Antiviral strategies.
Antiviral strategies.
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DOI：
10.1007/978-3-540-79086-0_1
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发表时间：
2009
影响因子：
--
通讯作者：
Kräusslich HG
中科院分区：
文献类型：
--
作者：
Müller B;Kräusslich HG
病毒是必需的细胞内寄生虫，其复制取决于宿主细胞的途径和功能。因此，很难将病毒特异性功能定义为抗感染治疗的合适靶点。然而，过去 50 年来，在开发有效且特异性的抗病毒药物方面已经取得了重大进展。特别是人类免疫缺陷病毒、丙型肝炎病毒和乙型肝炎病毒，它们会导致影响全世界数百万人的慢性感染，是抗病毒研究的主要焦点。最初，抗病毒药物主要针对病毒特异性酶；最近，已经开发出抑制病毒进入或释放步骤的药物。基于病毒蛋白的结构和功能以及病毒与宿主相互作用的分子机制的信息，药物开发的合理方法已经变得越来越成功。目前在基础研究或临床前研究中探索的新策略包括针对对病毒复制重要的宿主因子的方法、利用先天免疫反应系统以及使用旨在干扰病毒基因表达的基因沉默策略。如今，许多针对各种病毒复制步骤的有效病毒抑制药物已被批准用于治疗重要的病毒性疾病。然而，这些药物的使用受到抗病毒耐药性快速发展的限制，这是当前抗病毒治疗的一个核心问题。
Viruses are obligatory intracellular parasites, whose replication depends on pathways and functions of the host cell. Consequently, it is difficult to define virus-specific functions as suitable targets for anti-infective therapy. However, significant progress has been made in the past 50 years towards the development of effective and specific antivirals. In particular, human immunodeficiency virus, hepatitis C virus, and hepatitis B virus, which cause chronic infections affecting millions of individuals world-wide, are a major focus of antiviral research. Initially, antivirals were mainly directed against virus-specific enzymes; more recently, drugs inhibiting the steps of virus entry or release have been developed. Rational approaches towards drug development, based on information about structure and function of viral proteins and molecular mechanisms of virus-host interactions, have become increasingly successful. Novel strategies currently explored in basic research or preclinical studies include approaches targeting host factors important for virus replication, the exploitation of the innate immune response system as well as the use of gene silencing strategies aimed at interfering with viral gene expression. Today, a number of effective virostatics targeting various viral replication steps are approved for treatment of important viral diseases. However, the use of these drugs is limited by the rapid development of antiviral resistance, which represents a central problem of current antiviral therapy.