SARS-CoV-2 Spike Protein Host Cell Interaction Modulation
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Solution Overview
Problem
Current methods for treating and preventing SARS-CoV-2 infection are limited due to a lack of understanding of host cell receptors and cellular factors mediating virus entry, particularly beyond the angiotensin-converting enzyme 2 (ACE2) pathway, which does not explain the virus's multi-organ tropism and transmissibility.
Innovation Solution
Administering contactin-1 (CNTN1), interleukin 12 receptor subunit beta 1 (IL12RB1), or interleukin 1 receptor accessory protein like 2 (IL1RAPL2) antagonists, such as small molecules, antibodies, or inhibitory nucleic acids, to modulate interactions between the SARS-CoV-2 spike protein and host cell proteins, reducing viral attachment and infection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If only ACE2 pathway is targeted for treatment, then treatment mechanism is simple, but it cannot explain multi-organ tropism and transmissibility
Solution Approach 1:
The patent segments the viral entry process into multiple independent pathways by identifying distinct host factors (ACE2, TMPRSS2, and additional unknown factors) that mediate SARS-CoV-2 entry into different cell types and organs. This segmentation explains multi-organ tropism while maintaining clear, separate treatment targets for each pathway.
Solution Approach 2:
The patent applies universality by identifying host factors that serve multiple functions: ACE2 and TMPRSS2 are involved in both viral entry and normal physiological processes, and additional unknown factors may similarly serve multiple roles. This multi-functionality explains why targeting these factors requires careful consideration of therapeutic windows and side effects.
2Measurement precision
If host cell membrane proteins are studied using current methods, then research is straightforward, but sensitive technologies for studying membrane protein interactomes are lacking
Solution Approach 1:
The patent uses proteomic profiling as an intermediary technology to indirectly study membrane protein interactions. By analyzing the interactome of membrane proteins through proteomic methods, the invention identifies host factors that mediate viral entry without requiring direct observation of the viral-membrane interaction, thus achieving high measurement precision through sophisticated but manageable技术手段.
3Adaptability or versatility
If ACE2 expression patterns are used to predict virus infection, then prediction is simple, but it does not match observed infection patterns in nervous tissue and other organs
Solution Approach 1:
The patent segments the infection prediction model by identifying that different organs and cell types use different host factors for viral entry. Instead of a single ACE2-based prediction model, the invention develops organ-specific predictions based on the presence and expression levels of relevant host factors (ACE2 in respiratory tract, TMPRSS2 in various tissues, and additional factors in nervous tissue), thereby achieving both simplicity and accuracy.
Solution Approach 2:
The patent applies local quality by recognizing that different tissues have different expression patterns of host factors and therefore different susceptibilities to SARS-CoV-2 infection. The invention tailors the prediction model to local tissue characteristics, considering the specific combination of ACE2, TMPRSS2, and other factors present in each organ, which explains why nervous tissue and other organs are affected despite low ACE2 expression.
Data Source
AI summary
Provided herein are methods of treating or preventing SARS-CoV-2 infection comprising modulating interactions between the SARS-CoV-2 spike protein and plasma membrane-expressed host cell proteins, as well as methods of identifying modulators of such interactions.