Engineering a "muco-trapping" ACE2-immunoglobulin hybrid with picomolar affinity as an inhaled, pan-variant immunotherapy for COVID-19.

ABSTRACT: Soluble angiotensin-converting enzyme 2 (ACE2) can act as a decoy molecule that neutralizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by blocking spike (S) proteins on virions from binding ACE2 on host cells. Based on structural insights of ACE2 and S proteins, we designed a "muco-trapping" ACE2-Fc conjugate, termed ACE2-(G₄S)₆-Fc, comprised of the extracellular segment of ACE2 (lacking the C-terminal collectrin domain) that is linked to mucin-binding IgG1-Fc via an extended glycine-serine flexible linker. ACE2-(G₄S)₆-Fc exhibits substantially greater binding affinity and neutralization potency than conventional full length ACE2-Fc decoys or similar truncated ACE2-Fc decoys without flexible linkers, possessing picomolar binding

SUBMITTER: Tiruthani K 

PROVIDER: S-EPMC11256170 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature