银线草醇F：一种新结构类型HIV-1逆转录酶RNaseH活性抑制剂

Shizukaol F:a new structural type inhibitor of HIV-1 reverse transcriptase RNase H

乌药烷型二聚倍半萜类化合物银线草醇F具有抑制HIV-1复制活性,为研究该化合物的作用机制,应用实时荧光定量PCR法、ELISA法及荧光测定法分别测定化合物对HIV-1逆转录进程、逆转录酶RNA-依赖DNA聚合酶活性以及RNase H活性的影响。结果显示,银线草醇F抑制HIV-1逆转录产物LTR/Gag生成,IC50为9.11μmol·L 1,与HIV-1活病毒感染实验结果 (6.12μmol·L 1)一致;该化合物特异性抑制RNase H的活性,IC50为26.4μmol·L 1;对逆转录酶的RNA-依赖DNA聚合酶活性无显著影响。银线草醇F是一个作用于RNase H的具有新结构类型的HIV-1逆转录酶抑制剂。

This study is to investigate the mechanism of action of lindenane disesquiterpenoid shizukaol F on HIV-1 replication.Real time quantity PCR,ELISA assay and fluorescence methods were used to test HIV-1 reverse transcription process,RNA-dependent DNA polymerase activity,and RNase H activity,respectively.It showed that shizukaol F inhibited LTR/Gag production of HIV-1 reverse transcription with an IC50 of 9.11 μmol·L？1.This result is consistent with its inhibitory effect on HIV-1 replication（IC50 of 6.12 μmol·L？1）.Mechanism studies showed that compound shizukaol F inhibited HIV-1 RT-RNase H with IC50 of 26.4 μmol·L？1,but had no effect on HIV-1 RT RNA-dependent DNA polymerase activity.In conclusion,shizukaol F is a new structural type HIV-1 RNase H inhibitor.This discovery will provide a clue for new type of reverse transcriptase inhibitors development.