Peptide-Nucleic Acid Hybrid Composition for Variant RBD Neutralization
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Solution Overview
Problem
Existing antiviral strategies struggle to effectively neutralize SARS-CoV-2 variants due to escape mutations that reduce the binding affinity of affinity reagents, leading to increased viral resistance and reduced efficacy.
Innovation Solution
Development of a hotspot-derived peptide-nucleic acid hybrid molecule that synergistically interacts with the receptor binding domain (RBD) of SARS-CoV-2, utilizing a novel in vitro evolutionary technique to enhance binding affinity and stability, even in the presence of mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If affinity reagents are used to block virus-host cell interactions, then viral infection can be prevented, but escape mutations reduce binding affinity and neutralization efficacy
Solution Approach 1:
The patent combines a hotspot-derived peptide (mimicking the hACE2 receptor binding interface) with a nucleic acid aptamer into a single hybrid molecule. The peptide component specifically targets the RBD hotspot region, while the nucleic acid aptamer provides structural stability and enhances binding affinity, creating a synergistic effect that maintains efficacy against multiple variants
Solution Approach 2:
The invention uses a composite structure consisting of amino acid-based peptide and nucleic acid-based aptamer components. This composite hybrid molecule leverages the complementary strengths of both materials: the peptide's specificity for the RBD hotspot and the nucleic acid's structural stability and high affinity binding capabilities
2Adaptability or versatility
If antibody cocktails are administered to counteract variants, then immune evasion can be addressed, but viral resistance increases and binding interaction with host cell receptor strengthens
Solution Approach 1:
The hotspot-derived peptide in the hybrid molecule copies the critical binding interface of the hACE2 receptor that naturally interacts with the viral RBD. By mimicking this essential host cell binding site, the peptide can competitively inhibit viral attachment without relying on antibodies that may be evaded by mutations
3Reliability
If non-competitive affinity reagents are co-administered to address variants, then neutralization can be enhanced, but complexity of treatment increases
Solution Approach 1:
The patent merges the peptide and aptamer components into a single hybrid molecule that functions as one therapeutic agent, eliminating the need for co-administration of multiple reagents while maintaining enhanced neutralization efficacy against variants
Data Source
AI summary
The present disclosure relates to a composition for preventing or treating coronavirus infection, including a hotspot-derived peptide-nucleic acid hybrid molecule. It was confirmed that in vitro evolution-based hotspot-derived peptide-nucleic acid hybrid molecule prepared using the method of the present invention has high binding affinity for the RBDs of SARS-COV-2 VOCs (alpha, beta, gamma, delta, and omicron). In particular, it was found that the greatest binding tolerance was exhibited in the most highly mutated omicron. Furthermore, the hybrid molecule showed high RBD binding affinity in competition with RBD-binding nucleic acid aptamers, macrocyclic peptides, and monoclonal antibodies. The hybrid molecule also exhibited excellent nuclease resistance and serum stability, indicating potential as virus neutralizer in addition to SARS-COV-2.