Geldanamycin (GA) is an antibiotic with its primary target on the ADP/ATP binding site of heat shock protein 90 (Hsp90). In screening for anti-viral candidates from antibiotics we found GA active against HSV-1. GA significantly inhinbited HSV-1 replication in Vero cells. IC5o of GA was 0. 093μmol/L and CC50 of GA was 350μmol/L, resulting in a therapeutic index of 3763. GA administration one hour after HSV-I infection (ip) protected the infected mice from death, in which ip injection (0. 093～0. 37mg/kg)induced an increased survival rate of between 67 and 100%, and sc administration (0. 037mg/kg) 43.8%,significantly higher than that of solvent controls (P＜0.001 for ip injection and P＜0. 05 for sc injection).LD50 of GA in the mice was 15.5mg/kg (ip). GA had no effect on viral adsorption and penetration. Since GA inhibits HSV-1 in vitro and in vivo, we considered it as a new drug candidate for HSV-1 infection.%格尔德霉素(GA)是一种抗生素,它的作用靶点是热休克蛋白Hsp90 N末端的ATP/ADP结合位点.在我们对抗病毒的抗生素筛选中,发现格尔德霉素显著抗单纯疱疹病毒1型(HSV一1).体外在Vero细胞内GA显著抑制HSv-1的复制,IC50为0,093μmol/L,GA对Vero细胞的毒性CC50为350μmol/L,治疗指数可达3763.HSV-1腹腔(ip)感染1h后腹腔(ip)注射GA(0.093～0.37mg/kg)可以将存活率增加到67%～100%,皮下(sc)给药(0.37mg/kg)的存活率为43.8%,都明显高于生理盐水对照组(ipP＜0.001.scP＜0.05).GA对小白鼠的急性LD50为15.5mg/kg(ip).格尔德霉素不影响病毒的吸附、穿人.由于GA在体内外都能抑制单纯疱疹病毒1型,GA可以成为新的抗单纯疱疹病毒感染的药物.
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