ACE2 binding is an ancestral and evolvable trait of sarbecoviruses

Tyler N. Starr (), Samantha K. Zepeda, Alexandra C. Walls, Allison J. Greaney, Sergey Alkhovsky, David Veesler () and Jesse D. Bloom ()
Additional contact information
Tyler N. Starr: Fred Hutchinson Cancer Research Center
Samantha K. Zepeda: University of Washington
Alexandra C. Walls: University of Washington
Allison J. Greaney: Fred Hutchinson Cancer Research Center
Sergey Alkhovsky: Ministry of Health of the Russian Federation
David Veesler: Howard Hughes Medical Institute
Jesse D. Bloom: Fred Hutchinson Cancer Research Center

Nature, 2022, vol. 603, issue 7903, 913-918

Abstract: Abstract Two different sarbecoviruses have caused major human outbreaks in the past two decades1,2. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain2–6. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses7–11. Here we use high-throughput assays12 to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern12 but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.

Date: 2022
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-04464-z Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:603:y:2022:i:7903:d:10.1038_s41586-022-04464-z

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-04464-z

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().