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


CONCLUSIONS
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.
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany; Dermatologikum Hamburg, Hamburg, Germany.
Julia
J
Mader
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Antonio
A
Gallo
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Tim
T
Schommartz
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Wiebke
W
Handke
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Claus-Henning
CH
Nagel
Ocean Pharma GmbH, Reinbek, Germany.
Patrick
P
Günther
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg, Hamburg, Germany. Electronic address: wolfram.brune@hpi.uni-hamburg.de.
Wolfram
W
Brune
Dermatologikum Hamburg, Hamburg, Germany. Electronic address: kreich@dermatologikum.de.
Kristian
K
Reich
D000328:Adult; D000368:Aged; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003358:Cosmetics; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D005260:Female; D006560:Herpes Labialis / Q000517:prevention & control*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000821:virology; D008875:Middle Aged; D011134:Polysaccharides / Q000494:pharmacology* / Q000627:therapeutic use*; D053545:Spirulina; D014709:Vero Cells; D053585:Virus Attachment / Q000187:drug effects; D055815:Young Adult
D000998:Antiviral Agents; D003358:Cosmetics; D011134:Polysaccharides; C102617:spirulan
Herpes simplex virus 1; Kaposi sarcoma; Kaposi sarcoma–associated herpesvirus/human herpes virus 8; Spirulina microalgae; calcium spirulan; herpes labialis; keratinocytes