Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV

PLoS One. 2017 Jun 30;12(6):e0179291. doi: 10.1371/journal.pone.0179291. eCollection 2017.

Abstract

Background: There is a clinical need for new therapeutic products against Herpes simplex virus (HSV). The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE) and co-administered zinc (II) ions.

Materials and methods: PRE was used in conjunction with zinc (II) salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit.

Results: Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1) a value comparable to aciclovir (EC50 = 0.18 μg mL-1); however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1), whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution.

Conclusions: The potentiated virucidal activity of PRE by coadministered zinc (II) has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores.

MeSH terms

  • Acyclovir / pharmacology*
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Chlorocebus aethiops
  • Cytotoxicity, Immunologic / drug effects
  • Drug Resistance, Viral
  • Drug Synergism
  • Ellagic Acid / pharmacology
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / growth & development
  • Herpesvirus 2, Human / drug effects*
  • Herpesvirus 2, Human / growth & development
  • Lythraceae / chemistry*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Vero Cells
  • Viral Plaque Assay
  • Zinc Compounds / administration & dosage
  • Zinc Compounds / pharmacology*

Substances

  • Antiviral Agents
  • Plant Extracts
  • Zinc Compounds
  • Ellagic Acid
  • Acyclovir

Grants and funding

This work was funded by the Welsh Assembly Government RFSSA07-03-013.