Short Synthetic Peptides for Blocking EV-A71 Replication

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

There is no approved therapeutic drug to combat Enterovirus A71 (EV-A71) infections, which cause severe central nervous system complications and result in significant morbidity and mortality, particularly in children.

Innovation Solution

Development of short synthetic peptides, such as PKKRRQRRRAYSRAX1X2X3QLX4S, that inhibit Hsp27 phosphorylation and hnRNP A1 redistribution, thereby suppressing EV-A71 replication and propagation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If short synthetic peptides are developed to inhibit Hsp27 phosphorylation and hnRNP A1 redistribution, then antiviral activity against EV-A71 is improved, but the complexity of drug development increases

Engineering Contradiction:

Improveantiviral activityVSAvoiddrug development complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The invention segments the complex viral replication process into specific molecular targets (Hsp27 phosphorylation site, hnRNP A1 translocation pathway) and designs peptides that specifically interfere with these segmented steps, thereby achieving antiviral activity through targeted inhibition rather than broad-spectrum action

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The synthetic peptides act as intermediary molecules that mediate the inhibition between the cellular machinery and viral replication processes. The peptides bind to Hsp27 and prevent its phosphorylation, thereby indirectly blocking viral protein translation and genome replication without directly targeting viral components

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If short synthetic peptides are used to suppress EV-A71 replication, then therapeutic efficacy is improved, but the ease of manufacture decreases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidpeptide production ease

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The invention employs short synthetic peptides (15-20 amino acids) that can be produced through chemical synthesis rather than requiring complex biological manufacturing systems. These short peptides are designed to be sufficiently stable for therapeutic use while maintaining ease of synthesis through standard peptide chemistry methods

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention optimizes peptide parameters including length (15-20 amino acids), amino acid composition, and terminal modifications to achieve the optimal balance between stability, activity, and manufacturability. Specific amino acid sequences are selected to enhance peptide stability while maintaining synthetic accessibility

Inventive Principle:

Principle #35Parameter changes

3Productivity

If Hsp27 phosphorylation is inhibited to block viral replication, then viral protein translation is reduced, but the duration of action of the peptide may be limited

Engineering Contradiction:

Improveviral replication suppressionVSAvoidpeptide action duration

Core Design Contradiction:

ProductivityVSDuration of action of moving object

Solution Approach 1:

The peptides are designed to act preliminarily by blocking Hsp27 phosphorylation before viral replication can proceed. By preventing the phosphorylation event that triggers hnRNP A1 translocation and subsequent viral protein translation, the peptides establish a preventive barrier that stops viral replication at an early stage

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention aims to achieve continuous antiviral action through sustained peptide presence that continuously blocks Hsp27 phosphorylation. The peptide design incorporates features that enhance stability and persistence in the cellular environment, ensuring continuous inhibition of the phosphorylation pathway throughout the viral replication cycle

Inventive Principle:

Principle #20Continuity of useful action

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 inhibit EV-A71 replication and propagation, offering a potential therapeutic approach by reducing viral protein translation and genome RNA replication.

Implementation Method 1

Hsp27 can be modulated by phosphorylation at serine 15, 78, and 82 in response to a variety of signals

Methodology Applied

Scientific EffectPhosphorylation:

Implementation Method 2

the inventors unexpectedly identify short synthetic peptides that may suppress Hsp27 phosphorylation and hnRNP A1 redistribution triggered by EV-A71 infection

Methodology Applied

Scientific EffectProtein phosphorylation inhibition:

Data Source

PatentUS20250368687A1Short synthetic peptides and uses thereof in the treatment of enterovirus infection

Publication Date: 2025.12.04 CITY UNIVERSITY OF HONG KONG

AI summary

Disclosed herein are synthetic peptides and compositions comprising the same for the treatment of enterovirus infection. Also disclosed herein are methods of treating enterovirus infection by administering to a subject in need of such treatment a composition containing an effective amount of a synthetic peptide of the present disclosure. In some cases, the subject is a human.