2. Academic Validation
  3. The sphingosine kinase 1 activator, K6PC-5, attenuates Ebola virus infection

The sphingosine kinase 1 activator, K6PC-5, attenuates Ebola virus infection

  • iScience. 2021 Mar 5;24(4):102266. doi: 10.1016/j.isci.2021.102266.
Gergely Imre 1,  Verena Krähling 2 3,  Madeleine Eichler 1,  Sandra Trautmann 4,  Nerea Ferreirós 4,  M Javad Aman 5,  Fatah Kashanchi 6,  Krishnaraj Rajalingam 7,  Stefan Pöhlmann 8 9,  Stephan Becker 2 3,  Dagmar Meyer Zu Heringdorf 1,  Josef Pfeilschifter 1
Affiliations

Affiliations

  • 1 Institute of General Pharmacology and Toxicology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main 60590, Germany.
  • 2 Institute of Virology, Philipps University Marburg, Marburg, Germany.
  • 3 German Center for Infection Research (DZIF), partner site Gießen-Marburg-Langen, Marburg, Germany.
  • 4 Institute of Clinical Pharmacology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main 60590, Germany.
  • 5 Integrated BioTherapeutics, Inc., Gaithersburg, MD 20850, USA.
  • 6 Laboratory of Molecular Virology, George Mason University Manassas, VA 20110, USA.
  • 7 Cell Biology Unit, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
  • 8 Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, 37077 Göttingen, Germany.
  • 9 Faculty of Biology and Psychology, University Göttingen, 37077 Göttingen, Germany.
PMID: 33817572 DOI: 10.1016/j.isci.2021.102266
Abstract

Ebola virus (EBOV) is responsible for outbreaks with case fatality rates of up to 90% and for an epidemic in West Africa with more than ten thousand deaths. EBOV glycoprotein (EBOV-GP) is the only viral surface protein and is responsible for viral entry into cells. Here, by employing pseudotyped EBOV-GP viral particles, we uncover a critical role for sphingolipids in inhibiting viral entry. Sphingosine kinase 1 (SphK1) catalyzes the phosphorylation of sphingosine to sphingosine 1-phosphate (S1P). The administration of the SphK1 Activator, K6PC-5, or S1P, or the overexpression of SphK1 consistently exhibited striking inhibitory effects in EBOV-GP-driven entry in diverse cell lines. Finally, K6PC-5 markedly reduced the EBOV titer in infected cells and the de novo production of Viral Proteins. These data present K6PC-5 as an efficient tool to inhibit EBOV Infection in endothelial cells and suggest further studies to evaluate its systemic effects.

Keywords

Cell Biology; Molecular Microbiology; Virology.

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