Innovative Strategies for the Targeted Degradation of Viral Proteins: Paving the Way for Next-Generation Therapeutics

Background/Objectives: This review discusses the development and application of targeted protein degradation strategies, particularly focusing on the ubiquitin-proteasome pathway and PROteolysis-TArgeting Chimeras (PROTAC) technology, for antiviral therapies. Methods/Results: The synthesis of specific PROTACs exemplifies the potential of this approach to inhibit viral replication. The discussion also covers ongoing efforts to develop broad-spectrum antivirals and explores the limitations of small-molecule ligands, proposing antibody mimetics as a versatile alternative. The review details innovative strategies involving engineered antibody mimetics, termed 'diving antibodies' (DAbs), capable of intracellular delivery and targeting viral proteins within cells. These molecules are engineered using modular nanotransporters to facilitate intracellular delivery. The integration of E3 ligase-binding sites into DAbs enhances their capacity to induce targeted protein degradation, with experimental evidence supporting their efficacy. Conclusions: Overall, the review underscores the potential of combining targeted degradation technologies with innovative delivery systems to create effective antiviral therapies, especially for viruses with limited treatment options.