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

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.