Exceptional diversity and selection pressure on coronavirus host receptors in bats compared to other mammals

Hannah K. Frank, David Enard, Scott D. Boyd

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Pandemics originating from non-human animals highlight the need to understand how natural hosts have evolved in response to emerging human pathogens and which groups may be susceptible to infection and/or potential reservoirs to mitigate public health and conservation concerns. Multiple zoonotic coronaviruses, such as severe acute respiratory syndrome-associated coronavirus (SARS-CoV), SARS-CoV-2 and Middle Eastern respiratory syndrome-associated coronavirus (MERS-CoV), are hypothesized to have evolved in bats. We investigate angiotensin-converting enzyme 2 (ACE2), the host protein bound by SARS-CoV and SARS-CoV-2, and dipeptidyl-peptidase 4 (DPP4 or CD26), the host protein bound by MERS-CoV, in the largest bat datasets to date. Both the ACE2 and DPP4 genes are under strong selection pressure in bats, more so than in other mammals, and in residues that contact viruses. Additionally, mammalian groups vary in their similarity to humans in residues that contact SARS-CoV, SARS-CoV-2 and MERS-CoV, and increased similarity to humans in binding residues is broadly predictive of susceptibility to SARS-CoV-2. This work augments our understanding of the relationship between coronaviruses and mammals, particularly bats, provides taxonomically diverse data for studies of how host proteins are bound by coronaviruses and can inform surveillance, conservation and public health efforts.

Original languageEnglish (US)
Article number20220193
JournalProceedings of the Royal Society B: Biological Sciences
Issue number1979
StatePublished - Jul 27 2022


  • ACE2
  • COVID-19
  • Chiroptera
  • DPP4
  • SARS-CoV-2
  • molecular evolution

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Environmental Science
  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology

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