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Commun Biol . Determinants of species-specific utilization of ACE2 by human and animal coronaviruses

tetano

Editor, Senior Moderator
Commun Biol


. 2023 Oct 17;6(1):1051.
doi: 10.1038/s42003-023-05436-3. Determinants of species-specific utilization of ACE2 by human and animal coronaviruses

Qingxing Wang[SUP] 1 [/SUP], Sabrina Noettger[SUP] 1 [/SUP], Qinya Xie[SUP] 1 [/SUP], Chiara Pastorio[SUP] 1 [/SUP], Alina Seidel[SUP] 1 [/SUP], Janis A Müller[SUP] 1 2 [/SUP], Christoph Jung[SUP] 3 4 5 [/SUP], Timo Jacob[SUP] 3 4 5 [/SUP], Konstantin M J Sparrer[SUP] 1 [/SUP], Fabian Zech[SUP] 1 [/SUP], Frank Kirchhoff[SUP] 6 [/SUP]



Affiliations
Abstract

Utilization of human ACE2 allowed several bat coronaviruses (CoVs), including the causative agent of COVID-19, to infect humans directly or via intermediate hosts. However, the determinants of species-specific differences in ACE2 usage and the frequency of the ability of animal CoVs to use human ACE2 are poorly understood. Here we applied VSV pseudoviruses to analyze the ability of Spike proteins from 26 human or animal CoVs to use ACE2 receptors across nine reservoir, potential intermediate and human hosts. We show that SARS-CoV-2 Omicron variants evolved towards more efficient ACE2 usage but mutation of R493Q in BA.4/5 and XBB Spike proteins disrupts utilization of ACE2 from Greater horseshoe bats. Variations in ACE2 residues 31, 41 and 354 govern species-specific differences in usage by coronaviral Spike proteins. Mutation of T403R allows the RaTG13 bat CoV Spike to efficiently use all ACE2 orthologs for viral entry. Sera from COVID-19 vaccinated individuals neutralize the Spike proteins of various bat Sarbecoviruses. Our results define determinants of ACE2 receptor usage of diverse CoVs and suggest that COVID-19 vaccination may protect against future zoonoses of bat coronaviruses.


 
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