Live attenuated vaccination protects aged chimeric ACE2 mice from severe SARS-CoV-2 pathogenicity in vivo
Fig 2
Generation of a novel chimeric ACE2 mouse model by forward directed mutagenesis.
Structural analysis of the interactions formed between the SARS-CoV-2 RBD and (A) murine (m) ACE2 or (B) human (h) ACE2. The SARS-CoV-2 RBD and ACE2 are shown in cyan and blue, respectively. The four residues, which differ between hACE2 and mACE2, as well as their spatially adjacent residues within the RBDs are explicitly labeled. In hACE2, the four residues form strong polar intermolecular interactions (thick green lines). In mACE2 these polar interactions are either weaker (thin green lines) or completely absent. In addition, an unfavorable steric clash is observed between N31 and F456 of RBD and mACE2 (red arrow). (C) Alignment of the human, murine and chimeric ACE2 amino acid sequences, created with the UniProt Align tool. Blue numbers indicate the amino acid position within mACE2. Grey boxes highlight the amino acids, which have been changed to create a human/mouse chimeric receptor (chACE2). (D) Immunoblot analysis of ACE2 expression in lung and brain tissue of eight weeks old chACE2, K18-ACE2, and C57BL/6 mice.