Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics

Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC) is an emerging drug discovery platform. PROTAC molecules, which typically contain a target protein ligand linked to an E3 ligase ligand, recruit a target protein to the E3 ligase to induce its ubiquitination and degradation. Here, we applied PROTAC approaches to develop broad-spectrum antivirals targeting key host factors for many viruses and virus-specific antivirals targeting unique viral proteins.