Stabilized SARS-CoV-2 Spike Protein Fusion Mutations
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Solution Overview
Problem
Current vaccines and treatments for COVID-19 lack effectiveness due to the instability and variability of SARS-CoV-2 spike proteins, which complicates the induction of robust and neutralizing antibodies, and there is an urgent need for stabilized pre-fusion SARS-CoV-2 S proteins for improved vaccine design and immune response.
Innovation Solution
Development of recombinant SARS-CoV-2 S proteins with specific mutations and disulfide bridges that enhance thermal stability and trimer yields, maintaining the pre-fusion conformation, and nucleic acid molecules encoding these proteins for use in vaccines and immunization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wild-type SARS-CoV-2 spike protein is used in vaccines, then the vaccine can be produced, but the protein instability and variability reduce antibody induction effectiveness
Solution Approach 1:
The patent introduces specific amino acid mutations (e.g., N501Y, D614G, P681H, L617F) and disulfide bridge formations to alter the structural parameters of the spike protein, thereby enhancing its thermal stability and conformational consistency while maintaining immunogenicity
Solution Approach 2:
The stabilized spike protein is constructed as a composite structure incorporating multiple stabilizing elements (mutations and disulfide bridges) within a single protein molecule, creating a hybrid structure that combines the original viral antigenicity with enhanced structural rigidity
2Stability of the object's composition
If spike protein mutations are introduced to stabilize the protein, then thermal stability and trimer yields improve, but the protein sequence deviates from the wild-type virus
Solution Approach 1:
The patent applies stabilizing mutations and disulfide bridges at specific localized regions of the spike protein (such as the hinge region and subunit interfaces) rather than throughout the entire sequence, thereby improving stability while preserving overall sequence similarity to the wild-type virus
3Reliability
If the spike protein is stabilized in pre-fusion conformation, then antibody neutralization effectiveness increases, but the protein becomes more resistant to conformational changes needed for fusion
Solution Approach 1:
The spike protein is engineered to be pre-stabilized in the pre-fusion conformation before interaction with the host cell, ensuring that the antigen presented to the immune system is in the correct immunogenic state, while the fusion function remains intact for viral entry
Data Source
AI summary
The present invention provides stabilized recombinant pre-fusion SARS COV-2 S proteins, nucleic acids molecules encoding the SARS-COV-2 S proteins and uses thereof.