Dr. Lawrence Harris (Institute: Ferrier Research Institute (Victoria University of Wellington)) will give a lecture titled “The Development of New Classes of Antiviral Nucleoside” on Monday, June 8, at 10:30 a.m. in the Marie Curie Room.
Summary
Broad-spectrum antiviral nucleosides are an important class of molecules with proven potential to treat viral diseases. Both RNA and DNA viruses are susceptible to these modified nucleotides that interfere with viral nucleic acid replication. This talk outlines our efforts to develop two new classes of broad-spectrum antivirals (BSAs) based on (i) Galidesivir (Immucillin A, BCX4430) – a known synthetic imino-C-nucleoside with broad-spectrum activity, and (ii) the recently discovered, antiviral ribonucleotide product of the interferon-inducible protein viperin, namely 3’-deoxy-3’,4’-didehydrocytidine triphosphate (ddhCTP).
Broad screening of novel compounds for antiviral activity in cell-based assays reveals that subtle modifications to the nucleobase component of imino-C-nucleosides can profoundly enhance or reduce the activity. One compound that exhibited sub-micromolar activity against multiple strains of influenza A and B viruses and excellent selectivity indexes was assessed against influenza A (H1N1) in preliminary in vivo studies in BALB/c mice. However, it displayed significant toxicity necessitating further development. Through further synthetic modification, attempts to lower the intrinsic toxicity of this molecule have delivered new compounds with improved safety profiles in vitro. Work is ongoing to further develop these promising new antiviral leads.