Fusion Proteins Blocking Flavivirus Receptor Binding
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Solution Overview
Problem
Current methods struggle to effectively identify and modulate the binding of pathogens like dengue virus and Japanese encephalitis virus to their respective receptors, leading to excessive inflammation and poor treatment outcomes.
Innovation Solution
Development of fusion proteins comprising a carbohydrate recognition domain of innate immunity receptors and a heterologous polypeptide, which can bind to pathogens and inhibit receptor binding, thereby reducing pro-inflammatory cytokine secretion without affecting viral clearance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If fusion proteins are used to block pathogen-receptor binding, then pro-inflammatory cytokine secretion is reduced, but viral clearance may be affected
Solution Approach 1:
The patent introduces fusion proteins as intermediary molecules that specifically bind to pathogens (dengue virus, Japanese encephalitis virus) and block their interaction with cellular receptors (DLVR1/CLEC5A). These fusion proteins act as mediators that prevent the harmful signaling pathway while allowing the immune system to clear the virus through other mechanisms, thus resolving the contradiction between reducing inflammation and maintaining viral clearance
2Ease of operation
If conventional methods are used to treat flavivirus infection, then treatment is simple, but excessive inflammation occurs and treatment outcomes are poor
Solution Approach 1:
The fusion proteins serve as targeted intermediaries that specifically intervene in the pathogen-receptor interaction pathway. By blocking the binding between flaviviruses and DLVR1/CLEC5A receptors, these fusion proteins prevent the downstream inflammatory signaling cascade without requiring complex immunosuppressive regimens, thus reducing excessive inflammation while maintaining treatment simplicity
Solution Approach 2:
The patent modifies the inflammatory response parameter by introducing fusion proteins that specifically alter the binding affinity between pathogens and receptors. This parameter change (blocking specific interactions) leads to reduced pro-inflammatory cytokine secretion while maintaining the body's ability to clear viruses through unchanged immune mechanisms
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 use of these fusion proteins effectively inhibits TNF-α secretion and reduces inflammation, increasing survival rates in infected mice by blocking the binding of pathogens to their receptors, thus modulating the immune response.
Implementation Method 1
the host immune system can recognize invasive pathogens through specific carbohydrate antigens. For example, mannose receptors can recognize the high mannose sugar moiety expressed on the surface of pathogens
Implementation Method 2
contacting the fusion protein with a pathogen to determine if the pathogen binds to the binding domain of at least one fusion protein of the complement of fusion proteins
Data Source
AI summary
Cellular receptors are identified that induce plasma leakage and other negative effects when infected with flaviviruses, such as dengue virus or Japanese encephamyelitis virus. Using fusion proteins disclosed herein, the receptors to which a pathogen, such as flavivirus, binds via glycan binding are determined. Once the receptors are determined, the effect of binding to a particular receptor may be determined, wherein targeting of the receptors causing a particular symptom may be targeted by agents that interrupt binding of the pathogen to the receptor. Accordingly, in the case of dengue virus and Japanese encephamyelitis virus, TNF-α is released when the pathogen binds to the DLVR1/CLEC5A receptor. Interrupting the DLVR1/CLEC5A receptor with monoclonal antibodies reduced TNF-α secretion without affecting secretion of cytokines responsible for viral clearance thereby increasing survival rates in infected mice from nil to around 50%.