articleCellFeb 7, 2025HYBRID OA

Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses

YPYoung‐Jun ParkCLChen LiuJLJimin LeeJTJack T BrownCMChengbao Ma

Howard Hughes Medical Institute · University of Washington · +5 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

DPP4 was considered a canonical receptor for merbecoviruses until the recent discovery of African bat-borne MERS-related coronaviruses using ACE2. The extent and diversity of ACE2 utilization among merbecoviruses and their receptor species tropism remain unknown. Here, we reveal that HKU5 enters host cells utilizing Pipistrellus abramus (P.abr) and several non-bat mammalian ACE2s through a binding mode distinct from that of any other known ACE2-using coronaviruses. We defined the molecular determinants of receptor species tropism and identified a single amino acid mutation enabling HKU5 to utilize human ACE2, providing proof of principle for machine-learning-assisted outbreak preparedness. We show that…

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43
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100%
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Authors

17

Topics & keywords

Topics
Keywords
  • Biology
  • Coronavirus disease 2019 (COVID-19)
  • 2019-20 coronavirus outbreak
  • Coronavirus
  • Virology
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  • Computational biology
  • Convergent evolution
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