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Epigallocatechin Gallate Inactivates Clinical Isolates of Herpes Simplex Virus

Departments of Developmental Biochemistry,¹ Developmental Neurobiology, Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314,² Magee-Womens Research Institute School of Pharmacy, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, Pennsylvania 15213,³ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh/Magee-Womens Hospital, 300 Halket Street, Pittsburgh, Pennsylvania 15213⁴

Received 25 June 2007/ Returned for modification 17 September 2007/ Accepted 20 December 2007

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) (molecular weight, 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 type 1 (HSV-1) and HSV-2. EGCG reduced HSV-2 titers by 1,000-fold in 10 to 20 min and reduced HSV-1 titers by the same amount in 30 to 40 min. 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 h prior to infection with HSV-1 and HSV-2, respectively, does not reduce HSV production. Electron microscopic (EM) studies showed that purified virions exposed to EGCG were damaged, and EM immunogold labeling of the envelope glycoproteins gB and gD was significantly reduced following EGCG treatment while capsid protein labeling was unchanged. When purified HSV-1 envelope glycoproteins gB and gD were incubated with EGCG and then examined by sodium dodecyl sulfate-polyacrylamide 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 in the vagina and appears to be a promising candidate for use in a microbicide to reduce HSV transmission.

Published ahead of print on 14 January 2008.