Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics

We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 μM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.