Soluble CDHR3 Protein Fragments for RV-C Entry Blocking
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Solution Overview
Problem
Rhinovirus C (RV-C) viruses are difficult to propagate in conventional cell culture systems and lack effective antiviral treatments, leading to severe respiratory infections, particularly in children, as they utilize cadherin related family member 3 (CDHR3) as a cellular receptor, which is not well understood for viral entry and infectivity.
Innovation Solution
Development of soluble truncated CDHR3 peptides, including domain 1 and optionally domain 2 or 3, with specific linkers and mutations, which inhibit RV-C binding and viral infectivity, and can be used in therapeutic compositions and in vitro assays for antiviral drug screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional cell culture systems are used to propagate rhinovirus C, then standard viral propagation methods can be applied, but RV-C replication is not detectable and virus propagation fails
Solution Approach 1:
The patent uses soluble CDHR3 protein as an intermediary to facilitate RV-C propagation. The soluble CDHR3 acts as a decoy receptor that binds to RV-C viruses, enabling their detection and propagation in cell culture systems where they would otherwise be undetectable. This intermediary approach allows standard cell culture methods to successfully propagate RV-C by providing the necessary receptor function in a soluble form.
2Object-affected harmful factors
If full-length CDHR3 protein is used to block viral entry, then viral infectivity can be inhibited, but the protein is membrane-bound and difficult to produce as a therapeutic agent
Solution Approach 1:
The patent extracts the extracellular domain (ECD) of CDHR3 from the full-length membrane-bound protein to create a soluble therapeutic agent. By taking out only the functional extracellular portion that binds to RV-C, the invention creates a soluble truncated CDHR3 protein that can be easily produced recombinantly and administered therapeutically, while retaining the ability to block viral entry.
Solution Approach 2:
The patent segments the CDHR3 protein into distinct functional domains, specifically isolating the extracellular domain that mediates viral binding. This segmentation allows the therapeutic agent to be produced as a soluble fragment rather than the complete membrane-bound protein, facilitating easier manufacturing and administration while maintaining antiviral activity.
3Ease of manufacture
If soluble truncated CDHR3 peptides are developed for therapy, then ease of production improves, but the structural complexity must be carefully controlled to maintain function
Solution Approach 1:
The patent applies local quality by focusing the therapeutic activity in a specific structural region - the extracellular domain of CDHR3. By concentrating the functional elements in this localized region and truncating the rest of the protein, the invention achieves both ease of recombinant production and maintained viral binding function, as the critical structural elements are preserved in the ECD portion.
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 soluble truncated CDHR3 peptides effectively block RV-C virus binding and replication, providing a basis for antiviral therapies and in vitro screening assays, specifically targeting RV-C strains associated with childhood asthma exacerbations and severe respiratory infections.
Implementation Method 1
The soluble truncated CDHR3 peptides effectively block RV-C virus binding and replication
Data Source
AI summary
The present invention provides soluble truncated peptides of CDHR3, recombinant variants thereof and methods of making these peptides. The present invention also provide methods of inhibiting rhinovirus C infection and an in vitro assay for screening for anti-viral agents against rhinovirus C.