The spike mutation, Y453F, enhances replication and morbidity in ferrets
(A) Deep sequencing of RBD mutations of SARS-CoV-2 from ferret passage 2 swab (see Figure 1A) before and after isolation in Vero cells.
(B–E) RNA (B) and infectious virus (C) shedding dynamics of ferrets directly infected with either WT (orange circles; as previously described in Peacock et al. [2021a]) or Y453F (i.e., ferret passage 2; black and white squares) SARS-CoV-2. n = 4 naive ferrets in each group were infected with 105 p.f.u. of either virus. Percentage weight loss (D) and change in body temperature (E) were recorded daily. Data plotted as mean ± s.d. Statistics on (B) and (C) determined by multiple Mann-Whitney tests. ∗0.05 ≥ P.
(F and G) Spike RBD (F) and non-RBD (G) mutations seen in Vero-grown ferret passage 2 virus (time 0) from Figures 2A–2D and dynamics over time in directly infected ferrets. Hash sign marks samples with insufficient coverage to determine sequence proportions.