It was demonstrated that these mutations were viral adaptations to either human or civet ACE2.14,16 A pseudotyped viral infection assay of the interaction between different spike proteins and ACE2 confirmed the correlation between high affinity mutants and their high infection.16 Further investigation of RBD residues in binding of SARS-COV and ACE2 was performed through ala-scanning mutagenesis, which resulted in identification of residues that reduce binding affinity to ACE2 upon mutation to alanine.17 RBD mutations have also been identified in MERS-COV, which affected their affinity to receptor (DPP4) on human cells.14 Multiple monoclonal antibodies have been developed for SARS since 2002 that neutralized the spike glycoprotein on the SARS-COV surface.18−22 However, multiple escape mutations exist in the RBD of SARS-COV that affect neutralization with antibodies, which led to the use of a cocktail of antibodies as a robust treatment.23