Fig. 4. Therapeutically administered nanobody rescues mice from lethal SARS-CoV-2 infection.

a Timeline of the challenge experiment. K18-hACE2 transgenic mice were challenged with 86 PFU of SARS-CoV-2 (blue, ‘wild-type’) or 100 PFU of the beta variant (red) and injected with Fu2-Alb1 (half-life extended Fu2) at indicated timepoints. b Weight of mice during the challenge experiment. The mean weight of each mouse of day 0 to day 2 served as baseline and the weight loss relative this baseline is shown. Uninfected mice (n = 18) are shown in gray, untreated infected mice (n = 15) in black. Half of the untreated mice are historical controls from identical, previously conducted experiments. The weight for the same unchallenged control mice is shown in the upper and lower panel. c Weight loss for day 5 for each group. Fu2-Alb1-treated mice (n = 4 animals) experienced significantly reduced weight loss compared to untreated mice (n = 7 animals) following infection with wild-type virus (p = 0.002; Mann–Whitney U = 0, one-tailed). Significant protection against weight loss was similarly evident in Fu2-Alb1 treated mice (n = 4 animals) compared to untreated mice (n = 8 animals) following infection with the beta variant (p = 0.003; Mann–Whitney U = 0, one-tailed). d Analysis of viral load in oropharyngeal samples from mice at day 5 in infected groups. Following infection with wild-type virus, Fu2-Alb1-treated mice (n = 4 animals) had significantly reduced viral loads compared to untreated mice (n = 7 animals), evident for both E-gene and subgenomic E transcripts expressed as a ratio of copies to copies of ABL1 (p = 0.0143, Mann–Whitney U = 0, one-tailed). Statistical comparisons are summarized as: *p ≤ 0.05; **p ≤ 0.01; ****p ≤ 0.0001; ns not significant. Groups displaying significant weight loss compared to uninfected mice are annotated above the points for that group. Exact P-values are provided in Table S3. No adjustments were made for multiple comparisons. Source data are provided as a Source Data file for b and d.