Rationally designed, ACE2 mimetic binder to the SARS Cov-2 associated Spike protein for COVID-19 therapeutics and beyond.

ABSTRACT: We have developed a 23 residue, optimized helical peptide biomimetic from the SARS-CoV-2 Spike protein binding partner ACE2 that demonstrated a Therapeutic Index (TI) of > ~ 20 in authentic viral cell challenge assays, including WT and Omicron strains. The therapeutic is an optimized "peptide decoy" based on the virus's human cell target ACE2 and, as such, may have more general applicability across coronavirus family members that use ACE2 for cellular entry. We experimentally verify a comprehensive, rational optimization strategy of the peptide through improved binding, helical content, and solubility from its native sequence. These techniques may have general applicability for helical peptide optimization for other therapeutic targets as well. Importantly, techniques also exist for protec

SUBMITTER: Peters MH 

PROVIDER: S-EPMC12550059 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature