TY - JOUR
T1 - Antiviral strategies based on targeted protein degradation
T2 - An overview of the literature and future outlook
AU - Zhou, Fan
AU - Shi, Dazhou
AU - Li, Baohu
AU - Wang, Mei
AU - Xu, Shujing
AU - Yang, Jinfei
AU - Deng, Xu
AU - Zhan, Peng
N1 - Publisher Copyright:
© 2025 Elsevier Masson SAS
PY - 2026/1/5
Y1 - 2026/1/5
N2 - 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.
AB - 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.
KW - Antiviral therapy
KW - Drug resistance
KW - Host factor
KW - PROTAC
KW - Targeted protein degradation
KW - Viral protein degradation
UR - https://www.scopus.com/pages/publications/105017632056
U2 - 10.1016/j.ejmech.2025.118208
DO - 10.1016/j.ejmech.2025.118208
M3 - 文献综述
AN - SCOPUS:105017632056
SN - 0223-5234
VL - 301
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
M1 - 118208
ER -
