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Abstract

Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in PR China in late 2019 a number of variants have emerged, with two of these – alpha and delta – subsequently growing to global prevalence. One characteristic of these variants are changes within the spike protein, in particular the receptor-binding domain (RBD). From a public health perspective, these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host range of the virus. Using viral pseudotyping, we examined whether the variants of concern (VOCs) alpha, beta, gamma and delta have differing host angiotensin-converting enzyme 2 (ACE2) receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes that we subsequently attributed to N501Y and E484K substitutions within the spike RBD.

Funding
This study was supported by the:
  • Medical Research Council (Award MR/W005611/1)
    • Principle Award Recipient: DalanBailey
  • Medical Research Council (Award MR/V036750/1)
    • Principle Award Recipient: CatherineN Hall
  • Biotechnology and Biological Sciences Research Council (Award BB/T008784/1)
    • Principle Award Recipient: NaziaThakur
  • Biotechnology and Biological Sciences Research Council (Award BBS/E/I/00007034)
    • Principle Award Recipient: DalanBailey
  • Biotechnology and Biological Sciences Research Council (Award BBS/E/I/00007038)
    • Principle Award Recipient: DalanBailey
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-04-04
2024-05-21
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