Pheromonicin Colicin Fusions Target Conserved SARS-CoV-2 Proteins
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Solution Overview
Problem
Current drugs against SARS-CoV-2 have limited efficacy against mutated strains, require time to produce antibodies, and fail to address infected host cells and inflammatory cytokine storms.
Innovation Solution
Development of pheromonicins, which are fusion proteins combining channel-forming E1 family colicins with antibody mimetics targeting the conserved E and M proteins of SARS-CoV-2, providing immediate antiviral activity and broad-spectrum protection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemical drugs are used to screen against SARS-COV-2, then antiviral activity is achieved, but the virus develops resistance rapidly due to high mutation probability
Solution Approach 1:
The patent changes the target parameter from the highly variable S protein to the conserved E and M proteins, which have low mutation rates. This parameter change in target selection enables the drug to maintain effective antiviral activity against mutated strains, resolving the contradiction between antiviral activity and resistance development
Solution Approach 2:
The patent creates a composite therapeutic agent by fusing colicin Ia (a bacteriocin with membrane-piercing capability) with antibody mimetics targeting viral proteins. This composite structure combines the killing function of colicin with the specificity of antibody binding, achieving broad-spectrum antiviral activity against epidemic and mutant strains
2Reliability
If vaccines are used to produce antibodies against SARS-COV-2, then immunity is achieved, but it takes several tens of days for antibodies to be produced
Solution Approach 1:
The patent extracts and utilizes the pre-formed colicin Ia protein, which already possesses membrane-piercing and killing capabilities, rather than relying on the host to produce antibodies through vaccination. This extraction of ready-to-act therapeutic molecules eliminates the time delay associated with antibody production
Solution Approach 2:
The patent employs antibody mimetics that copy the binding function of antibodies without requiring the host immune system to produce them. These mimetics directly bind to viral proteins and trigger colicin-mediated killing, achieving immediate effect without the time lag of natural antibody production
3Reliability
If drugs targeting the S protein are used, then antiviral effect is achieved, but efficacy is lost when virus mutations occur
Solution Approach 1:
The patent fundamentally changes the target parameter from the mutable S protein to the conserved E and M proteins. These target proteins maintain stable structures across virus variants, enabling the drug to effectively target and kill both epidemic and mutant strains, thus resolving the efficacy loss problem
4Reliability
If existing drugs are used against SARS-COV-2, then viral killing is achieved, but infected host cells and inflammatory cytokine storms are not addressed
Solution Approach 1:
The patent endows the therapeutic agent with multi-functionality by combining colicin Ia (which kills both virus and infected cells) with antibody mimetics. This universal agent simultaneously achieves viral killing, eliminates infected host cells, and can modulate inflammatory responses, addressing multiple pathogenic effects of SARS-COV-2 infection
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
Pheromonicins effectively kill SARS-CoV-2 and infected host cells, reduce pulmonary lesions, and alleviate inflammatory cytokine storms, offering immediate protection against both epidemic and mutant strains.
Implementation Method 1
the channel-forming domain can form a voltage-activated ion channel in the bacterial cell membrane (lipid bilayer)... The channel will open when sensing a transmembrane potential of −50 mv. Due to the large pore size (approximately 9-11 Å) of the channel, almost all ions can leak out through the huge aqueous pore
Implementation Method 2
The antibody mimetics are selected from two types of 28-residues, with amino acid sequences of SEQ ID NO. 1 and SEQ ID NO. 2... The antibody mimetics are constructed using the antibody sequences of the disclosed E protein and M protein of SARS-COV-2 as blueprints, and can recognize the E protein and M protein of SARS-COV-2
Implementation Method 3
Driven by hydrophilic and hydrophobic forces, the channel-forming domain can insert into the inner membrane (cell membrane) of E. coli to form an ion channel without consuming energy
Data Source
AI summary
A pheromonicin against SARS-COV-2. Antibody mimetics, i.e., two 28-residues are designed for the first time by selecting the E protein and M protein of SARS-COV-2, which are relatively conserved and have low probability of mutation, as targets. Pharmacodynamic experiments performed using three SARS-COV-2 strains (the epidemic strain GD108, the South Africa strain SA and the India strain IND) respectively prove that fusion proteins obtained by linking the 28-residues to colicin can provide effective protective efficacy against pulmonary lesions induced by SARS-COV-2, and can be used as drugs for treating and preventing SARS-COV-2.