OmniVira

ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses.

Nicholas J Catanzaro1 Ziyan Wu2 Chengcheng Fan2 Victoria Jefferson3 Anfal Abdelgadir1 Alexandra Schäfer1 Boyd L Yount1 Pamela J Bjorkman2 Ralph Baric1,4 Michael Letko5
Affiliations 5 institutions
  1. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  2. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  3. Paul G. Allen School for Global Health, Washington State University, Pullman, WA, USA.
  4. Department of Epidemiology, Gillings School of Global Public Heath, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  5. Paul G. Allen School for Global Health, Washington State University, Pullman, WA, USA. [email protected].
PMID40436893 DOI10.1038/s41467-025-60286-3 Year2025 Journal Nature communications Nat Commun Languageeng Publication statusActive
Active Last checked 2026-10-01 03:31:09 Source: NCBI PubMed

Abstract

The merbecovirus subgenus of coronaviruses includes Middle East Respiratory Syndrome Coronavirus (MERS-CoV), a zoonotic pathogen transmitted from dromedary camels to humans that causes severe respiratory disease. Viral discovery efforts uncover hundreds of merbecoviruses in different species across multiple continents, but few are studied under laboratory conditions, leaving basic questions regarding their human threat potential unresolved. Viral entry into host cells is a critical step for transmission between hosts. Here, we develop and apply a scalable approach to assesses novel merbecovirus cell entry across the entire merbecovirus subgenus. Merbecoviruses are sorted into clades based on the receptor-binding domain of the spike glycoprotein. Receptor tropism is clade-specific, with the clade including MERS-CoV using DPP4 and multiple clades using ACE2, including HKU5 bat coronaviruses. Mutational analysis identifies possible structural limitations to HKU5 adaptability and a cryo-EM structure of the HKU5-20s spike trimer reveals only 'down' RBDs.

Supporting text Virus Host Location
Angiotensin-Converting Enzyme 2 178 Chiroptera 376 Coronavirus 93 Receptors, Virus 208 Animals 1981 Cryoelectron Microscopy 37 Dipeptidyl Peptidase 4 32 HEK293 Cells 61 Humans 1455 Middle East Respiratory Syndrome Coronavirus 69 Phylogeny 826 Spike Glycoprotein, Coronavirus 276 Viral Tropism 46 Virus Internalization 100

Evidence records

2 total
Functional Mechanism
2 records · 1 evidence types
Evidence type Receptor Usage
2 records
OVE9347 Receptor Usage
Key finding

MERS-CoV uses DPP4 as its receptor for cell entry, whereas HKU5 bat coronaviruses use ACE2.

Virus
Middle East Respiratory Syndrome Coronavirus bat coronavirus HKU5
Host
Not specified
Location
Not specified
Supporting text

Receptor tropism is clade-specific, with the clade including MERS-CoV using DPP4 and multiple clades using ACE2, including HKU5 bat coronaviruses.

Method
receptor binding assays | viral entry assays
Receptors
DPP4 | ACE2