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2',3'-二脱氧胞苷对鸭乙型肝炎病毒复制的抑制作用。一种强效逆转录酶抑制剂。

Inhibition of duck hepatitis B virus replication by 2',3'-dideoxycytidine. A potent inhibitor of reverse transcriptase.

作者信息

Kassianides C, Hoofnagle J H, Miller R H, Doo E, Ford H, Broder S, Mitsuya H

机构信息

Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.

出版信息

Gastroenterology. 1989 Nov;97(5):1275-80. doi: 10.1016/0016-5085(89)91699-5.

Abstract

The effect of 2',3'-dideoxycytidine, a potent antiviral agent, which, following anabolic phosphorylation, inhibits the reverse transcriptase of the human immunodeficiency virus in vitro, was assessed in 16 Pekin ducks chronically infected with the duck hepatitis B virus. Nine ducks were given 11 mg/m2 of dideoxycytidine intravenously every 6 h, and 7 ducks received no treatment. Serum duck hepatitis B virus deoxyribonucleic acid and deoxyribonucleic acid polymerase activity decreased in every duck treated with dideoxycytidine. The mean inhibition of deoxyribonucleic acid polymerase and duck hepatitis B virus deoxyribonucleic acid on the third day of treatment measured 64% (p less than 0.01) and 73% (p less than 0.01), respectively. The inhibition of deoxyribonucleic acid polymerase persisted after treatment was stopped, and 4 ducks continued to show greater than 50% inhibition 12 days after stopping treatment. Duck hepatitis B virus deoxyribonucleic acid, which was measured in total cellular deoxyribonucleic acid extracted from liver biopsy specimens obtained before and on the last day of treatment with dideoxycytidine, showed an average inhibition of 96% in 3 ducks treated with dideoxycytidine, but showed no decrease in the remaining 5 ducks. Thus, dideoxycytidine has potent antiviral activity against duck hepatitis B virus and warrants further evaluation as an antiviral agent in the treatment of chronic hepatitis B virus infection in humans.

摘要

2',3'-双脱氧胞苷是一种强效抗病毒药物,经合成代谢磷酸化后,它在体外可抑制人类免疫缺陷病毒的逆转录酶。我们对16只慢性感染鸭乙型肝炎病毒的北京鸭评估了该药物的效果。9只鸭子每6小时静脉注射11mg/m²的双脱氧胞苷,7只鸭子未接受治疗。接受双脱氧胞苷治疗的每只鸭子的血清鸭乙型肝炎病毒脱氧核糖核酸和脱氧核糖核酸聚合酶活性均下降。治疗第三天,脱氧核糖核酸聚合酶和鸭乙型肝炎病毒脱氧核糖核酸的平均抑制率分别为64%(p<0.01)和73%(p<0.01)。停药后,脱氧核糖核酸聚合酶的抑制作用仍然存在,4只鸭子在停药12天后仍表现出超过50%的抑制率。在用双脱氧胞苷治疗前及治疗最后一天从肝活检标本中提取的总细胞脱氧核糖核酸中检测到的鸭乙型肝炎病毒脱氧核糖核酸,在3只接受双脱氧胞苷治疗的鸭子中平均抑制率为96%,但其余5只鸭子未出现下降。因此,双脱氧胞苷对鸭乙型肝炎病毒具有强效抗病毒活性,有必要作为一种抗病毒药物进一步评估其在治疗人类慢性乙型肝炎病毒感染中的作用。

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