Protease Biosensor Design for SARS-CoV-2 Detection
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Solution Overview
Problem
Current biosensors for detecting SARS-CoV-2 and protease activity are limited in their ability to specifically identify SARS-CoV-2 replication and inhibit viral transmission, necessitating the development of targeted biosensors for accurate detection and inhibition.
Innovation Solution
The development of protease biosensors encoded with specific nucleotide sequences and degron domains, including a ubiquitin domain and cleavage sites for 3C-like protease, papain-like protease, and caspase, which are packaged in baculovirus vectors, allowing for the detection of protease activity and viral infection in cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If protease biosensors are designed with cleavage sites between reporter proteins for virus detection, then detection capability is improved, but biosensor stability deteriorates due to premature cleavage or degradation
Solution Approach 1:
The biosensor is designed with a degradation-resistant configuration where the reporter proteins are positioned and protected before viral protease activation occurs. The cleavage site is strategically placed and protected until the specific viral protease is activated, preventing premature degradation and ensuring stable biosensor composition until detection is needed.
2Measurement precision
If biosensors are made highly specific to SARS-CoV-2 protease, then detection accuracy is improved, but adaptability to other viruses deteriorates
Solution Approach 1:
The biosensor employs local quality by designing specific cleavage site sequences that are highly specific to SARS-CoV-2 protease at the molecular level, while maintaining overall biosensor architecture that could potentially be adapted to detect other viruses by changing only the specific cleavage site sequence, thus achieving both high specificity and potential adaptability.
3Measurement precision
If biosensor components are placed close together for sensitive FRET detection, then detection sensitivity is improved, but biosensor complexity increases
Solution Approach 1:
The biosensor merges multiple functional elements - reporter proteins, cleavage sites, and degradation-resistant structures - into a single integrated polypeptide chain. This combining of elements achieves sensitive detection through close positioning for FRET while managing complexity through unified structural design rather than separate components.
Data Source
AI summary
The present disclosure provides a biosensor for the detection of protease activity. The detection of protease activity can be used for the detection of viral infection, in particular coronavirus infection. The biosensor described herein can be used to detect SARS-CoV-2. The present disclosure also provides vectors expressing the biosensor and methods for using the same.