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Updated: Nov 6, 2025

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
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ACE2-based decoy receptors for SARS coronavirus 2.

Wenyang Jing1, Erik Procko1,2

  • 1Center for Biophysics and Quantitative Biology, University of Illinois, Urbana, Illinois, USA.

Proteins
|May 11, 2021
PubMed
Summary

Engineered soluble angiotensin-converting enzyme 2 (ACE2) decoys show promise as broad-acting therapeutics against SARS-associated coronaviruses. These ACE2 derivatives offer dual mechanisms of action for treating COVID-19 and preventing related injuries.

Keywords:
ACE2COVID-19SARS coronavirus 2aviditydecoy receptorprotein engineering

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Area of Science:

  • Virology
  • Immunology
  • Biochemistry

Background:

  • SARS-CoV-2 utilizes spike proteins to bind the ACE2 receptor for cell entry.
  • Monoclonal antibodies are emerging therapies but have limitations in efficacy and viral escape.
  • Soluble ACE2 decoys present an alternative strategy for broad coronavirus neutralization.

Purpose of the Study:

  • To summarize advancements in engineering soluble ACE2 variants with enhanced affinity and potency.
  • To explore strategies for improving ACE2 decoy efficacy, including increased valency and pharmacokinetic optimization.
  • To highlight the dual mechanism of action of ACE2 derivatives in combating viral infection and host injury.

Main Methods:

  • Engineering higher affinity soluble ACE2 variants.
  • Increasing decoy valency for enhanced spike protein binding.
  • Developing IgG fusions to improve pharmacokinetics.

Main Results:

  • Engineered soluble ACE2 variants demonstrate potency rivaling affinity-matured antibodies.
  • Increased valency and IgG fusions enhance ACE2 decoy interactions with viral spikes.
  • ACE2's intrinsic enzymatic activity offers a dual mechanism against viral infection and associated organ damage.

Conclusions:

  • Soluble ACE2 derivatives represent a promising next-generation therapeutic for SARS-CoV-2 and future coronavirus outbreaks.
  • These decoys offer broad-spectrum neutralization with a lower potential for viral escape compared to antibodies.
  • The dual action of viral blocking and enzymatic activity provides a unique therapeutic advantage.