Antiviral effects of Cacicol®, a heparan sulfate biomimetic for corneal regeneration therapy, for herpes simplex virus type-1 and varicella zoster virus infection

Antivir Ther. 2018;23(8):665-675. doi: 10.3851/IMP3254.

Abstract

Background: Cacicol®, a topical eye biopolymer containing a poly-carboxymethylglucose sulfate solution that is a regenerating matrix therapy agent, intended for wound healing of persistent corneal epithelial defects. Based on the chemical composition, we hypothesized that Cacicol® may compete with natural heparan sulfate (HS) which initiates cell surface attachment of herpes simplex virus type-1 (HSV-1), varicella zoster virus (VZV) and human adenovirus (HAdV), three viruses associated with corneal infections.

Methods: Cacicol® was compared to vehicle in the following viral strains: HSV-1 SC16 strain and HSV-1 PSLR, a clinical isolate highly resistant to acyclovir and foscarnet; VZV ATH and VZV FLO, two VZV clinical isolates; and HAdV-D37 strain. Viruses in Cacicol® or vehicle were added to cells for 1 h during adsorption then viral replication was assessed by plaque reduction assays on Vero cells for HSV-1 and MeWo cells for VZV and by immunostaining assay on Hep-2 cells for HAdV-D37.

Results: The vehicle had no effect, dose-dependent effects were demonstrated when HSV-1 SC16, HSV-1 PSLR, VZV ATH and VZV FLO were inoculated in the presence of Cacicol®, inhibiting viral replication by 98.4%, 98.9%, 90.1% and 89.0%, respectively. Cacicol® had no antiviral effect against HAdV-D37.

Conclusions: Cacicol® has a significant antiviral activity on HSV-1 and VZV, but not on HAdV-D37. The lack of effect on HAdV is probably because it is less dependent on HS interactions for cell entry. Clinical studies are necessary to determine Cacicol® for an adjunct or alternative therapy of corneal HSV-1 or VZV infection, particularly for the management of antiviral resistant HSV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage*
  • Biomimetic Materials
  • Cells, Cultured
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Heparitin Sulfate / administration & dosage*
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 3, Human / drug effects*
  • Keratitis, Herpetic / diagnosis
  • Keratitis, Herpetic / drug therapy
  • Keratitis, Herpetic / virology*
  • Regeneration*
  • Vero Cells
  • Viral Plaque Assay
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Heparitin Sulfate