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The SARS-Coronavirus-host interactome: Identification of cyclophilins as target for pan-Coronavirus inhibitors
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نویسنده
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pfefferle s. ,schöpf j. ,kögl m. ,friedel c.c. ,müller m.a. ,carbajo-lozoya j. ,stellberger t. ,von dall'armi e. ,herzog p. ,kallies s. ,niemeyer d. ,ditt v. ,kuri t. ,züst r. ,pumpor k. ,hilgenfeld r. ,schwarz f. ,zimmer r. ,steffen i. ,weber f. ,thiel v. ,herrler g. ,thiel h.-j. ,schwegmann-weßels c. ,pöhlmann s. ,haas j. ,drosten c. ,von brunn a.
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منبع
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plos pathogens - 2011 - دوره : 7 - شماره : 10
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چکیده
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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. © 2011 pfefferle et al.
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آدرس
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bernhard-nocht-institute,hamburg,germany,institute of virology,university of bonn,bonn, Germany, max-von-pettenkofer institute,ludwig-maximilians-university (lmu) munich,münchen, Germany, dkfz,heidelberg, Germany, institute for informatics,lmu munich,münchen,germany,institute of pharmacy and molecular biotechnology,heidelberg university,heidelberg, Germany, institute of virology,university of bonn,bonn, Germany, max-von-pettenkofer institute,ludwig-maximilians-university (lmu) munich,münchen, Germany, max-von-pettenkofer institute,ludwig-maximilians-university (lmu) munich,münchen, Germany, max-von-pettenkofer institute,ludwig-maximilians-university (lmu) munich,münchen, Germany, institute of virology,university of bonn,bonn, Germany, institute of virology,university of bonn,bonn, Germany, institute of virology,university of bonn,bonn, Germany, institute of virology,university of bonn,bonn, Germany, immh,albert-ludwigs-university-freiburg,freiburg, Germany, institute of immunobiology,kantonsspital st. gallen, Switzerland, institute of biochemistry,university of luebeck,luebeck, Germany, institute of biochemistry,university of luebeck,luebeck, Germany, dkfz,heidelberg, Germany, institute for informatics,lmu munich,münchen, Germany, institute of virology,hannover medical school,hannover, Germany, immh,albert-ludwigs-university-freiburg,freiburg,germany,institute of virology,philipps-universität marburg,marburg, Germany, institute of immunobiology,kantonsspital st. gallen, Switzerland, institute of virology,tierärztliche hochschule hannover,hannover, Germany, institute for virology,fachbereich veterinärmedizin,justus-liebig universität gießen,giessen, Germany, institute of virology,tierärztliche hochschule hannover,hannover, Germany, institute of virology,hannover medical school,hannover, Germany, max-von-pettenkofer institute,ludwig-maximilians-university (lmu) munich,münchen,germany,division of pathway medicine,university of edinburgh,edinburgh, United Kingdom, institute of virology,university of bonn,bonn, Germany, max-von-pettenkofer institute,ludwig-maximilians-university (lmu) munich,münchen, Germany
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Authors
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