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Antiviral PROTACs: Opportunity borne with challenge
Jinsen Liang1, Yihe Wu2, Ke Lan3
1Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430071, China.
Cell Insight
|July 3, 2023
Summary
Proteolysis targeting chimeras (PROTACs) offer a novel antiviral strategy, but challenges like limited ligands and viral mutation hinder development. This review explores advances and limitations in antiviral PROTACs.
Area of Science:
- Biochemistry
- Drug Discovery
- Virology
Background:
- Proteolysis targeting chimeras (PROTACs) leverage the ubiquitin-proteasome system for targeted protein degradation.
- PROTAC technology is rapidly advancing, with numerous candidates in clinical trials for various diseases.
- Antiviral PROTACs show promise but lag behind other therapeutic areas due to specific challenges.
Purpose of the Study:
- To review the current advancements in antiviral PROTACs and related agents.
- To identify and analyze critical limitations hindering the development of effective antiviral PROTACs.
- To summarize design principles and optimization strategies for future antiviral PROTAC development.
Main Methods:
- Literature review of current antiviral PROTACs and PROTAC-like agents.
- Analysis of representative examples and their bioactivities.
- Examination of common PROTAC deficiencies and viral mutation challenges.
Main Results:
- Several antiviral PROTACs have demonstrated promising bioactivities against various viruses.
- Key limitations include limited ligand availability, poor membrane permeability, complex mechanisms, and viral mutation rates.
- The field is rapidly growing, but the number of antiviral PROTACs remains limited compared to other disease areas.
Conclusions:
- Antiviral PROTACs represent a promising therapeutic avenue, but significant hurdles remain.
- Overcoming technical and biological challenges is crucial for successful antiviral PROTAC development.
- Strategic design and optimization are essential for advancing future antiviral PROTAC research and application.
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