Soutenance de thèse : Directed evolution of peptide inhibitors of influenza virus polymerase
Date
Vendredi 13 décembre 2024 de 14h00 à 17h30
Localisation
Salle des séminaires du bâtiment CIBB
Par Alberto Eduardo Florez Prada (IBS/Groupe Machines de Réplication Virale)
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.