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寻找一种针对病毒感染的选择性疗法。

In search of a selective therapy of viral infections.

机构信息

Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.

出版信息

Antiviral Res. 2010 Jan;85(1):19-24. doi: 10.1016/j.antiviral.2009.10.005. Epub 2009 Oct 21.

Abstract

This article is meant as an introductory chapter to the special issue of Antiviral Research on "Twenty-five years of antiretroviral drug development: progress and prospects", commemorating the first description of azidothymidine (AZT) as an antiretroviral agent. This has prompted me to highlight some of the hallmarks that played an important role in my own search of a selective therapy of viral infections: i.e., the induction of interferon by double-stranded RNA [such as poly(I).poly(C)], allowing the cloning and expression of beta-interferon; the discovery of the reverse transcriptase (RT) (and HIV as a retrovirus depending for its replication on RT), allowing the identification and development of a wide variety of RT inhibitors, nowadays used for the treatment of AIDS; the specificity of herpesvirus inhibitors such as acyclovir and BVDU, in the treatment of HSV and VZV infections; the role of acyclic nucleoside phosphonates (tenofovir, adefovir and cidofovir) in the treatment of HIV, HBV and DNA virus infections; and that of the NNRTIs (leading from TIBO to rilpivirine) as an essential part of the current anti-HIV drug cocktails. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010.

摘要

这篇文章是《抗病毒研究》特刊中“抗逆转录病毒药物研发 25 年:进展与展望”一章的引言,旨在纪念最初描述叠氮胸苷(AZT)作为抗逆转录病毒药物的那篇文章。这促使我强调了一些在我寻找病毒感染选择性治疗方法的过程中发挥重要作用的特点:即双链 RNA(如聚(I).聚(C))诱导干扰素,从而能够克隆和表达β干扰素;发现逆转录酶(RT)(以及依赖 RT 进行复制的 HIV 作为逆转录病毒),从而能够鉴定和开发各种各样的 RT 抑制剂,如今这些抑制剂被用于治疗艾滋病;疱疹病毒抑制剂(如阿昔洛韦和 BVDU)在治疗单纯疱疹病毒和水痘带状疱疹病毒感染方面的特异性;无环核苷膦酸酯(替诺福韦、阿德福韦和更昔洛韦)在治疗 HIV、HBV 和 DNA 病毒感染方面的作用;以及 NNRTIs(从 TIBO 到利匹韦林)作为当前抗 HIV 药物鸡尾酒疗法的重要组成部分。本文是《抗病毒研究》特刊的一部分,该特刊标志着抗逆转录病毒药物发现和开发 25 周年,第 85 卷,第 1 期,2010 年。

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