Fig. 2: Caspase-6 inhibition attenuates MERS-CoV replication in human lung tissues and human intestinal organoids, and improves the survival of hDPP4-KI mice.

a,b, Ex vivo human lung tissues were infected with MERS-CoV and treated with z-VEID-fmk. Tissues and supernatants were collected at 24 hpi for immunostaining (a) and RT–qPCR (b; n = 8). c–f Human intestinal organoids were infected with MERS-CoV and treated with z-VEID-fmk. c, Organoids were fixed at 24 hpi for immunostaining to detect N protein expression. d, Infected cells were quantified by counting the percentage of cells exhibiting N protein expression in each organoid (n = 5). e, N gene expression was quantified by RT–qPCR (n = 3). f, Infectious titre was determined by plaque assay (n = 6). The limit of detection (LOD) was 50 plaque-forming units (PFU) per ml. g, hDPP4-KI mice were inoculated intranasally with 2.5 × 10³ PFU MERS-CoV_MA followed by intraperitoneal administration of DMSO or 12.5 mg kg⁻¹ day⁻¹ z-VEID-fmk for 6 days or until sample collection. h, A subset of mice were collected at 2 and 4 dpi. Mouse lungs were immunolabelled to detect MERS-CoV N expression. The experiment was repeated three times independently with similar results. i, Viral gene expression in mouse lungs was quantified by RT–qPCR (n = 6). j, Infectious titre was determined by plaque assay (n = 6). The LOD was 50 PFU ml⁻¹. k, The expression of genes encoding pro-inflammatory cytokines and chemokines was quantified by RT–qPCR (n = 6 for the two infected groups, n = 3 for the mock-infected group). l,m, The body weight (l) and survival (m) of infected mice was monitored for 14 days (n = 10 for z-VEID-fmk group, n = 9 for DMSO group). m, The fraction of survivors is shown. Data are mean ± s.d. from the indicated number of biological repeats. One-way ANOVA (k), two-way ANOVA (e,l), two-sided Student’s t-test (b,d,f,i,j) or log-rank (Mantel–Cox) test (m). Scale bars: 50 μm (a), 20 μm (c) and 100 μm (h).

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