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The Cholestanol-Conjugated Sulfated Oligosaccharide PG545 Disrupts the Lipid Envelope of Herpes Simplex Virus Particles

Journal article
Authors Joanna Said
Edward Trybala
Staffan Görander
Maria Ekblad
Jan-Åke Liljeqvist
Eva Jennische
Stefan Lange
Tomas Bergström
Published in Antimicrobial agents and chemotherapy
Volume 60
Issue 2
Pages 1049-1057
ISSN 1098-6596
Publication year 2016
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Biomedicine, Department of Infectious Medicine
Pages 1049-1057
Language en
Links dx.doi.org/10.1128/AAC.02132-15
Subject categories Clinical virology, Virology, Infectious Medicine

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 activity in cultured cells, the prophylactic application of these inhibitors as vaginal microbicides failed to protect women on their exposure to HIV infection. 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 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. Significance of the virus particle-disrupting activity of PG545 was also documented 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.

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Denna text är utskriven från följande webbsida:
http://www.gu.se/english/research/publication/?publicationId=230289
Utskriftsdatum: 2019-08-19