COMPARATIVE ACTIVITIES OF SEVERAL NUCLEOSIDE ANALOGS AGAINST DUCK HEPATITIS-B VIRUS INVITRO

被引:66
作者
YOKOTA, T [1 ]
KONNO, K [1 ]
CHONAN, E [1 ]
MOCHIZUKI, S [1 ]
KOJIMA, K [1 ]
SHIGETA, S [1 ]
DECLERCQ, E [1 ]
机构
[1] CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM
关键词
D O I
10.1128/AAC.34.7.1326
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Duck hepatitis B virus (DHBV) replication in primary duck hepatocytes was monitored by examining the synthesis of both DHBV DNA and DHBV core antigen. Several nucleoside analogs which were previously shown to inhibit the replication of DNA viruses (i.e., herpesviruses) and retroviruses were examined for their inhibitory effects on the synthesis of DHBV core antigen in primary duck hepatocytes. (S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine, 2',3'-dideoxyadenosine, and 2',3'-dideoxycytidine inhibited DHBV core antigen synthesis at concentrations that were significantly lower than those found to be toxic to the primary hepatocytes. Of all the compounds tested, (S)-HPMPA showed the lowest 50% effective concentration (0.5 μg/ml). The selectivity index or ratio of the 50% cytotoxic concentration to the 50% effective concentration of (S)-HPMPA was greater than 300. (S)-HPMPA not only inhibited DHBV core antigen but also DHBV DNA synthesis in DHBV-infected hepatocytes.
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收藏
页码:1326 / 1330
页数:5
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