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Engineering ACE2 decoy receptors to combat viral escapability.
Takao Arimori1, Nariko Ikemura2, Toru Okamoto3
1Laboratory for Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.
Trends in Pharmacological Sciences
|July 28, 2022
Summary
Soluble ACE2 decoy receptors show promise against coronaviruses, including COVID-19. Enhancements like high-affinity mutagenesis and aerosol delivery may boost efficacy and immune response.
Area of Science:
- Virology
- Immunology
- Biotechnology
Background:
- Angiotensin-converting enzyme 2 (ACE2) is a key receptor for coronavirus entry.
- Recombinant soluble ACE2 has a history of safe clinical use for acute respiratory distress syndrome (ARDS).
Purpose of the Study:
- To review advancements in recombinant ACE2 decoy receptors for broad-spectrum coronavirus defense.
- To explore strategies for enhancing therapeutic efficacy and delivery methods.
Main Methods:
- High-affinity mutagenesis to improve ACE2 binding.
- Fc fusion techniques to enhance protein stability and effector functions.
- Preclinical studies evaluating efficacy against coronaviruses.
Main Results:
- Engineered ACE2 decoys demonstrate potential for broad-spectrum antiviral activity.
- Fc fusion may stimulate immune cells, augmenting therapeutic effects.
- Liquid aerosol delivery is a promising strategy for respiratory viral infections.
Conclusions:
- Recombinant ACE2 decoy receptors offer a promising therapeutic strategy against ACE2-utilizing coronaviruses.
- Further development focuses on optimizing binding affinity, immune engagement, and delivery for enhanced protection.
