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.