ACE2-Binding Aptamers for Blocking SARS-CoV-2 Cell Entry

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Solution Overview

Problem

Existing approaches to combat SARS-CoV-2 infection primarily focus on neutralizing the virus through vaccination, whereas the virus's entry into cells via the ACE2 receptor is not adequately addressed, allowing for unchecked replication and spread.

Innovation Solution

Development of oligonucleotides, specifically aptamers, that selectively block the interaction between the viral Spike protein and the ACE2 receptor, inhibiting the initial Spike-ACE2 interaction to protect target cells from virus aggression and subsequent infection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If vaccination is used to neutralize the virus, then viral infection is reduced, but the virus's entry mechanism via ACE2 receptor is not adequately addressed

Engineering Contradiction:

Improveviral infection preventionVSAvoidvirus entry through ACE2

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces aptamers as intermediary molecules that bind to the ACE2 receptor, blocking the viral Spike protein from interacting with the receptor. This mediator approach directly addresses the harmful entry mechanism while maintaining the benefits of existing vaccination strategies.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The aptamers perform preliminary blocking action by pre-binding to the ACE2 receptor before the virus can attach. This preliminary anti-action prevents the harmful interaction between the Spike protein and ACE2, stopping infection at the entry stage rather than addressing it after vaccination has neutralized the virus.

Inventive Principle:

Principle #9Preliminary anti-action

2Object-affected harmful factors

If the Spike-ACE2 interaction is blocked, then viral entry is prevented, but the mechanism requires selective binding to specific residues

Engineering Contradiction:

Improveviral entry and replicationVSAvoidbinding specificity to K353 residue

Core Design Contradiction:

Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent applies local quality by designing aptamers that specifically target the K353 residue region on the ACE2 receptor, where the Spike protein binds. This localized binding approach prevents viral entry while maintaining compatibility with other regions of the receptor that may have different functions.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention utilizes parameter changes by modifying the binding characteristics of the aptamers to achieve high specificity for the K353 residue. Through optimization of the aptamer sequence and structure, the binding affinity and specificity parameters are tuned to selectively block the Spike-ACE2 interaction at the critical interaction site.

Inventive Principle:

Principle #35Parameter changes

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 aptamers effectively inhibit the Spike-ACE2 interaction, preventing viral entry and replication, demonstrating efficacy against various SARS-CoV-2 variants and other coronaviruses, including SARS-CoV and HCoC-NL63, by binding to the ACE2 receptor and blocking the viral Spike protein, particularly at the K353 residue.

Implementation Method 1

compounds capable of binding to the human protein ACE2 and inhibiting the interaction between the viral protein SPIKE and the human protein ACE2

Methodology Applied

Scientific EffectMolecular binding:

Data Source

PatentUS20250304972A1Compounds for inhibiting the interaction of SARS-COV2 with human protein ace2

Publication Date: 2025.10.02 UNIV DELGI STUDI DI MILANO

AI summary

Novel compounds capable of blocking viral infections sustained by the SARS-Cov2 virus are provided. A method for preventing and/or treating infectious diseases caused by a virus involving administering the novel compounds is also provided.