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29楼
发表于 2002-1-3 13:59
Re:20年不懈对乙肝研究终于开花结果
谢谢liver411 兄 总是给我们大家提供很好的消息.
论坛上懂英文的朋友有空请多去英文论坛
(HBV English,里面liver411版主经常转贴一些他精选出来的乙肝方面的国外的好文章.)看看. 参与讨论
方便的话,翻译一些好文章到中文论坛上来.
大家一起出力,能使论坛更好.
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谢谢liver411 兄 在新年的第一天提供了这么好的消息.
和 谢谢特深沉 的翻译.
这种抗病毒药 原理类似拉米夫丁.而且安全性好. 作用效果好.
我们的未来充满希望.
下面是一篇国外科学杂志的报道的文摘.
2001;12月 的抗病毒化学药物杂志发表
作者就是开发这家药物的公司.
大意是, 这种药(LdC,LdT,LdA)能够特异的(表现在不抑制其他15种别的病毒的复制)抑制乙肝病毒的复制,不影响人体DNA的正常复制。在旱獭慢性乙肝动物模型中,每天一次口服能够有效的降低病毒滴度到10的8次放。 并能相应的降低表面抗原。这一类药表现出极好的安全性。其中一种LdT已经进入临床试验。
LdC即将进入临床试验。
这类药物的组合使用将会达到很强的抑制病毒以及缩小耐药性的产生。
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Antivir Chem Chemother 2001;12 Suppl 1:119-29
Antiviral beta-L-nucleosides specific for hepatitis B virus infection.
Novirio Pharmaceuticals, Cambridge, Mass, USA. [email protected]
[Medline record in process]
Three simple, related nucleosides, beta-L-2'-deoxycytidine (LdC), beta-Lthymidine (LdT), and beta-L-2'-deoxyadenosine (LdA), have been discovered to be potent, specific and selective inhibitors of the replication hepatitis B virus (HBV), as well as the closely related duck and woodchuck hepatitis viruses (WHV). Structure-activity relationship analysis indicates that the 3'-OH group of the beta-L-2'-deoxyribose of the beta-L-2'-deoxynucleoside confers specific anti-hepadnavirus activity. The simple nucleosides had no effect on the replication of 15 other RNA and DNA viruses, and did not inhibit human DNA polymerases (alpha, beta and gamma) or compromise mitochondrial function. The nucleosides are efficiently converted intracellularly into active triphosphate metabolites that have a long half-life. Once-daily oral administration of these compounds in the woodchuck efficacy model of chronic HBV infection reduced viral load by as much as 10(8) genome equivalents/ml serum and there was no drug-related toxicity. In addition, a decline in WHV surface antigen (WHsAg) paralleled the decrease in viral load. This class of nucleosides displays an excellent overall safety profile. The first compound, LdT, has already entered clinical trials and LdC, currently being developed as a prodrug, is expected to enter the clinic in the near future. These compounds have the potential for use in combination therapy with the goal of achieving superior viral suppression and diminishing the onset of resistance.
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