title: The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles.
abstract: Herpes simplex virus (HSV) and many other viruses, including HIV, initiate infection of host cells by binding to glycosaminoglycan (GAG) chains of cell surface proteoglycans. Although GAG mimetics, such as sulfated oligo- and polysaccharides, exhibit potent antiviral activities in cultured cells, the prophylactic application of these inhibitors as vaginal microbicides failed to protect women upon their exposure to HIV. A possible explanation for this failure is that sulfated oligo- and polysaccharides exhibit no typical virucidal activity, as their interaction with viral particles is largely electrostatic and reversible and thereby vulnerable to competition with GAG-binding proteins of the genital tract. Here we report that the cholestanol-conjugated sulfated oligosaccharide PG545, but not several other sulfated oligosaccharides lacking this modification, exhibited virucidal activity manifested as disruption of the lipid envelope of HSV-2 particles. The significance of the virus particle-disrupting activity of PG545 was also demonstrated in experimental animals, as this compound, in contrast to unmodified sulfated oligosaccharide, protected mice against genital infection with HSV-2. Thus, PG545 offers a novel prophylaxis option against infections caused by GAG-binding viruses.
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden said@microbio.gu.se tomas.bergstrom@microbio.gu.se.
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Said
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Edward
authors.initials: E
authors.lastname: Trybala
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Görander
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Ekblad
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Liljeqvist
authors.affiliation: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Jennische
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lange
authors.affiliation: Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden said@microbio.gu.se tomas.bergstrom@microbio.gu.se.
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergström
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006558:Herpes Genitalis / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000494:pharmacology; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D014771:Virion / Q000737:chemistry / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D008055:Lipids; D009844:Oligosaccharides; C557899:PG 545; D012503:Saponins; C120158:phosphomannopentaose sulfate