ACE2 binding is an ancestral and evolvable trait of sarbecoviruses View Full Text


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Article Info

DATE

2022-02-03

AUTHORS

Tyler N. Starr, Samantha K. Zepeda, Alexandra C. Walls, Allison J. Greaney, Sergey Alkhovsky, David Veesler, Jesse D. Bloom

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. More... »

PAGES

913-918

References to SciGraph publications

  • 2020-07-28. Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic in NATURE MICROBIOLOGY
  • 2020-08-25. Origin and cross-species transmission of bat coronaviruses in China in NATURE COMMUNICATIONS
  • 2020-03-26. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins in NATURE
  • 2007-01-31. High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method in NATURE PROTOCOLS
  • 2015-11-09. A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence in NATURE MEDICINE
  • 2020-08-27. A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures in NATURE
  • 2007-01-31. Large-scale high-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method in NATURE PROTOCOLS
  • 2020-02-24. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses in NATURE MICROBIOLOGY
  • 2021-01-25. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis in NATURE
  • 2016-03-09. Sort-seq under the hood: implications of design choices on large-scale characterization of sequence-function relations in BMC GENOMICS
  • 2003-11. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus in NATURE
  • 2021-07-19. Metagenomic identification of a new sarbecovirus from horseshoe bats in Europe in SCIENTIFIC REPORTS
  • 2021-07-19. Broad sarbecovirus neutralization by a human monoclonal antibody in NATURE
  • 2019-06-03. Structural basis for human coronavirus attachment to sialic acid receptors in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2021-11-09. A novel SARS-CoV-2 related coronavirus in bats from Cambodia in NATURE COMMUNICATIONS
  • 2018-12-10. Origin and evolution of pathogenic coronaviruses in NATURE REVIEWS MICROBIOLOGY
  • 2020-02-03. A pneumonia outbreak associated with a new coronavirus of probable bat origin in NATURE
  • 2021-07-14. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape in NATURE
  • 2021-09-17. The biological and clinical significance of emerging SARS-CoV-2 variants in NATURE REVIEWS GENETICS
  • 2013-10-30. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor in NATURE
  • 2004-05. Resurrecting ancient genes: experimental analysis of extinct molecules in NATURE REVIEWS GENETICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41586-022-04464-z

    DOI

    http://dx.doi.org/10.1038/s41586-022-04464-z

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35114688


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