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.
SARS-CoV-2 variants alpha, beta, gamma, and delta show extended ACE2 receptor usage, enabling entry via mouse, rat, ferret, and civet ACE2 proteins due to N501Y and E484K mutations in the spike receptor-binding domain.
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.
Method
viral pseudotyping
Receptors
ACE2
Host factors
N501Y; E484K
Receptor UsageExtraction confidence 1.00
Key finding
SARS-CoV-2 variants of concern exhibit variant-specific ACE2 receptor interactions with rat, ferret, and civet ACE2 proteins, indicating altered receptor compatibility among mammalian hosts.
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 ... 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.
Method
viral pseudotyping; receptor-usage assay
Experimental system
pseudovirus assay
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.95
Key finding
N501Y and E484K substitutions in the SARS-CoV-2 spike RBD mediate expanded ACE2 receptor usage, allowing variants of concern to overcome previous host receptor restrictions and broaden host range.
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.
