  Spike (S) glycoproteins mediate the coronavirus entry into the host cell. The
S1 subunit of S-proteins contains the receptor-binding domain (RBD) that is
able to recognize different host receptors, highlighting its remarkable
capacity to adapt to their hosts along the viral evolution. While RBD in spike
proteins is determinant for the virus-receptor interaction, the active residues
lie at the receptor-binding motif (RBM), a region located in RBD that plays a
fundamental role binding the outer surface of their receptors. Here, we address
the hypothesis that SARS-CoV and SARS-CoV-2 strains able to use
angiotensin-converting enzyme 2 (ACE2) proteins have adapted their RBM along
the viral evolution to explore specific conformational topology driven by the
residues YGF to infect host cells. We also speculate that this YGF-based
mechanism can act as a protein signature located at the RBM to distinguish
coronaviruses able to use ACE2 as a cell entry receptor.
