Fig. 1: Characterization of CIPS and its anti-SARS-CoV-2 capacity in vitro.

a, TEM image of exfoliated a CIPS NS. b,c, AFM image (b) and measurement (c) of CIPS NSs, showing the thickness (colour code bar) and size (green line, 280 nm) distribution (c represents the thickness of the area, depicted by the green line in b). d, Coordination structure of Cu with S atoms in CIPS, determined by EXAFS. e, Schematic illustration of the CIPS crystal structure from the top (y–x), lateral (z–y) and front (z–x) sides. f, Schematic representation of the CIPS capacity to inhibit SARS-CoV-2 infection of target cells. g, Anti-SARS-CoV-2 effect and cytotoxicity of CIPS towards Vero-E6 cells in vitro. IC₅₀, 50% inhibitory/cytotoxic concentration (pM); EC₅₀, 50% effective/antiviral concentration (pM); SI, ratio between IS₅₀ and EC₅₀. Mean ± s.e.m. of n = 3–5 biological replicates. h, Phase-contrast images of Vero-E6 cells 48 h post-infection with SARS-CoV-2 in the absence or presence of CIPS. The numbers at the bottom of the images represent the percentage of the cell culture surface covered by cells, which correlates with cell survival. Scale bars, 50 μm. i, Antiviral effect of post-infection treatment of Vero-E6 cells with CIPS. Cells were infected with SARS-CoV-2 for 2 h and then treated with CIPS. The intracellular SARS-CoV-2 was evaluated after 48 h. Mean ± s.e.m. of n = 3 biological replicates. j, Therapeutic antiviral effect of CIPS against SARS-CoV-2. Vero-E6 cells were infected with SARS-CoV-2, and CIPS was added at various times after virus infection. Mature SARS-CoV-2 released into the medium was measured after 48 h. Mean ± s.e.m. of n = 5 biological replicates. k–n, Anti-SARS-CoV-2 capacity of CIPS in human airway epithelial organoids: SARS-CoV-2 replication was evaluated in organoids infected with the virus in the absence or presence of CIPS (k), images of haematoxylin and eosin (H&E) staining of cultured tissue cross-sections (l), confocal microscopy images of human airway epithelial organoids after SARS-CoV-2 infection in the absence or presence of CIPS (the white arrows indicate tissue damage (m)) and the thickness of human respiratory epithelium sections measured by ImageJ (n). Scale bars, 20 μm. Blank, uninfected tissue; virus, tissue infected with SARS-CoV-2; virus + CIPS, tissue infected with SARS-CoV-2 and treated with CIPS. DAPI, 4,6-diamidino-2-phenylindole. For the data in k, the mean ± s.e.m. of n = 3 biological replicates is presented; for the data in n, the mean ± s.e.m. of n = 3 technical replicates from a representative experiment out of two performed is shown. In i,j,k and n, the statistical significance was calculated by one-way analysis of variance (ANOVA) with Tukey’s multiple comparisons test. Open circles represent the individual replicate values.

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