A Cell-Adapted SARS-CoV-2 Mutant, Showing a Deletion in the Spike Protein Spanning the Furin Cleavage Site, Has Reduced Virulence at the Lung Level in K18-hACE2 Mice.

Here we investigated the virulence properties of a unique cell-adapted SARS-CoV-2 mutant showing a ten-amino acid deletion encompassing the furin cleavage site of the spike protein (Δ680SPRAARSVAS689; Δ680-689-B.1) in comparison to its parental strain (wt-B.1) and two Delta variants (AY.122 and AY.21). After IN inoculation, transgenic K18-hACE2 mice were monitored for 14 days for weight change, lethality, clinical score, and oral swabs were daily collected and tested for the presence of N protein subgenomic RNA. At 3 and 7 dpi mice were also sacrificed and organs collected for molecular, histopathological and immune response profile investigations. The Δ680-689-B.1- infected mice exhibited reduced shedding, lower virulence at the lung level, and milder pulmonary lesions. In the lung, infection with Δ680-689-B.1 was associated with a significant lower expression of some cytokines at 3 dpi (IL-4, IL-27, and IL-28) and 7 dpi (IL-4, IL-27, IL-28, IFN-γ and IL-1α).