PPC-Binding Peptides That Block TMPRSS2 Spike Cleavage
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Solution Overview
Problem
Existing approaches to prevent SARS-CoV-2 infection, such as antibodies and small molecules, face challenges due to steric hindrance and limited effectiveness against the PPC region of the spike protein, necessitating a more effective mechanism to block the virus's entry into host cells.
Innovation Solution
Development of Fv-antibodies with high binding affinity to the PPC region of the SARS-CoV-2 spike protein, specifically targeting the peptide sequences SEQ ID NO: 1 (DGRARQSQDDD) and SEQ ID NO: 2 (GSQIALRRRDF), which interfere with the cleavage by TMPRSS2, thereby preventing viral entry.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies are used to bind to the PPC region of spike protein, then binding affinity to the region can be achieved, but steric hindrance from the structure of SP around the PPC region limits the approach and effectiveness
Solution Approach 1:
The patent uses Fv antibody fragments as intermediaries that can access the PPC region more effectively than full antibodies. The Fv fragment's smaller size allows it to navigate the steric hindrance while maintaining binding capability to the target region
Solution Approach 2:
The patent extracts the antigen-binding fragment (Fv) from the complete antibody structure, removing the Fc region that contributes to steric bulk. This extracted Fv fragment retains the ability to bind to the PPC region while overcoming the steric hindrance that limits full antibody access
2Ease of operation
If small molecules are developed as pan-corona drugs to bind to PPC region, then steric hindrance can be overcome, but binding affinity and neutralizing activity may be limited compared to antibodies
Solution Approach 1:
The patent changes the molecular parameters by using Fv fragments with optimized size and structure. This intermediate size - larger than small molecules but smaller than full antibodies - provides both adequate access to the PPC region and sufficient binding affinity for effective neutralization
3Reliability
If Fv-antibodies are developed to bind to PPC region, then both binding affinity and access to the region can be optimized, but the complexity of screening and characterization increases
Solution Approach 1:
The patent employs preliminary screening of Fv libraries against the PPC region to identify high-affinity binders before full characterization. This preliminary selection step reduces the number of candidates requiring extensive testing, thereby managing the overall complexity of the development process
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 Fv-antibodies effectively block the virus's entry into host cells by binding to the PPC region, offering broad protection against various SARS-CoV-2 variants, including Wu-1, Delta, Omicron (BA.2), and Omicron (BA.4/5), with high neutralizing activity and interference with the cleavage process.
Implementation Method 1
The Fv-antibodies effectively block the virus's entry into host cells by binding to the PPC region
Data Source
AI summary
Disclosed are a peptide specifically binding to a PPC region of a SARS-CoV-2 spike protein and a composition for preventing SARS-CoV-2 infection using the same. The peptide includes a peptide sequence of DGRARQSQDDD or GSQIALRRRDE.