Synthetic Heparanase Inhibitors Can Prevent Herpes Simplex Viral Spread

Abstract: Herpes simplex virus (HSV‐1) employs heparan sulfate (HS) as receptor for cell attachment and entry. During late‐stage infection, the virus induces the upregulation of human heparanase (Hpse) to remove cell surface HS allowing viral spread. We hypothesized that inhibition of Hpse will prevent viral release thereby representing a new therapeutic strategy for HSV‐1. A range of HS‐oligosaccharides was prepared to examine the importance of chain length and 2‐O‐sulfation of iduronic moieties for Hpse inhibition. It was found that hexa‐ and octasaccharides potently inhibited the enzyme and that 2‐O‐sulfation of iduronic acid is tolerated. Computational studies provided a rationale for the observed structure–activity relationship. Treatment of human corneal epithelial cells (HCEs) infected with HSV‐1 with the hexa‐ and octasaccharide blocked viral induced shedding of HS which significantly reduced spread of virions. The compounds also inhibited migration and proliferation of immortalized HCEs thereby providing additional therapeutic properties.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Synthetic Heparanase Inhibitors Can Prevent Herpes Simplex Viral Spread ; day:06 ; month:09 ; year:2023 ; extent:12 ; Angewandte Chemie / International edition. International edition ; (06.09.2023) (gesamt 12)

Beteiligte, Orts- und Zeitangaben

• Urheber: Chopra, Pradeep ; Yadavalli, Tejabhiram ; Palmieri, Francesco ; Jongkees, Seino A. K. ; Unione, Luca ; Shukla, Deepak ; Boons, Geert‐Jan

Weitere Informationen

• DOI: 10.1002/anie.202309838
• URN: urn:nbn:de:101:1-2023090615190196009241
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:48 MESZ