Retro-Inverso Peptide RI57 for Flavivirus Entry Inhibition
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Solution Overview
Problem
Current treatments for flavivirus infections, such as dengue and Zika, lack effective specific therapeutics, and existing peptides are susceptible to degradation by peptidases, limiting their administration to non-oral routes, which is undesirable for widespread use, especially in areas with limited medical access.
Innovation Solution
Development of enantiopure, protease-resistant peptides, like RI57, that specifically bind to flavivirus class II E protein regions, inhibiting virus entry into host cells and are resistant to peptidase degradation, enabling oral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional peptides are used to inhibit flavivirus entry, then virus-to-cell fusion is blocked, but the peptides are degraded by peptidases, limiting administration routes
Solution Approach 1:
The patent applies retro-inverso peptide technology, which inverts the conventional L-amino acid configuration to D-amino acids. This inversion makes the peptide resistant to peptidase degradation while maintaining binding affinity to the flavivirus E protein, thereby enabling oral administration
2Reliability
If L-amino acid peptides are used, then binding affinity to flavivirus E protein is achieved, but susceptibility to peptidase degradation occurs
Solution Approach 1:
The patent synthesizes retro-inverso peptides using D-amino acids instead of conventional L-amino acids. This configuration inversion provides peptidase resistance while maintaining the ability to bind to the flavivirus E protein, resolving the contradiction between stability and manufacturability
3Ease of operation
If non-oral administration routes are used, then peptide efficacy is maintained, but treatment accessibility is reduced in areas with limited medical access
Solution Approach 1:
By inverting the amino acid configuration to D-forms, the patent enables oral bioavailability of the antiviral peptide. This allows treatment to be administered via simple oral routes rather than requiring injectable or intravenous methods, significantly improving accessibility in resource-limited settings
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 peptides effectively block flavivirus entry into host cells and are stable enough for oral administration, potentially increasing treatment accessibility and reducing infection rates by providing a broad-spectrum therapeutic option for flaviviral infections.
Implementation Method 1
provides and includes a sequence of residues capable of aligning and binding with specific ligands present and located upon regions of a flavivirus virion's class II E protein
Implementation Method 2
identifies enantiopure isomers comprising peptides highly resistant to degradation by various naturally-occurring proteases
Data Source
AI summary
The invention pertains to inhibitors bindable to regions of a virus. More particularly, the invention relates to inhibitors bindable to regions of flaviviral envelope glycoprotein, or flaviviral virus E protein, a class II viral E protein. Even more particularly, the invention relates to peptides inhibitory to virus-to-cell fusion and virus entry into animal cells. The invention also contains methods of determining said inhibitors, bindable to regions of the flaviviral E protein complex, (e.g., those of dengue and zika viruses) as candidates for in vivo anti-viral compounds that are also resistant to degradation by peptidases and thus extraordinarily suitable for oral, in addition to other, routes of administration.