title: Topical application of polyethylenimine as a candidate for novel prophylactic therapeutics against genital herpes caused by herpes simplex virus.
abstract: Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) cause genital herpes, which can enhance the acquisition of human immunodeficiency virus. The development of anti-HSV agents with novel mechanisms of action is urgently required in the topical therapy of genital herpes. In this study, the in vitro and in vivo anti-HSV effects of Epomin SP-012(®), a highly cationic polyethylenimine, were evaluated. When the in vitro antiviral effects of SP-012 were assessed, this compound showed potent activity against HSV-1 and HSV-2. It inhibited the attachment of HSV-2 to host cells and cell-to-cell spread of infection in a concentration-dependent manner and exerted a virucidal effect. No SP-012-resistant HSV-2 was found when the virus was successively passaged in the presence of SP-012. In a mouse genital herpes model, topically administered SP-012 inhibited the progression of the disease caused by HSV infection. These data illustrate that SP-012 may be a novel class of HSV inhibitor that would be acceptable for long-term topical application.
authors.affiliation: Gradutae School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan, khayashi@pha.u-toyama.ac.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Onoue
authors.forename: Kohei
authors.initials: K
authors.lastname: Sasaki
authors.forename: Jung-Bum
authors.initials: JB
authors.lastname: Lee
authors.forename: Penmetcha K R
authors.initials: PK
authors.lastname: Kumar
authors.forename: Subash C B
authors.initials: SC
authors.lastname: Gopinath
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
authors.forename: Takashi
authors.initials: T
authors.lastname: Kai
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006558:Herpes Genitalis / Q000517:prevention & control*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D011094:Polyethyleneimine / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000891:Anti-Infective Agents, Local; D011094:Polyethyleneimine