Trimeric Antiviral Peptides for Broad SARS-CoV-2 Spike Binding
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Solution Overview
Problem
There is a need for effective methods and compositions to prevent or stop the spread of SARS-CoV-2, which has caused significant economic and social losses, and existing solutions are inadequate.
Innovation Solution
Development of peptides comprising collagen trimerizing domains bound to viral protein binding domains through chemical linkers, forming peptide complexes that can be administered to treat viral diseases by targeting viral proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional antiviral therapies are used, then viral infection can be inhibited to some extent, but they lack broad spectrum effectiveness against multiple SARS-CoV-2 variants and have limited therapeutic potential
Solution Approach 1:
The peptide is designed with a collagen trimerizing domain that can bind to the spike protein of multiple SARS-CoV-2 variants (Wuhan-Hu-1, Delta, Omicron) through a conserved binding interface. This universal binding capability allows a single peptide sequence to effectively inhibit multiple viral strains, achieving broad spectrum effectiveness without requiring variant-specific therapies.
Solution Approach 2:
The therapeutic composition combines the peptide with a collagen trimerizing domain and a chemical linker to form a composite molecular structure. This composite design enables the peptide to leverage the trimerization capability of collagen domains while maintaining specific viral protein binding activity, thereby enhancing both binding affinity and therapeutic effectiveness across multiple variants.
2Reliability
If peptide complexes are developed to target viral proteins, then therapeutic effectiveness can be improved, but the complexity of the molecular structure increases
Solution Approach 1:
The peptide is divided into distinct functional segments: a collagen trimerizing domain responsible for forming trimeric structures, a chemical linker providing flexibility and connectivity, and a viral protein binding domain responsible for specific viral target engagement. This segmentation allows each domain to be optimized independently while maintaining overall functional integrity, reducing the complexity burden of the complete molecular structure.
Solution Approach 2:
The chemical linker acts as an intermediary element between the collagen trimerizing domain and the viral protein binding domain. This linker provides necessary flexibility and spatial arrangement, allowing the two functional domains to operate independently while maintaining their cooperative effect, thereby simplifying the overall molecular design and reducing structural complexity.
3Strength
If a collagen trimerizing domain is used to bind viral proteins, then binding affinity can be enhanced, but the peptide may trigger immune responses against collagen structures
Solution Approach 1:
The peptide employs a localized collagen trimerizing domain that is structurally distinct from native collagen molecules. The domain is designed to form trimers with specific geometric constraints that mimic but do not fully replicate natural collagen structures. This local quality differentiation allows the peptide to achieve strong binding affinity through trimerization while minimizing recognition by the immune system, as the trimerizing domain is not identical to endogenous collagen epitopes.
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 peptide complexes effectively inhibit viral infection by binding to viral proteins, demonstrating potent inhibition of SARS-CoV-2 strains including Wuhan-Hu-1, Delta, and Omicron, and provide a therapeutic approach to treat viral diseases.
Implementation Method 1
The first collagen trimerizing domain, the second collagen trimerizing domain and the third collagen trimerizing domain are covalently bound together thereby binding the first peptide, the second peptide and the third peptide together
Data Source
AI summary
Provided herein are, inter alia, peptides capable of binding viral proteins and thereby preventing viral infection, replication and spread (e.g., SARS CoV-2). The conjugates provided herein include a trimerizing domain (e.g., a collagen 18 trimerizing domain) attached through a peptide linker to a viral protein binding domain (e.g., a spike binding domain). The peptides and trimeric compositions provided herein exhibit a unique trimeric symmetry which results in superior binding affinities and low binding entropies providing for desirable compositions inhibit viral entry and treating viral infection.