%0 Journal Article
%T Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalization.
%A Morgan DC
%A Morris C
%A Mahindra A
%A Blair CM
%A Tejeda G
%A Herbert I
%A Turnbull ML
%A Lieber G
%A Willett BJ
%A Logan N
%A Smith B
%A Tobin AB
%A Bhella D
%A Baillie G
%A Jamieson AG
%J Pept Sci (Hoboken)
%V 113
%N 4
%D Jul 2021 8
%M 33615115
%F 2.592
%R 10.1002/pep2.24217
%X COVID-19 is caused by a novel coronavirus called severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Virus cell entry is mediated through a protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (ACE2). A series of stapled peptide ACE2 peptidomimetics based on the ACE2 interaction motif were designed to bind the coronavirus S-protein RBD and inhibit binding to the human ACE2 receptor. The peptidomimetics were assessed for antiviral activity in an array of assays including a neutralization pseudovirus assay, immunofluorescence (IF) assay and in-vitro fluorescence polarization (FP) assay. However, none of the peptidomimetics showed activity in these assays, suggesting that an enhanced binding interface is required to outcompete ACE2 for S-protein RBD binding and prevent virus internalization.