title: The synergistic effects of betulin with acyclovir against herpes simplex viruses.
abstract: Betulin, a pentacyclic triterpenoid, was isolated from the bark of Betula papyrifera. The antiviral efficacies of betulin on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were evaluated using viral plaque reduction assays on Vero cells. The results indicate that betulin is active against both HSV-1 and HSV-2 infections with the 50% effective concentrations (EC(50)) of 0.40 and 4.15 microg/ml, respectively. The cytotoxicity of betulin was examined on Vero cells using a neutral red uptake assay. The 50% cytotoxic concentration (CC(50)) of betulin was 73.1 microg/ml. A synergistic antiviral effect between betulin and acyclovir (ACV) was determined by drug combination studies. Strong and moderate synergistic antiviral effects were observed for betulin and ACV against HSV-1 when the concentrations of ACV and betulin were higher than 0.068 and 0.4 microg/ml, respectively. At the concentrations lower than these, additive effect was found. Synergistic antiviral effects were also found against HSV-2 at higher concentrations than for HSV-1, i.e. 0.45 microg/ml of ACV combined with 8.4 microg/ml of betulin.
authors.affiliation: Viridae Clinical Sciences Inc., 1134 Burrard Street, Vancouver, BC, Canada V6Z 1Y8. gongyh@hotmail.com
authors.forename: Yunhao
authors.initials: Y
authors.lastname: Gong
authors.forename: Karim M
authors.initials: KM
authors.lastname: Raj
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Luscombe
authors.forename: Izabelle
authors.initials: I
authors.lastname: Gadawski
authors.forename: Teresa
authors.initials: T
authors.lastname: Tam
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chu
authors.forename: David
authors.initials: D
authors.lastname: Gibson
authors.forename: Robert
authors.initials: R
authors.lastname: Carlson
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Sacks
mesh_terms: D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D014315:Triterpenes / Q000494:pharmacology*; D014709:Vero Cells; D010948:Viral Plaque Assay; D000094062:Betulinic Acid
chemical_list: D000212:Acyclovir; D000998:Antiviral Agents; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid