Epigallocatechin Gallate Inactivates Clinical Isolates of Herpes Simplex Virus

Departments of Developmental Biochemistry and Developmental Neurobiology, Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314; Magee-Womens Research Institute School of Pharmacy, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA 15213; University of Pittsburgh/Magee-Womens Hospital, Department of Obstetrics, Gynecology & Reproductive Sciences, 300 Halket Street, Pittsburgh, PA 15213

	Abstract

In the absence of a fully effective herpes simplex virus (HSV) vaccine, topical microbicides represent an important strategy for preventing HSV transmission. (-) Epigallocatechin gallate (EGCG) (MW 458.4) is the primary catechin in green tea. The present study shows that EGCG has greater anti-HSV activity than other green tea catechins and inactivates multiple clinical isolates of HSV-1 and HSV-2. EGCG reduced HSV-2 titers by 1,000-fold in 10-20 minutes and reduced HSV-1 titers by the same amount in 30 – 40 minutes. The anti-HSV activity of EGCG is due to a direct effect on the virion and incubating Vero and CV1 cells with EGCG for 48 hours prior to infection with HSV-1 and HSV-2 respectively does not reduce HSV production. Electron microscopical (EM) studies showed that purified virions exposed to EGCG were damaged and EM immunogold labelling of the envelope glycoproteins gB and gD was significantly reduced following EGCG treatment while capsid protein labelling was unchanged. When the purified HSV-1 envelope glycoproteins gB and gD were incubated with EGCG and then examined by SDS gel electrophoresis, lower molecular weight gB and gD bands decreased and new higher molecular weight bands appeared indicating the EGCG dependent production of macromolecular complexes. gB and gD are essential for HSV infectivity and these results suggest that EGCG could inactivate HSV virions by binding to gB, gD or another envelope glycoprotein. EGCG is stable in the pH range found vaginally and appears to be a promising candidate for use in a microbicide to reduce HSV transmission.