Calcium spirulan derived from Spirulina platensis inhibits herpes simplex virus 1 attachment to human keratinocytes and protects against herpes labialis

J Allergy Clin Immunol. 2016 Jan;137(1):197-203.e3. doi: 10.1016/j.jaci.2015.07.027. Epub 2015 Sep 2.


Background: Chronic infections with herpes simplex virus (HSV) type 1 are highly prevalent in populations worldwide and cause recurrent oral lesions in up to 40% of infected subjects.

Objective: We investigated the antiviral activity of a defined Spirulina platensis microalga extract and of purified calcium spirulan (Ca-SP), a sulfated polysaccharide contained therein.

Methods: The inhibitory effects of HSV-1 were assessed by using a plaque reduction assay and quantitative PCR in a susceptible mammalian epithelial cell line and confirmed in human keratinocytes. Time-of-addition and attachment experiments and fluorescence detection of the HSV-1 tegument protein VP16 were used to analyze the mechanism of HSV-1 inhibition. Effects of Ca-SP on Kaposi sarcoma-associated herpesvirus/human herpes virus 8 replication and uptake of the ORF45 tegument protein were tested in human retinal pigment epithelial cells. In an observational trial the prophylactic effects of topically applied Ca-SP were compared with those of systemic and topical nucleoside analogues in 198 volunteers with recurrent herpes labialis receiving permanent lip makeup.

Results: Ca-SP inhibited HSV-1 infection in vitro with a potency at least comparable to that of acyclovir by blocking viral attachment and penetration into host cells. Ca-SP also inhibited entry of Kaposi sarcoma-associated herpesvirus/human herpes virus 8. In the clinical model of herpes exacerbation, the prophylactic effect of a Ca-SP and microalgae extract containing cream was superior to that of acyclovir cream.

Conclusion: These data indicate a potential clinical use of Ca-SP containing Spirulina species extract for the prophylactic treatment of herpes labialis and suggest possible activity of Ca-SP against infections caused by other herpesviruses.

Keywords: Herpes simplex virus 1; Kaposi sarcoma; Kaposi sarcoma–associated herpesvirus/human herpes virus 8; Spirulina microalgae; calcium spirulan; herpes labialis; keratinocytes.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use*
  • Cell Line
  • Chlorocebus aethiops
  • Cosmetics
  • Epithelial Cells / drug effects
  • Epithelial Cells / virology
  • Female
  • Herpes Labialis / prevention & control*
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / pathogenicity
  • Herpesvirus 1, Human / physiology
  • Herpesvirus 8, Human / drug effects
  • Herpesvirus 8, Human / pathogenicity
  • Herpesvirus 8, Human / physiology
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / virology
  • Middle Aged
  • Polysaccharides / pharmacology*
  • Polysaccharides / therapeutic use*
  • Spirulina*
  • Vero Cells
  • Virus Attachment / drug effects
  • Young Adult


  • Antiviral Agents
  • Cosmetics
  • Polysaccharides
  • spirulan