ACE2-Binding Fv Antibodies for Variant-Resilient SARS-CoV-2 Blocking
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Solution Overview
Problem
Current approaches to prevent SARS-COV-2 infection by blocking the virus's attachment to the ACE2 receptor in host cells are limited in efficacy and flexibility against viral mutations.
Innovation Solution
Development of Fv-antibodies with specific peptide sequences that bind to the ACE2 receptor, blocking the spike protein's interaction with the receptor, using a high-affinity Fv-antibody library and autodisplay technology on E. coli, and expressing these antibodies as soluble proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional approaches are used to block viral attachment to ACE2 receptor, then prevention of SARS-COV-2 infection is attempted, but efficacy is limited and flexibility against viral mutations is insufficient
Solution Approach 1:
The Fv-antibody is designed to bind to the ACE2 receptor in a manner that provides both high efficacy in blocking viral attachment and broad adaptability against different SARS-COV-2 variants. The antibody's binding mechanism is engineered to be universally effective across multiple viral strains, including future mutations, by targeting conserved regions of the ACE2 receptor that are essential for viral attachment.
Solution Approach 2:
The invention employs specific parameter optimization in the Fv-antibody structure, including engineered amino acid sequences in the complementarity-determining regions (CDRs) that enhance binding affinity to ACE2. By adjusting structural parameters such as antibody concentration, binding kinetics, and structural conformation, the antibody achieves both high preventive efficacy and adaptability to viral variations.
2Measurement precision
If Fv-antibodies are screened from Fv-antibody library using autodisplay technology on E. coli, then high binding affinity to ACE2 receptor is achieved, but complex screening and expression processes are required
Solution Approach 1:
The Fv-antibody library is expressed on the surface of E. coli cells using autodisplay technology, allowing the bacteria to present the antibody fragments themselves during screening. This self-service mechanism enables direct selection of high-affinity binders through binding assays without requiring complex purification or additional expression steps, as the E. coli cells automatically display the Fv-antibodies on their outer membranes for easy screening.
3Reliability
If Fv-antibodies are expressed as soluble proteins, then neutralizing activity against SARS-COV-2 variants is demonstrated, but expression yield and stability must be optimized
Solution Approach 1:
A soluble expression system is employed as an intermediary between the Fv-antibody gene and the final functional protein product. This expression system includes optimized promoters, codon adjustments, and solubility-enhancing tags that mediate the production of stable, soluble Fv-antibody proteins with high neutralizing activity. The expression system acts as a bridge to ensure both high yield and proper folding of the antibody proteins.
Data Source
AI summary
Disclosed are a peptide, an antibody, or an antigen-binding fragment thereof, which specifically binds to an ACE2 (angiotensin-converting enzyme 2) receptor, and a composition for preventing SARS-CoV-2, the composition comprising the same. The peptide includes at least one peptide sequence selected from a group consisting of [SEQ ID NO: 1] GHPVNSVLLDF, [SEQ ID NO: 2] GHPRVNVGGDF, [SEQ ID NO: 3] GVLGPRLLIDY and [SEQ ID NO: 4] DGPINRTTIDY.