Geldanamycin, a ligand of heat shock protein 90, inhibits herpes simplex virus type 2 replication both in vitro and in vivo.
Previously, we discovered geldanamycin, a ligand of heat shock protein 90, effectively inhibited herpes simplex virus type 1 replication in vitro and in vivo (mouse encephalitis model). In this study, we demonstrate that geldanamycin has very strong activities against herpes simplex virus type 2 in vitro and in vivo (mouse vagina model). In mouse vagina model, administration of geldanamycin suspension to vagina after virus infection protected the infected mice from death and increased the average survival days in a dose-dependent manner. Geldanamycin also significantly reduced virus shedding from mouse vagina. All geldanamycin-treated groups were statistically significant when compared with the infected control group. The high-dose group of geldanamycin (5.72 mg kg(-1)) was better than acyclovir group (2.86 mg kg(-1)). All geldanamycin vaginal administration mock-infected groups did not show significant body weight loss. Although geldanamycin has strong antiviral activities against various DNA and RNA viruses, geldanamycin is not suitable for systemic administration because of its high toxicity. We consider that geldanamycin is a candidate of topical usage for the treatment of herpes simplex virus type infections.
Department of Virology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China. yuhuanlibj@126.com
Yu-Huan
YH
Li
Qiao-Ni
QN
Lu
Hui-Qiang
HQ
Wang
Pei-Zhen
PZ
Tao
Jian-Dong
JD
Jiang
D000282:Administration, Intravaginal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D016227:Benzoquinones / Q000008:administration & dosage* / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000502:physiology; D047029:Lactams, Macrocyclic / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D016019:Survival Analysis; D016896:Treatment Outcome; D014621:Vagina / Q000821:virology; D014779:Virus Replication / Q000187:drug effects*; D017201:Virus Shedding
D000998:Antiviral Agents; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; C001277:geldanamycin