Recombinant ACE2 Variants Blocking SARS-CoV-2 Spike Protein Binding

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Solution Overview

Problem

There is a lack of effective therapies and personal protective equipment (PPE) to treat, ameliorate, or prevent COVID-19, particularly in preventing the SARS-CoV-2 virus from binding to human cells, which poses a significant risk to individuals with underlying medical conditions.

Innovation Solution

Development of recombinant variants of angiotensin-converting enzyme 2 (ACE2) with specific deletions and synthetic amino acid sequences that bind to the SARS-CoV-2 spike protein, including peptides with His-Tags, for use in therapeutic compositions and PPE to block viral entry into cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If recombinant ACE2 variants with specific deletions are used to block SARS-CoV-2 binding, then viral entry prevention is improved, but protein stability may be compromised

Engineering Contradiction:

Improveviral entry preventionVSAvoidprotein stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The ACE2 protein is segmented by deleting specific regions (residues 1-18 and 56-805) that are not critical for spike protein binding. This segmentation removes potentially unstable or redundant portions while preserving the functional binding domain, thereby improving viral entry prevention while maintaining adequate protein stability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The protein sequence parameters are changed by introducing specific deletions at defined positions. These parameter changes (deletions of specific amino acid residues) modify the protein's physical and functional properties to enhance binding affinity and stability against SARS-CoV-2 while maintaining overall structural integrity.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If synthetic amino acid sequences with His-Tags are developed, then binding activity to spike protein is improved, but manufacturing complexity increases

Engineering Contradiction:

Improvebinding activityVSAvoidmanufacturing complexity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

A His-Tag intermediary sequence is introduced into the synthetic amino acid sequences. This tag facilitates purification and characterization of the peptides during manufacturing while preserving the core binding activity. The tag acts as a mediator that simplifies downstream processing despite adding initial manufacturing steps.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The amino acid sequences are synthesized with specific modifications including His-Tag incorporation at defined positions. These parameter changes enable improved binding activity to the spike protein while the modular nature of synthetic peptide production keeps manufacturing complexity manageable through standardized synthesis protocols.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If PPE is designed to contain SARS-CoV-2, then transmission prevention is improved, but device complexity increases

Engineering Contradiction:

Improvetransmission preventionVSAvoidPPE structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The PPE is designed with integrated ACE2 binding components that provide multiple functions: viral containment, binding inhibition, and potential neutralization. This multi-functionality reduces the need for separate protective layers or devices, thereby preventing transmission while managing overall device complexity through consolidation of functions.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

ACE2 binding proteins serve as intermediaries incorporated into the PPE structure. These intermediaries capture and neutralize SARS-CoV-2 particles on the PPE surface, preventing viral transmission without requiring complex active systems. The intermediary molecules provide passive biochemical protection that simplifies the overall PPE design.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 described solutions effectively prevent SARS-CoV-2 from binding to human cells, providing a prompt and effective treatment, reducing the severity of COVID-19 symptoms, and offering prophylactic protection against SARS-CoV-2 infection, especially for individuals with comorbidities.

Implementation Method 1

spike proteins interact with human host cells by binding to angiotensin converting enzyme-2 (ACE-2) that is on the surface of these cells

Methodology Applied

Scientific EffectProtein-protein binding:

Implementation Method 2

the S2 protein mediates membrane fusion

Methodology Applied

Scientific EffectMembrane fusion:

Data Source

PatentUS20230235308A1Methods, compositions, and prophylactics for treating, ameliorating, or preventing coronavirus disease (covid-19)

Publication Date: 2023.07.27 THE RES FOUNDATION FOR THE STATE UNIV OF NEW YORK

AI summary

Disclosed are the methods and compositions for treating, ameliorating, or preventing COVID-19 or conditions associated with SARS-CoV-2 infection, and, also for reversing the damage caused by SARS-CoV-2 infection. Pharmaceutically acceptable compositions including spike protein binding partners, and optionally personal protective equipment included spike protein binding partners, are also disclosed.