Nature research paper: ACE2 binding is an ancestral and evolvable trait of sarbecoviruses
. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 via the spike receptor-binding domain . However, binding to ACE2 orthologs from humans, bats, and other species has been observed only sporadically among the broader diversity of bat sarbecovirusesto trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologs. We find that ACE2 binding is an ancestral trait of sarbecovirus RBDs that has subsequently been lost in some clades.
Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind ACE2. Moreover, ACE2 binding is highly evolvable: for many sarbecovirus RBDs there are single amino-acid mutations that enable binding to new ACE2 orthologs. However, the effects of individual mutations can differ markedly between viruses, as illustrated by the N501Y mutation which enhances human ACE2 binding affinity of several SARS-CoV-2 variants of concernbut severely dampens it for SARS-CoV-1.
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