Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses

Interferon, ribavirin, 6-azauridine and glycyrrhizin: antiviral compounds active against pathogenic flaviviruses
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DOI:
10.1016/s0166-3542(02)00185-7
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发表时间:
2003-03-01
期刊:
影响因子:
7.6
通讯作者:
Garin, D
Garin, D
中科院分区:
医学2区
文献类型:
--
作者:
Crance, JM;Scaramozzino, N;Garin, D

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利巴韦林、干扰素-α (IFN-α)、6-氮杂苷和甘草酸在体外测试了它们对 I1 致病性黄病毒的抗病毒活性,这些黄病毒属于主要抗原复合物或具有医学重要性的单个血清群:登革热、日本脑炎、哺乳动物蜱传病毒和黄热病病毒 (YFV) 群。通过Vero细胞中每种黄病毒的细胞病变效应的降低和病毒滴度的降低来评估抗病毒活性。通过测定汇合细胞培养物中台盼蓝排斥的抑制作用以及评估对细胞生长的抑制作用来评估细胞毒性。通过选择性指数(CC50/EC50)评估每种测试化合物的作用特异性。 IFN-α 被证明是一种选择性且有效的抑制剂,可抑制已测试的致病性黄病毒的复制。利巴韦林和 6-氮杂苷被证明在不改变正常细胞形态的浓度下对 I1 测试的致病性黄病毒的复制具有活性,但由于它们的细胞抑制作用,当评估关于细胞生长抑制的选择性指数时,它们不是选择性抑制剂。甘草甜素在高非细胞毒性浓度下抑制黄病毒的复制。应进一步评估这些抗黄病毒化合物在体内治疗黄病毒感染中的功效。 (C) 2002 Elsevier Science B.V. 保留所有权利。
Ribavirin, interferon-alpha (IFN-alpha), 6-azauridine and glycyrrhizin were tested in vitro for their antiviral activities against I I pathogenic flaviviruses belonging to principal antigenic complexes or individual serogroups of medical importance: dengue, Japanese encephalitis, mammalian tick-borne and yellow fever virus (YFV) groups. Antiviral activity was estimated by the reduction of the cytopathic effect of each flavivirus in Vero cells and by the reduction in virus titer. Cytotoxicity was evaluated by determining the inhibition of Trypan blue exclusion in confluent cell cultures and by the evaluation of the inhibitory effect on cell growth. The specificity of action of each tested compound was estimated by the selectivity index (CC50/EC50). IFN-alpha proved to be a selective and potent inhibitor of the replication of the I I tested pathogenic flaviviruses. Ribavirin and 6-azauridine proved to be active on the replication of the I I tested pathogenic flaviviruses at the concentrations which did not alter normal cell morphology, but they were not selective inhibitors when selectivity indices were evaluated with regard to the inhibition of cell growth because of their cytostatic effect. Glycyrrhizin inhibited the replication of flaviviruses at high non-cytotoxic concentrations. These antiflavivirus compounds should be further evaluated for their efficacy in the treatment of flavivirus infections in vivo. (C) 2002 Elsevier Science B.V. All rights reserved.