格尔德霉素体内外抑制单纯疱疹病毒1型的复制(英文)

Inhibition of herpeslex virus type 1 infection in vitro and in vivo by geldanamycin

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 。

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. IC 50 of GA was 0.093μmol/L and CC 50 of GA was 350μmol/L, resulting in a therapeutic index of 3763. GA administration one hour after HSV 1 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). LD 50 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.