title: Theaflavin-3,3'-digallate and lactic acid combinations reduce herpes simplex virus infectivity.
abstract: The present study examined the efficacy of using multiple mechanisms as part of a topical microbicide to inactivate herpes simplex virus (HSV) by combining theaflavin-3,3'-digallate (TF-3) and lactic acid (LA) over the pH range of 4.0 to 5.7 to mimic conditions in the female reproductive tract. Six clinical isolates of HSV-2 and two clinical isolates of HSV-1 were almost completely inactivated when TF-3 (100 μM) was present with LA over the pH range of 4.5 to 5.7, whereas four additional HSV-1 clinical isolates required TF-3 concentrations of 250 to 500 μM for comparable virus titer reduction. LA (1%) alone at pH 4.0 reduced the titers of laboratory and clinical isolates of HSV-1 and HSV-2 by ≥ 5 log10, but most LA-dependent antiviral activity was lost at a pH of ≥ 4.5. When HSV-1 and HSV-2 were incubated at pH 4.0 without LA virus titers were not reduced. At pH 4.0, HSV-1 and HSV-2 titers were reduced 5 log(10) in 20 min by LA alone. TF-3 reduced HSV-2 titers by 5 log10 in 20 to 30 min at pH 4.5, whereas HSV-1 required 60 min for comparable inactivation. Mixtures of TF-3 and LA stored at 37 °C for 1 month at pH 4.0 to 5.7 maintained antiviral activity. Semen, but not cervical vaginal fluid, decreased LA-dependent antiviral activity at pH 4.0, but adding TF-3 to the mixture reduced HSV titers by 4 to 5 log10. These results indicate that a combination microbicide containing TF-3 and LA could reduce HSV transmission.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Department of Developmental Biochemistry, Staten Island, New York, USA. chisi@rcn.com
authors.forename: Charles E
authors.initials: CE
authors.lastname: Isaacs
authors.forename: Weimin
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D005260:Female; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology*; D055101:Semen Analysis; D014621:Vagina / Q000737:chemistry; D014709:Vero Cells; D019562:Viral Load; D038301:Virus Inactivation / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D044946:Biflavonoids; D004338:Drug Combinations; C585473:theaflavin-3,3'-digallate; C056068:theaflavin; D019344:Lactic Acid; D002392:Catechin