Fig 5. Disrupting the DUB activity of SARS-CoV-2 PLpro does not affect virus replication or disease in K18-hACE2 mice.

K18-hACE2 mice were infected intranasally with 1x10⁴ pfu wild-type or DUB mutant SARS-CoV-2 or mock-infected with DMEM. (A) Survival curves (%). (B) Bodyweight loss (% from initial weight). Dashed line indicates 20% weight loss upon which mice were euthanized. (C) Virus titers in the lungs at 2 or 4 dpi. Virus titers were determined by plaque assay on VeroE6 cells. (D) Viral genomic and subgenomic RNA levels in the lungs at 2 and 4 dpi. Viral RNA levels were determined by RT-qPCR using primers targeting the E (genomic and subgenomic RNA) and RdRp (genomic RNA) coding regions. n = 8 mice per group for the mock; n = 10 mice per group for SARS-CoV-2 wild-type, F69S, and F69R; n = 11 mice per group for SARS-CoV-2 M208S (A-B). n = 6 mice per group (C-D). Data was analyzed using log-rank test (A) and one-way ANOVA with Dunnett’s multiple comparisons test, comparing each group to wild-type SARS-CoV-2 (B-D). ns: not significant, * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001.