title: [Shizukaol F: a new structural type inhibitor of HIV-1 reverse transcriptase RNase H].
abstract: 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 micromol x L(-1). This result is consistent with its inhibitory effect on HIV-1 replication (IC50 of 6.12 micromol x L(-1)). Mechanism studies showed that compound shizukaol F inhibited HIV-1 RT-RNase H with IC50 of 26.4 micromol x 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.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Ying-li
authors.initials: YL
authors.lastname: Cao
authors.forename: Hai-yang
authors.initials: HY
authors.lastname: Liu
authors.forename: Huan
authors.initials: H
authors.lastname: Yan
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
mesh_terms: D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D057809:HEK293 Cells; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D019684:Magnoliopsida / Q000737:chemistry*; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016914:Ribonuclease H / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D018894:Reverse Transcriptase Inhibitors; D012717:Sesquiterpenes; C583587:shizukaol F; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H