Fig. 7: Devising combination treatment in MaugOs against enteric viral infections. | Nature Communications

Fig. 7: Devising combination treatment in MaugOs against enteric viral infections.

From: Macrophage-augmented intestinal organoids model virus-host interactions in enteric viral diseases and facilitate therapeutic development

Fig. 7: Devising combination treatment in MaugOs against enteric viral infections.

a Profiling the effect of a group of clinically used immunosuppressants on the expression of IL-1β and viral RNA in OC43-infected MaugOs at 36 hours post-treatment (n = 2). 6-TG: 6-Thioguanine; 6-MP: 6-mercaptopurine; CsA: Cyclosporin A; MTX: Methotrexate; Tof: Tofacitinib; AZA: Azathioprine; 5-ASA: 5-aminosalicylic acid; Pred: Prednisolone; Dex: Dexamethasone; Bud: Budesonide. b IL-1β RNA expression in OC43-infected MaugOs following 36-hours treatment of budesonide, dexamethasone, and prednisolone, respectively, (n = 4). c OC43 viral RNA level in MaugOs treated with 1 μM nirmatrelvir (Nir) for 36 hours (n = 4). d The effect of nirmatrelvir, budesonide and MCC950 (NLRP3 inhibitor) on the protein level of pro IL-1β and NF-κB at 36 hours post-treatment in OC43-infected MaugOs. e–f QRT-PCR quantification of OC43 viral RNA and IL-1β gene expression (e), and ELISA quantification of IL-1β production (f) in MaugOs following 36-hours combination treatment with 1 μM nirmatrelvir and 1 μM budesonide (n = 4). g PCA analysis of different MaugOs groups (n = 3). Control: uninfected MaugOs; OC43: OC43-infected MaugOs; OC43+Nir: 1 μM nirmatrelvir treatment in OC43-infected MaugOs; OC43+Acetate: 50 mM acetate treatment in OC43-infected MaugOs; OC43+Nir+Acetate: combination treatment of 1 μM nirmatrelvir and 50 mM acetate in OC43-infected MaugOs. h–i OC43 viral RNA level (h), IL-1β gene expression and protein production (I) in MaugOs following 36-hours combination treatment with 1 μM nirmatrelvir and 50 mM acetate (ace) (n = 4). j The percentages of mapped OC43 viral transcripts in different groups of MaugOs (n = 3). k Whole genome view of mapped transcripts by RNA-seq across the OC43 genome in different groups of MaugOs (n = 3). l Top 20 significantly regulated KEGG pathways in OC43-infected MaugOs upon combination treatment of nirmatrelvir and acetate, compared to nirmatrelvir treatment alone (n = 3). All data were presented as means of biological replicates ± SEM. Panel b, c, e, f, h and i use Mann–Whitney test with two tailed; J uses One-way ANOVA followed by Dunn’s multiple comparison test (two-sided). *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.

Back to article page