ACE2 and infection: Recognizing that the K18-hACE2 model has changes in viral tropism due to the artificial nature of the hACE2 transgene expression (36), we utilized a SCV2 variant of concern (VOC, beta variant, B.1.351), which carries an asparagine to tyrosine substitution at amino acid 501 of the spike protein, allowing binding to murine ACE2 and establishment of transient SCV2 infection in wild type (WT) C57Bl/6 mice (37, 38).