Featuring ACE2 binding SARS-CoV and SARS-CoV-2 through a conserved evolutionary pattern of amino acid residues

Carvalho, Patricia P. D.; Alves, Nelson A.

Coronaviruses attach to host cell surface receptors via their spike (S) proteins to mediate the entry into the host cell. The S1 coronavirus 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), which is part of RBD and 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 amino acid 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.