Sherker A H, Hirota K, Omata M, Okuda K
Gastroenterology. 1986 Oct;91(4):818-24. doi: 10.1016/0016-5085(86)90681-5.
Foscarnet (trisodium phosphonoformate) is a new antiviral compound with in vitro inhibitory effects against the DNA polymerases of hepadna viruses. To study the effects of the drug in chronic hepadna virus infection, we treated ducks chronically infected with duck hepatitis B virus for 10 days with either low-dose foscarnet (50 mg/kg i.p. b.i.d.), high-dose foscarnet (250 mg/kg i.p. b.i.d.), or sterile water injections. Serum duck hepatitis B virus DNA and intrahepatic replicative forms of the virus were measured using molecular biological techniques with both a double-stranded radiolabeled DNA probe and a plus-strand (noncoding) specific RNA probe. We found a dose-related decrease in serum and intrahepatic duck hepatitis B virus DNA during treatment, with a rapid return toward baseline values after the cessation of treatment. There was a disproportionate decrease in the plus strand of viral DNA with treatment. We conclude that foscarnet exerts its effect in hepadna virus infection through inhibition of viral DNA polymerase. Further study is necessary to determine whether foscarnet, by itself or in combination with other treatment modalities, has a role to play in the treatment of chronic hepatitis B infections in humans.
膦甲酸(膦甲酸钠三钠)是一种新型抗病毒化合物,对嗜肝DNA病毒的DNA聚合酶具有体外抑制作用。为研究该药物在慢性嗜肝DNA病毒感染中的作用,我们用低剂量膦甲酸(50毫克/千克腹腔注射,每日两次)、高剂量膦甲酸(250毫克/千克腹腔注射,每日两次)或无菌水注射对慢性感染鸭乙型肝炎病毒的鸭子进行了10天的治疗。使用分子生物学技术,采用双链放射性标记DNA探针和正链(非编码)特异性RNA探针,检测血清鸭乙型肝炎病毒DNA和肝内病毒复制形式。我们发现治疗期间血清和肝内鸭乙型肝炎病毒DNA呈剂量相关下降,治疗停止后迅速恢复至基线值。治疗后病毒DNA正链下降不成比例。我们得出结论,膦甲酸通过抑制病毒DNA聚合酶在嗜肝DNA病毒感染中发挥作用。有必要进一步研究膦甲酸单独或与其他治疗方式联合使用在人类慢性乙型肝炎感染治疗中是否起作用。