Fig. 1: Fusion inhibitory lipopeptides block SARS-CoV-2-Spike-mediated fusion in hACE2-transfected cells and SARS-CoV-2 replication in vitro and ex vivo. | Communications Biology

Fig. 1: Fusion inhibitory lipopeptides block SARS-CoV-2-Spike-mediated fusion in hACE2-transfected cells and SARS-CoV-2 replication in vitro and ex vivo.

From: Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity

Fig. 1

a Schematic of SARS-CoV-2 Spike protein primary structure with peptide sequence. NTD N-terminal domain, RBD receptor-binding domain, SD1 subdomain-1, SD2 subdomain-2, FP fusion protein, HRN heptad repeat N-terminal, CD connector domain, HRC heptad repeat C-terminal, TM transmembrane domain, CT cytoplasmic tail. b Schematic presentation of the composition of the monomer-PEG24 (SARSHRC-PEG24-chol) and dimer-PEG4 ([SARSHRC-PEG4]2-chol) peptides. c Cell–cell fusion inhibition assay in 293T-ACE2 cells with 293T-Spike Wuhan D614. Data are means ± standard deviation (SD) (error bars) from three separate experiments with the curve representing a four-parameter dose–response model (Ctrl HRC4: control peptide, measles-specific). d Virus inhibition assay, measuring peptide-mediated inhibition of SARS-CoV-2 (Wuhan D614) infection (100 plaque-forming unit- PFU/well) in Vero cells. Percent inhibition was calculated as the ratio of PFU in the presence of a specific concentration of inhibitor and the PFU in the absence of inhibitor. Data are means ± SD from three separate experiments. e Inhibition of infection in organotypic cultures from lungs of K18-hACE2 mice with either recombinant SARS-CoV-2 neon-green or SARS-CoV-2 Delta (500 PFUs), with peptides added into the culture during 96 h, assessed using RT-qPCR (4–8 slices per condition, generated from 3 mice, results presented as mean ± SD). f Spread of fluorescent rSARS-CoV-2 neon-green virus in representative fluorescence micrographs of lung organotypic cultures, in the presence and absence of peptide (arrows indicate the sites of viral replication in cultures, (scale bars: 1 mm). g Quantification of the percentage of infected area, detected by immunofluorescence on scanned slides using QuPath, Open-source software for digital pathology image analysis, results presented as mean ± SD (*p < 0.05, **p < 0.01, ***p < 0.001, Mann–Whitney test).

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