Fusion DNA Aptamers Blocking Spike-hACE2 Binding Across Variants
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Solution Overview
Problem
Current technologies lack effective inhibitors for SARS-CoV-2 variants that block the interaction between the coronavirus spike protein and the human angiotensin-converting enzyme 2 (hACE2) receptor, leading to respiratory issues and systemic inflammatory responses.
Innovation Solution
Development of DNA aptamers, specifically S1-specific, S2-specific, or fusion aptamers with poly A linkers, that bind to the spike protein to inhibit its interaction with hACE2, including variants like Delta and Omicron.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional inhibitors or vaccines are used, then some protection against coronavirus is achieved, but they are not effective against all variants and require continuous updates
Solution Approach 1:
The patent designs DNA aptamers that can bind to multiple regions of the spike protein (S1 subunit, S2 subunit, and S1S2 junction), enabling a single therapeutic agent to effectively inhibit various coronavirus variants including SARS-CoV-2, Delta, and Omicron. This universal binding capability allows the aptamers to maintain effectiveness across different viral variants without requiring continuous updates.
Solution Approach 2:
The patent employs fusion aptamers that combine multiple binding domains (S1-specific and S2-specific aptamers linked together) to create a composite molecular structure. This composite design enables simultaneous recognition of different spike protein regions, enhancing the inhibitor's ability to counter various coronavirus variants effectively.
2Adaptability or versatility
If broad-spectrum inhibitors are developed to work against all variants, then versatility is improved, but the complexity of designing and testing increases
Solution Approach 1:
The patent divides the spike protein into distinct functional regions (S1 subunit, S2 subunit, and S1S2 junction) and designs separate aptamers targeting each region. This segmentation allows independent optimization of each aptamer's binding characteristics while maintaining overall effectiveness against multiple variants, simplifying the design process compared to creating a single complex binder.
Solution Approach 2:
The patent merges S1-specific and S2-specific aptamers into fusion aptamers through linker sequences, creating chimeric molecules that possess both binding capabilities. This merging strategy combines the advantages of region-specific targeting while presenting a unified molecular structure that simplifies administration and reduces the need for multiple separate therapies.
3Measurement precision
If multiple separate aptamers targeting different spike protein regions are used, then binding specificity is improved, but the complexity of administration increases
Solution Approach 1:
The patent combines multiple aptamers (S1-specific and S2-specific) into single fusion aptamer molecules through covalent linkage. This merging maintains the high binding specificity of individual aptamers while simplifying administration to a single therapeutic agent, eliminating the need to administer multiple separate compounds and their respective dosing regimens.
Solution Approach 2:
The fusion aptamers are designed to perform multiple functions simultaneously: binding to different spike protein regions, preventing viral entry, and maintaining effectiveness across variants. This multi-functionality in a single molecule reduces the complexity of therapeutic administration while preserving the specificity needed for effective viral inhibition.
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 DNA aptamers effectively block the spike protein-hACE2 interaction, providing a therapeutic and diagnostic tool for coronavirus infections and neutralizing the virus, with broad applicability across variants.
Implementation Method 1
the DNA aptamer binds to a spike protein of the coronavirus
Data Source
AI summary
Compositions, methods of inhibiting binding between a coronavirus and a MACE2 receptor, methods of treating a coronavirus infection, methods of diagnosing a coronavirus infection, and kits for diagnosing a coronavirus infection, all involving contacting a hACE2 receptor with a DNA aptamer to block binding to the receptor, wherein the DNA aptamer binds to a spike protein of the coronavirus, are described.