Single-mutation H41Y or E42Q could dramatically render the receptor activity of marmoset or tufted capuchin ACE2 orthologs, and double-mutations YQ (H41Y and E42Q) further increased the A549 cells permissiveness to infection (Fig. 4 D and E), demonstrating that altering the residues at position 41 or 42 into human counterparts confers the ability of New World monkeys ACE2 orthologs of binding to SARS-CoV-2 spike protein and mediating viral entry. Here, ACE2 is linked to infection.