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

TL;DR

This study investigates the conserved amino acid pattern in the receptor-binding motif of coronavirus spike proteins, revealing a YGF signature that correlates with ACE2 receptor usage in SARS-CoV and SARS-CoV-2.

Contribution

It identifies a conserved YGF amino acid pattern in the RBM that distinguishes ACE2-using coronaviruses and explores its role in viral adaptation and host cell entry.

Findings

YGF pattern is conserved in ACE2-binding coronaviruses.

The YGF motif may serve as a signature for ACE2 receptor utilization.

Evolutionary analysis links YGF to host adaptation mechanisms.

Abstract

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.