A Piecewise Design Approach to Engineering a Miniature ACE2 Mimic to Bind SARS-CoV-2.
Yashavantha L VishweshwaraiahBrianna HnathJian WangMorgan ChandlerArnab MukherjeeNeela H YennawarSquire J BookerKirill A AfoninNikolay V DokholyanPublished in: ACS applied bio materials (2024)
As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues its global spread, the exploration of novel therapeutic and diagnostic strategies is still needed. The virus enters host cells by binding the angiotensin-converting enzyme 2 (ACE2) receptor through the spike protein. Here, we develop an engineered, small, stable, and catalytically inactive version of ACE2, termed miniature ACE2 (mACE2), designed to bind the spike protein with high affinity. Employing a magnetic nanoparticle-based assay, we harnessed the strong binding affinity of mACE2 to develop a sensitive and specific platform for the detection or neutralization of SARS-CoV-2. Our findings highlight the potential of engineered mACE2 as a valuable tool in the fight against SARS-CoV-2. The success of developing such a small reagent based on a piecewise molecular design serves as a proof-of-concept approach for the rapid deployment of such agents to diagnose and fight other viral diseases.
Keyphrases
- sars cov
- angiotensin converting enzyme
- respiratory syndrome coronavirus
- angiotensin ii
- binding protein
- high throughput
- loop mediated isothermal amplification
- induced apoptosis
- protein protein
- coronavirus disease
- cell cycle arrest
- dna binding
- small molecule
- cell death
- risk assessment
- climate change
- human health
- transcription factor
- psychometric properties