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onsdag 12 november 2014

EBOV pitää runsasta musiinimolekyyli ja glykaanipuskaa fysikaalisena suojanaan, kuin sokerikakkua ympärillään

  EBOV viruksen  tapa pitää  suurta puskikkoa molekyylejä fysikaalisena suojana samalla viittaisi siihen että sen  soluunpääsyrakenteessa on kriittisiä heikkoja kohtia.joihin voitaisiin  vaikuttaa, kun ne löytää. Tosin se on  napannut  virioneihin muaan ihmissolun lipidiraftista pintamerkitsijämolekyyejä,  jotka  signaloivat  ihmisenlle tyypillistä  tunnusmerkkiä, mikä harhauttaa immunologista  tunnistamista, esim. tunnistaja  solut eivät ehdi  käsittää että kyseesä on  ei-ihmisperäinen vieraskappale.  saati sitten kun  virus metastasoi kehossa- sen virioneja ei tunista, koska ne esittää  "oman  itsen"  merkkejä. Se purkaa  virionit ja  harhautuskappaleet VLP  lipidirafteista, joissa on paljon kehotunnusmerkkejä.

The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry

  1. Thomas von Hahn1,2,*
+ Author Affiliations
  1. 1Institute for Molecular Biology, Hannover Medical School, Hannover, Germany
  2. 2Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
  3. 3Institute for Virology, University of Marburg, Marburg, Germany
  4. 4Infection Biology Unit, German Primate Center, Göttingen, Germany
  5. 5Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany
  6. 6Department of Nephrology, Hannover Medical School, Hannover, Germany
  1. *Corresponding author. Hannover Medical School, Institute for Molecular Biology, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Tel: +49-511-532-4585; Fax: +49-511-532-4896; E-mail: vonhahn.thomas@mh-hannover.de
  • Received December 4, 2013.
  • Revision requested January 21, 2014.
  • Revision received March 2, 2014.
  • Accepted March 7, 2014.
Abstract
Objectives Filoviruses such as Ebola virus and Marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties.
Methods We used authentic filoviruses and lentiviral particles pseudotyped with filoviral glycoproteins to identify and characterize such compounds.
Results We discovered that amiodarone, a multi-ion channel inhibitor and adrenoceptor antagonist, is a potent inhibitor of filovirus cell entry at concentrations that are routinely reached in human serum during anti-arrhythmic therapy. A similar effect was observed with the amiodarone-related agent dronedarone and the L-type calcium channel blocker verapamil. Inhibition by amiodarone was concentration dependent and similarly affected pseudoviruses as well as authentic filoviruses. Inhibition of filovirus entry was observed with most but not all cell types tested and was accentuated by the pre-treatment of cells, indicating a host cell-directed mechanism of action. The New World arenavirus Guanarito was also inhibited by amiodarone while the Old World arenavirus Lassa and members of the Rhabdoviridae (vesicular stomatitis virus) and Bunyaviridae (Hantaan) families were largely resistant.
Conclusions The ion channel blockers amiodarone, dronedarone and verapamil inhibit filoviral cell entry.

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