Disturbance of the hot spot stucture via mutagenesis decreased or abolished the binding of both viruses. Hence, Lys353 and the nearby residues on ACE2 form a common virus-binding hot spot that is critical for the attachment of two different coronaviruses. On the other hand, among the three RBMs in HCoV-NL63 S1-CTD, only RBM1 and RBM2, but not RBM3, are involved  in binding the common virus-binding hot spot on ACE2, despite the fact that RBM3 is topologically equivalent to the RBM in SARS-CoV S1-CTD.