At first glance, HCoV-NL63 and SARS-CoV S1-CTDs very different. The core structure of HCoV-NL63 S1-CTD is a β-sandwich consisting of two β-sheet layers stacked together through hydrophobic interactions, which is in contrast to the single β-sheet layer in the core structure of SARS-CoV S1-CTD. Their RBM is also different. The RBM of HCoV-NL63 S1-CTD are three short and discontinuous loops, whereas the RBM of SARS-CoV S1-CTD is a single long and continuous subdomain. Indeed, the protein-folding Dali server failed to detect any structuural similarity between HCoV-NL63 and SARS-CoV S1-CTDs.