Antiviral strategies based on targeted protein degradation: An overview of the literature and future outlook.

Viral infections persist as global threats, with traditional therapies limited by resistance and narrow targets. This review highlights targeted protein degradation (TPD) as a transformative antiviral strategy, covering proteolysis-targeting chimeras (PROTACs), hydrophobic tagging (HyT), and lysosome-targeting chimeras (LYTACs) against Influenza A virus (IAV), Human immunodeficiency virus (HIV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV). TPD's "event-driven" mechanism degrades "undruggable" viral/host proteins (e.g., PA, HDAC6) to bypass resistance. Key breakthroughs include PROTAC vaccines (106-fold titer reduction) and liver-targeted degraders. It addresses pharmacokinetic/off-target challenges, proposing multi-target strategies and organ-specific delivery to redefine antiviral therapy from passive control to active eradication.