Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC
V. Stalin Raj,Huihui Mou,Saskia L. Smits,Dick H. W. Dekkers,Marcel A. Müller,Ronald Dijkman,Doreen Muth,Jeroen Demmers,Ali Moh Zaki,Ron A. M. Fouchier,Volker Thiel,Volker Thiel,Christian Drosten,Peter J. M. Rottier,Albert D. M. E. Osterhaus,Berend Jan Bosch,Bart L. Haagmans +16 more
TLDR
Dipeptidyl peptidase 4 (DPP4; also known as CD26) is identified as a functional receptor for hCoV-EMC and will contribute critically to the understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.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.read more
Citations
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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
Markus Hoffmann,Hannah Kleine-Weber,Simon Schroeder,Nadine Krüger,Tanja Herrler,Sandra Erichsen,Tobias S. Schiergens,Georg Herrler,Nai Huei Wu,Andreas Nitsche,Marcel A. Müller,Christian Drosten,Christian Drosten,Stefan Pöhlmann +13 more
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
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Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.
Alexandra C. Walls,Young-Jun Park,M. Alejandra Tortorici,M. Alejandra Tortorici,Abigail Wall,Andrew T. McGuire,Andrew T. McGuire,David Veesler +7 more
TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
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Origin and evolution of pathogenic coronaviruses
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TL;DR: The viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome are explored and the diversity and potential of bat-borne coronaviruses are highlighted.
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Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus.
TL;DR: These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019- nCoV.
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Coronaviruses: An Overview of Their Replication and Pathogenesis
Anthony R. Fehr,Stanley Perlman +1 more
TL;DR: A brief introduction to coronaviruses is provided discussing their replication and pathogenicity, and current prevention and treatment strategies, and the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratories Syndrome Cor onavirus
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