchrodingerSpike proteinUCTDSDG-3: Good health and well-beingDissertationUniversity of the Witwatersrand, Johannesburg