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

• Published in: Journal of allergy and clinical immunology Vol. 137; no. 1; pp. 197 - 203.e3
• Main Authors: Mader, Julia, Gallo, Antonio, Schommartz, Tim, Handke, Wiebke, Nagel, Claus-Henning, Günther, Patrick, Brune, Wolfram, Reich, Kristian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016; Elsevier Limited
• Subjects: Adult; Aged; Algae; Allergy and Immunology; Animals; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Calcium; calcium spirulan; Cell Line; Cercopithecus aethiops; Cosmetics; Epithelial Cells - drug effects; Epithelial Cells - virology; Female; herpes labialis; Herpes Labialis - prevention & control; Herpes simplex virus 1; Herpes viruses; Herpesvirus; 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; Infections; Kaposi sarcoma; Kaposi sarcoma–associated herpesvirus/human herpes virus 8; keratinocytes; Keratinocytes - drug effects; Keratinocytes - virology; Methods; Middle Aged; Polysaccharides - pharmacology; Polysaccharides - therapeutic use; Spirulina; Spirulina microalgae; Spirulina platensis; Vero Cells; Viral infections; Virus Attachment - drug effects; Young Adult; Germany; KSHV/HHV-8; MOI; HSV; keratinocytes; TCID50; herpes labialis; Ca-SP; Herpes simplex virus 1; Kaposi sarcoma; CHX; SPME; ACV; Spirulina microalgae; calcium spirulan; IC50; PMU; Kaposi sarcoma–associated herpesvirus/human herpes virus 8; pfu; PRA; IC 50; Plaque-forming units; Herpes simplex virus; Half-maximal inhibitory concentration; Plaque reduction assay; 50% Tissue culture infective dose; Multiplicity of infection; Acyclovir; Permanent lip makeup; Cycloheximide; TCID 50; Spirulina platensis microalgae extract
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2015.07.027

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