About: Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus
Creator	Drosten, Christian Pöhlmann, Stefan Hoffmann, Markus Kleine-Weber, Hannah Krüger, Nadine »more»
source	Medline; PMC
abstract	Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) causes a severe respiratory disease in humans. The MERS-CoV spike (S) glycoprotein mediates viral entry into target cells. For this, MERS-CoV S engages the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and the interface between MERS-CoV S and DPP4 has been resolved on the atomic level. Here, we asked whether naturally-occurring polymorphisms in DPP4, that alter amino acid residues required for MERS-CoV S binding, influence cellular entry of MERS-CoV. By screening of public databases, we identified fourteen such polymorphisms. Introduction of the respective mutations into DPP4 revealed that all except one (Δ346-348) were compatible with robust DPP4 expression. Four polymorphisms (K267E, K267N, A291P and Δ346-348) strongly reduced binding of MERS-CoV S to DPP4 and S protein-driven host cell entry, as determined using soluble S protein and S protein bearing rhabdoviral vectors, respectively. Two polymorphisms (K267E and A291P) were analyzed in the context of authentic MERS-CoV and were found to attenuate viral replication. Collectively, we identified naturally-occurring polymorphisms in DPP4 that negatively impact cellular entry of MERS-CoV and might thus modulate MERS development in infected patients.
has issue date	2020-01-21(xsd:dateTime)
bibo:doi	10.1080/22221751.2020.1713705
bibo:pmid	31964246
has license	cc-by
sha1sum (hex)	5b31a92b9c0bbc361c12fb2c00bcb17ff3fab61c
schema:url	https://doi.org/10.1080/22221751.2020.1713705
resource representing a document's title	Polymorphisms in dipeptidyl peptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus
has PubMed Central identifier	PMC7006675
has PubMed identifier	31964246
schema:publication	Emerg Microbes Infect
resource representing a document's body	covid:5b31a92b9c0bbc361c12fb2c00bcb17ff3fab61c#body_text
is schema:about of	named entity 'robust' named entity 'engages' named entity 'MERS-CoV' named entity 'vectors' named entity 'host cell protein' »more»

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