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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- 1)。体外在 Vero细胞内 GA显著抑制 HSV- 1的复制 ,IC50 为0 .0 93μmol/ L,GA对 Vero细胞的毒性 CC50 为 35 0 μmol/ L,治疗指数可达 376 3。HSV- 1腹腔 ( ip)感染 1h后腹腔 ( ip)注射 GA( 0 .0 93～ 0 .37mg/ kg)可以将存活率增加到 6 7%～ 10 0 % ,皮下 ( sc)给药 ( 0 .37mg/ kg)的存活率为 4 3.8% ,都明显高于生理盐水对照组 ( ipP<0 .0 0 1,sc P<0 .0 5 )。GA对小白鼠的急性 L D50 为 15 .5 mg/ kg( ip)。格尔德霉素不影响病毒的吸附、穿入。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
Geldanamycin (GA) is an antibiotic that targets ATP / ADP binding sites on the N-terminus of the heat shock protein Hsp90. In our anti-viral antibiotic screening, geldanamycin was found to be significantly resistant to herpes simplex virus type 1 (HSV-1). GA in Vero cells inhibited the replication of HSV-1 in vitro with an IC50 of 0.93 μmol / L. The cytotoxicity of GA on Vero cells was 35 μmol / L, and the therapeutic index was 376 3. HSV-1 intraperitoneal (ip) infection 1 h after intraperitoneal (ip) injection of GA (0. 93 ~ 0.37mg / kg) can increase the survival rate of 67% ~ 100%, sc .37mg / kg) had a survival rate of 43.8%, which was significantly higher than that of the saline control group (ipP <0 01, sc P <0 05). The acute L D50 of GA in mice was 15.5 mg / kg (ip). Geldanamycin does not affect the adsorption of the virus, penetrate. Because GA inhibits herpes simplex virus type 1 both in vitro and in vivo, GA can be the new drug for herpes simplex virus infections