About: The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors

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About: The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors
Creator	Thiel, Volker Weber, Friedemann Herrler, Georg Drosten, Christian Hilgenfeld, Rolf Carbajo-Lozoya, Javier Schwegmann-Weßels, Christel Zimmer, Ralf Pfefferle, Susanne Niemeyer, Daniela Steffen, Imke Kuri, Thomas Ditt, Vanessa Herzog, Petra Kallies, Stefan Pumpor, Ksenia Schwarz, Frank Stellberger, Thorsten Friedel, Caroline Von Brunn, Albrecht Zü St, Roland Rgen Haas, Jü Kö Gl, Manfred Mü Ller, Marcel Pö Hlmann 10, Stefan Schö Pf, Julia Thiel, Heinz-Jü Rgen Von Dall'armi, Ekatarina
Source	Medline; PMC
abstract	Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock.
has issue date	2011-10-27(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1002331
bibo:pmid	22046132
has license	cc-by
sha1sum (hex)	e92488019ca299d19beabb885c7c71b12b535712
schema:url	https://doi.org/10.1371/journal.ppat.1002331
resource representing a document's title	The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors
has PubMed Central identifier	PMC3203193
has PubMed identifier	22046132
schema:publication	PLoS Pathog
resource representing a document's body	covid:e92488019ca299d19beabb885c7c71b12b535712#body_text
is schema:about of	named entity 'epidemics' named entity 'animal' named entity 'Conversely' named entity 'infectious bronchitis' named entity 'protein' named entity 'Inhibitors' covid:arg/e92488019ca299d19beabb885c7c71b12b535712 named entity 'Overexpression' named entity 'host' named entity 'study' named entity 'interleukin' named entity 'pathogens' named entity 'neurological disease' named entity 'enhanced' named entity 'observed' named entity 'Neither' named entity 'broad-spectrum' named entity '2011' named entity 'targets' named entity 'blocked' named entity 'define' named entity 'SARS' named entity 'cytokine' named entity 'infection' named entity 'non-structural protein' named entity 'SARS-CoV' named entity 'animal pathogens' named entity 'cyclophilins' named entity 'Coronavirus' named entity 'systems biology' named entity 'vaccines' named entity 'PPIA' named entity 'Interactome' named entity 'FKBP1A' named entity 'Cyclophilins' named entity 'epidemics' named entity 'NFAT' named entity 'Coronaviruses' named entity 'PPIG' named entity 'FKBP1B' named entity 'avian infectious bronchitis virus' named entity 'gastrointestinal' named entity 'SARS' named entity 'feline' named entity 'plasmid' named entity 'ethanol' named entity 'NFAT' named entity 'SARS-CoV' named entity 'hydrophobic' named entity 'luciferase' named entity 'cyclophilins' named entity 'proteins expressed' named entity 'FKBP1A' named entity 'negative control'

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