Compared with ACE2, the much higher anti-SARS-CoV-2 potency of Nanosota-1C-Fc was partly due to the small size of its antigen-binding domain and its ideal binding site on the RBD, allowing Nanosota-1C-Fc to access the RBD in both the open spike during viral infection and the closed spike during viral immune evasion. This evidence concerns the gene ACE2 and viral infectious disease.