{Reference Type}: Journal Article
{Title}: Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalization.
{Author}: Morgan DC;Morris C;Mahindra A;Blair CM;Tejeda G;Herbert I;Turnbull ML;Lieber G;Willett BJ;Logan N;Smith B;Tobin AB;Bhella D;Baillie G;Jamieson AG;
{Journal}: Pept Sci (Hoboken)
{Volume}: 113
{Issue}: 4
{Year}: Jul 2021 8
{Factor}: 2.592
{DOI}: 10.1002/pep2.24217
{Abstract}: 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.