Cited by 2,061SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesCOVID-19 Clinical Research Studies

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Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

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Raj, V. Stalin, Mou, Huihui, Smits, Saskia L., Dekkers, Dick H. W., Müller, Marcel A., Dijkman, Ronald, Muth, Doreen, Demmers, Jeroen A. A., Zaki, Ali, Fouchier, Ron A. M., Thiel, Volker, Drosten, Christian, Rottier, Peter J. M., Osterhaus, Albert D. M. E., Bosch, Berend Jan, Haagmans, Bart L.·2013·Nature

DOI 10.1038/nature12005PMC PMC7095326

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Abstract

Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.

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Self-citation
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Authors: Raj, V. S., Mou, H., Smits, S. L., Dekkers, D. H. W., Müller, M. A., Dijkman, R., Muth, D., Demmers, J. A. A., Zaki, A., Fouchier, R. A. M., Thiel, V., Drosten, C., Rottier, P. J. M., Osterhaus, A. D. M. E., Bosch, B. J., & Haagmans, B. L.
Affiliations: Erasmus MC (NL)
Utrecht University (NL)
University of Bonn (DE)
Kantonsspital St. Gallen (CH)
Soliman Fakeeh Hospital (SA)
University of Zurich (CH)
Corresponding author: Bosch, Berend Jan
Haagmans, Bart L.
ORCID: Raj, V. Stalin
Mou, Huihui
Dekkers, Dick H. W.
Müller, Marcel A.
Dijkman, Ronald
Muth, Doreen
Demmers, Jeroen A. A.
Zaki, Ali
Fouchier, Ron A. M.
Thiel, Volker
Drosten, Christian
Osterhaus, Albert D. M. E.
Bosch, Berend Jan
Haagmans, Bart L.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2013-03
Volume: 495
Issue: 7440
Pages: 251-254
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature12005
PMC: PMC7095326
OpenAlex: W2119111857
Cited by: 2,061
References: 25
Citations by year: 2026: 41 · 2025: 64 · 2024: 97 · 2023: 130 · 2022: 199 · 2021: 358 · 2020: 609 · 2019: 74 · 2018: 59 · 2017: 61 · 2016: 93 · 2015: 101 · 2014: 86 · 2013: 87
FWCI: 89.49
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders: National Science Foundation
European Commission (223498, 278976)
Deutsche Forschungsgemeinschaft (DR 772/3-1, KA1241/18-1, 772/3)
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (132898)
Bundesministerium für Bildung und Forschung
China Scholarship Council
Stiftung Forschung 3R (128-11)
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords: MERS-CoV, dipeptidyl peptidase IV, CD26, viral receptor, host range, lower respiratory tract infection, SARS-CoV, receptor binding domain, Huh7 cells, bronchial epithelial cells
MeSH terms: Animals, Chlorocebus aethiops, Chiroptera, Epithelial Cells, Humans, Molecular Sequence Data, Receptors, Virus, Coronavirus, Coronavirus Infections, Dipeptidyl Peptidase 4, COS Cells, Bronchioles, Host Specificity

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