Figure 1: Peptide-lipid conjugates that inhibit SARS-CoV-2 spike (S)-mediated fusion.
(A) The functional domains of SARS-CoV-2 S protein: receptor-binding domain (RBD) and heptad repeats (HRN and HRC) are indicated. (B) Sequence of the peptides that derive from the HRC domain of SARS-CoV-2 S. (C) Monomeric and dimeric forms of lipid tagged SARS-CoV-2 inhibitory peptides that were assessed in cell-cell fusion assays. (D) Cell-cell fusion assays with different inhibitory peptides. The percentage inhibition is shown for four different peptides used at increasing concentrations. Inhibitory concentrations 50% and 90% were calculated (dotted lines). Percent inhibition was calculated as the ratio of relative luminescence units in the presence of a specific concentration of inhibitor and the relative luminescence units in the absence of inhibitor and corrected for background luminescence. Data are means ± standard deviation (SD) from three separate experiments. The difference between the results for [SARSHRC-PEG4]2-chol and SARSHRC-PEG4-chol lipopeptides are significant (Two-way ANOVA, **** p<0.0001). (E) Fusion inhibitory activity of [SARSHRC-PEG4]2-chol peptide against SARS-CoV-2 S variants, MERS-CoV-2 S, and SARS-CoV S. Data are means ± standard deviation (SD) from three separate experiments.