Soluble ACE2 Decoy Receptor for SARS-CoV-2 Infection
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Solution Overview
Problem
Current treatments for SARS-CoV-2 infections lack specificity and may have undesirable side effects due to targeting ACE2, necessitating a more targeted approach to prevent or treat infections without disrupting the physiological roles of ACE2.
Innovation Solution
Administering a recombinant Angiotensin converting enzyme 2 (rACE2), specifically a soluble, glycosylated, and potentially dimeric form of ACE2, to interfere with the virus's entry into host cells by binding to the spike protein's receptor binding domain, thereby inhibiting infection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If disruptive agents targeted to ACE2 are used to inhibit SARS-CoV infection, then viral entry is blocked, but ACE2 physiological functions are disrupted causing undesired side effects
Solution Approach 1:
The patent employs a soluble ACE2 fusion protein as an intermediary decoy that binds to the SARS-CoV spike protein-RBD complex, preventing viral attachment to cellular ACE2 receptors while leaving cellular ACE2 physiology intact. The fusion protein comprises the extracellular domain of human ACE2 (amino acids 1-608) fused to the Fc region of human IgG1, creating a soluble decoy receptor that sequesters viral particles without disrupting endogenous ACE2 function in host cells.
2Strength
If ACE2 expression is increased to protect from lung injury, then lung protection is enhanced, but viral entry is facilitated worsening infection severity
Solution Approach 1:
The patent applies preliminary anti-action by administering soluble ACE2 fusion protein before or during viral infection to preemptively block viral attachment. The fusion protein circulates in the bloodstream and binds to incoming SARS-CoV particles, preventing them from reaching and infecting ACE2-expressing lung cells. This allows the host to maintain or increase ACE2 expression for lung protection without the trade-off of increased viral susceptibility.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The administration of rACE2 effectively inhibits SARS-CoV-2 infection in vitro by blocking viral attachment and replication, demonstrating a targeted and specific mechanism of action with minimal cytotoxicity, as shown in cell and organoid models.
Implementation Method 1
Administering a recombinant Angiotensin converting enzyme 2 (rACE2), specifically a soluble, glycosylated, and potentially dimeric form of ACE2, to interfere with the virus's entry into host cells by binding to the spike protein's receptor binding domain
Data Source
AI summary
Provided herein are methods for treating or preventing infection of a subject by a virus that infects the subject through angiotensin converting enzyme 2.