Fig. 1.

Macrocyclic peptide selection strategy and selection results. (A) Enrichment of library recovery across rounds for two random 15-mer peptide libraries initiated with chloroacetyl-d-tyrosine and -l-tyrosine. Rounds with fetal calf serum added during incubation are marked as “serum”. (B) Dose–response curves from screening of peptides identified by high throughput sequencing of enriched libraries for inhibition of pseudovirus infection in VeroE6 cells. (C) ELISA showing lack of competition for ACE2 binding to spike protein by the most promising peptide hits, compared to REGN_10933 antibody positive control. (D) Dose–response curve for SARS-CoV-2 inhibition assays in HEK293 ACE2+ TMPRSS2+ cells with the most promising hits from the pseudovirus screen. (E) Structure of most promising hit, peptide S1b3inL1, and its sequence. Error bars are SD of technical triplicates (duplicate for ELISA), with a representative shown of duplicate experiments.