Section of Gastroenterology, Department of Medicine, University of Oklahoma Health Sciences Center, VA Medical Center, Mailstop 111H, 921 NE 13th Street, Oklahoma City, OK 73104, USA.
Antiviral Res. 2010 Jun;86(3):241-5. doi: 10.1016/j.antiviral.2010.02.325. Epub 2010 Mar 6.
Statins are 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors used for the treatment of hypercholesterolemia. We report that a particular statin, simvastatin (SIM), exhibits strong in vitro anti-HBV activity. Moreover, a combination of SIM with each of the individual nucleos(t)ide analogues lamivudine (LMV), adefovir (ADV), tenofovir (TEN) and entecavir (ETV), showed synergistic antiviral activity. Combination drug treatments were performed in the HepG2.2.15 cell line. Compound combinations were centered on a mixture designed to deliver approximately equipotent (not necessarily equimolar) concentrations of each agent, based on the ninety percent viral inhibition monotherapy values. SIM interacted favorably with all four licensed anti-HBV nucleos(t)ide analogues, especially at molar ratios that approximate combinations likely to be used clinically. As the relative concentration of SIM was raised to an excess, the overall favorability of the interactions progressively increased. SIM displayed about equal degrees of synergy with ADV and TDF. The highest degree of synergy was observed at the 300:1 combination of SIM with ETV. Interactions with LMV were the least favorable. The in vitro potential shown here may greatly augment anti-HBV therapy clinically.
他汀类药物是 3-羟基-3-甲基戊二酰辅酶 A（HMG CoA）还原酶抑制剂，用于治疗高胆固醇血症。我们报告说，一种特定的他汀类药物，辛伐他汀（SIM），表现出很强的体外抗乙型肝炎病毒（HBV）活性。此外，SIM 与拉米夫定（LMV）、阿德福韦（ADV）、替诺福韦（TEN）和恩替卡韦（ETV）的单个核苷（酸）类似物的组合显示出协同抗病毒活性。联合药物治疗在 HepG2.2.15 细胞系中进行。复方组合以基于每种药物的九十%病毒抑制单药治疗值的等效力（不一定等摩尔）浓度设计的混合物为中心。SIM 与所有四种已批准的抗乙型肝炎病毒核苷（酸）类似物相互作用良好，尤其是在接近临床可能使用的摩尔比时。随着 SIM 的相对浓度升高到过量，相互作用的总体有利程度逐渐增加。SIM 与 ADV 和 TDF 显示出相当程度的协同作用。在 SIM 与 ETV 的 300:1 组合中观察到最高的协同作用。与 LMV 的相互作用最不利。这里显示的体外潜力可能会极大地增强乙型肝炎病毒治疗的临床效果。
