Biosensing Platform for ACE2-Spike Protein Interaction Screening

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Solution Overview

Problem

There is an unmet need to identify competent compounds that can effectively treat coronavirus infections, particularly given the concern that pharmacological inducers of ACE2 expression, such as ACE inhibitors, may increase the infection risk or exacerbate the severity of SARS-CoV-2 infection.

Innovation Solution

A biosensing platform is developed to screen modulators that can modulate the protein-protein interaction between coronavirus S-protein and ACE2 on the host cell surface, thereby protecting a subject from viral infection. The modulators are represented by specific chemical formulas (I, II, and III) and include compounds like perindopril, enalapril, and lisinopril.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ACE2 expression is induced using pharmacological agents such as ACE inhibitors, then the host cell's capacity to handle angiotensin II is improved, but the risk of viral infection increases due to enhanced binding of coronavirus S-protein to ACE2

Engineering Contradiction:

Improvehost cell capacity to handle angiotensin IIVSAvoidviral infection risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses a biosensing platform as an intermediary tool to screen and identify modulators that can differentiate between beneficial ACE2 induction and harmful viral binding. The platform mediates the detection of S-protein-ACE2 interactions, enabling the selection of compounds that modulate ACE2 function without increasing infection risk.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the parameter of ACE2 modulation by identifying compounds that alter ACE2 expression or function in a controlled manner. The biosensing platform enables detection of subtle changes in ACE2-S-protein binding affinity, allowing selection of modulators that achieve therapeutic ACE2 induction while maintaining safe binding characteristics.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If a biosensing platform is developed to screen modulators, then the ability to identify competent compounds is improved, but the device complexity increases

Engineering Contradiction:

Improveability to identify competent compoundsVSAvoidbiosensing platform structure

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical screening methods with an electrochemical biosensing platform. The system uses electrochemical impedance spectroscopy to detect molecular interactions, substituting physical/mechanical assay methods with electrical measurement techniques that provide higher precision with relatively simplified device architecture.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The biosensing platform is designed with multi-functionality, serving both as a diagnostic tool for detecting viral infections and as a screening platform for identifying modulators. This universal design reduces overall system complexity by consolidating multiple functions into a single platform rather than requiring separate systems.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 modulators identified by the biosensing platform can effectively inhibit the entry of viruses into host cells, reducing the risk or severity of viral infections. Additionally, these compounds can enhance the immunogenicity of vaccine compositions, improving the immune response against the virus.

Implementation Method 1

The interaction of the S-protein with the ACE2 was then assessed by measuring the charge transfer resistance at the electrode surface using electrochemical impedance spectroscopy

Methodology Applied

Scientific EffectElectrochemical impedance spectroscopy:

Implementation Method 2

The structural proteins of CoVs include nucleocapsid (N), small envelope (E), matrix (M) and trimeric spike (S) glycoproteins, which are essential for virion assembly and function to complete the viral life cycle during infections

Methodology Applied

Scientific EffectEnzyme inhibition:

Data Source

PatentUS12201613B2Biosensing platform for detecting viral infections and methods for screening a modulator of viral infections and protecting therefrom

Publication Date: 2025.01.21 PIN JYE BIO TECH CO LTD

AI summary

Provided is a method for screening a modulator of a viral infection by detecting an interaction of angiotensin converting enzyme 2 (ACE2) and a spike protein with a biosensing platform. Also provided is a compound of formula (I) as a modulator of a viral infection, where R, X, A, R3 to R5, and m are as defined herein, and a method for protecting a subject from a viral infection by administering with the compound.