Mutated SARS-CoV-2 Spike Protein-Encoding Sequences for Receptor Control

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Solution Overview

Problem

Current COVID-19 vaccines based on the SARS-CoV-2 spike protein may interfere with nuclear hormone receptors, leading to potential side effects due to the protein's ability to bind and activate estrogen and androgen receptors, causing unbalanced physiological and pathological activities.

Innovation Solution

Mutate the SARS-CoV-2 spike protein by replacing specific amino acids (Ile or Leu at positions 818, 821, 822, 841, 844, 861, 864, and 865 with Alanine to abolish binding to the NCOA1 domain, maintaining immune response efficacy while reducing receptor activation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the wild type SARS-CoV-2 spike protein is used in vaccines, then the immune response efficacy is achieved, but the protein binds to nuclear hormone receptors causing potential side effects

Engineering Contradiction:

Improveimmune response efficacyVSAvoidreceptor binding side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by mutating specific amino acid residues (Ile/Leu at positions 818, 821, 822, 841, 844, 861, 864, and 865) in the spike protein sequence. These parameter changes at the molecular level abolish the protein's ability to bind to nuclear hormone receptors while preserving its immunogenicity, thereby resolving the contradiction between efficacy and safety

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies local quality by making targeted mutations only at specific positions (818, 821, 822, 841, 844, 861, 864, and 865) within the spike protein sequence rather than altering the entire protein. This localized modification eliminates harmful receptor binding while maintaining the overall structure and immunogenic properties of the spike protein

Inventive Principle:

Principle #3Local quality

2Object-affected harmful factors

If the spike protein is modified to reduce receptor binding, then safety is improved, but immune response efficacy may be compromised

Engineering Contradiction:

Improvereceptor binding side effectsVSAvoidimmune response efficacy

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent carefully selects and applies parameter changes (amino acid substitutions) that specifically affect receptor binding parameters while leaving immunogenic parameters unchanged. The mutations at positions 818, 821, 822, 841, 844, 861, 864, and 865 are chosen to abolish nuclear hormone receptor binding without compromising the protein's ability to elicit protective immune responses

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the harmful property of the spike protein (its ability to bind nuclear hormone receptors) into a beneficial design feature by identifying and mutating the specific residues responsible for this binding. This allows the creation of a modified protein that eliminates the harmful effect while preserving the beneficial immunogenic effect

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20250282831A1Novel protein and nucleic acid sequences for covid-19 vaccines

Publication Date: 2025.09.11 DOMPE FARMACEUTICI SPA

AI summary

The present invention relates to a mutated SARS-COV-2 spike protein, a variant or fragment thereof or an mRNA or DNA encoding them for use in the prevention of COVID-19.