title: Identification of entry inhibitors of Ebola virus pseudotyped vectors from a myxobacterial compound library.
abstract: Myxobacteria produce secondary metabolites many of which were described to have various biological effects including anti-fungal, anti-bacterial and anti-viral activity. The majority of these metabolites are novel scaffolds with unique modes-of-action and hence might be potential leads for drug discovery. Here, we tested a myxobacterial natural product library for compounds with inhibitory activity against Ebola virus (EBOV). The assay was performed with a surrogate system using Ebola envelope glycoprotein (GP) pseudotyped lentiviral vectors. EBOV specificity was proven by counter-screening with vesicular stomatitis virus G protein pseudotyped vectors. Two compounds were identified that preferentially inhibited EBOV GP mediated cell entry: Chondramides that act on the actin skeleton but might be too toxic and noricumazole A, a potassium channel inhibitor, which might constitute a novel pathway to inhibit Ebola virus cell entry.
authors.affiliation: Paul-Ehrlich-Institut, Department of Virology, Paul-Ehrlich Strasse 51-59, 63225 Langen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Beck
authors.affiliation: Paul-Ehrlich-Institut, Department of Virology, Paul-Ehrlich Strasse 51-59, 63225 Langen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Henß
authors.affiliation: Paul-Ehrlich-Institut, Department of Virology, Paul-Ehrlich Strasse 51-59, 63225 Langen, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Weidner
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland, Microbial Natural Products, Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Herrmann
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland, Microbial Natural Products, Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Pharmacy - Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Germany.
authors.forename: Yu-Kai
authors.initials: YK
authors.lastname: Chao
authors.affiliation: Department of Pharmacy - Center for Drug Research and Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians-Universität München, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grimm
authors.affiliation: Paul-Ehrlich-Institut, Department of Virology, Paul-Ehrlich Strasse 51-59, 63225 Langen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Weber
authors.affiliation: Paul-Ehrlich-Institut, Department of Virology, Paul-Ehrlich Strasse 51-59, 63225 Langen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Sliva
authors.affiliation: Paul-Ehrlich-Institut, Department of Virology, Paul-Ehrlich Strasse 51-59, 63225 Langen, Germany. Electronic address: Barbara.Schnierle@pei.de.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Schnierle
mesh_terms: D000199:Actins / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D029043:Ebolavirus / Q000187:drug effects* / Q000502:physiology*; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy / Q000821:virology; D006801:Humans; D009231:Myxococcales / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000199:Actins; D000998:Antiviral Agents; D001688:Biological Products; D054852:Small Molecule Libraries; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus