A Piecewise Design Approach to Engineering a Miniature ACE2 Mimic to Bind SARS-CoV-2

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.

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Work Title A Piecewise Design Approach to Engineering a Miniature ACE2 Mimic to Bind SARS-CoV-2
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Creators
  1. Yashavantha L. Vishweshwaraiah
  2. Brianna Hnath
  3. Jian Wang
  4. Morgan Chandler
  5. Arnab Mukherjee
  6. Neela H. Yennawar
  7. Squire J. Booker
  8. Kirill A. Afonin
  9. Nikolay V. Dokholyan
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. ACS Applied Bio Materials
Publication Date May 20, 2024
Publisher Identifier (DOI)
  1. https://doi.org/10.1021/acsabm.4c00222
Deposited November 18, 2024

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Version 1
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  • Created
  • Added papers_pdf_vhwcmybad_acsabm_24.pdf
  • Added Creator Yashavantha L. Vishweshwaraiah
  • Added Creator Brianna Hnath
  • Added Creator Jian Wang
  • Added Creator Morgan Chandler
  • Added Creator Arnab Mukherjee
  • Added Creator Neela H. Yennawar
  • Added Creator Squire J. Booker
  • Added Creator Kirill A. Afonin
  • Added Creator Nikolay V. Dokholyan
  • Published
  • Updated