Hydrogenases, enzymes that catalyze the reversible conversion of protons and electrons into molecular hydrogen, offer promising avenues for sustainable energy production. My research centered on the roles of HydE and HydG, two essential maturase enzymes responsible for assembling the active site of [FeFe] hydrogenases, specifically the formation of the H-cluster, which is critical to the enzyme’s catalytic function. ​
Influenza remains a significant threat to human and animal health. New antiviral drugs are needed due to rapid resistance to existing treatments. This thesis focuses on designing peptides to inhibit the assembly of the viral RNA polymerase. The N-terminal 15 amino acid motif of the PB1 subunit interacts with the PA subunit, and when synthesised as a peptide, it reduces viral replication. Using phage display, next-generation sequencing, and neural network design, we identified peptides mimicking this motif with enhanced binding affinity. X-ray analysis and alanine scanning revealed key features of the improved peptides. Cellular assays showed a marked reduction in influenza polymerase activity and viral replication in human pulmonary cells, outperforming the wild-type peptide. This work describes advances in the disruption of protein-protein interactions, underscoring the potential of peptide-based antivirals.​
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