Patick A K, Potts K E
Agouron Pharmaceuticals, Inc., San Diego, California 92121, USA.
Clin Microbiol Rev. 1998 Oct;11(4):614-27. doi: 10.1128/CMR.11.4.614.
Currently, there are a number of approved antiviral agents for use in the treatment of viral infections. However, many instances exist in which the use of a second antiviral agent would be beneficial because it would allow the option of either an alternative or a combination therapeutic approach. Accordingly, virus-encoded proteases have emerged as new targets for antiviral intervention. Molecular studies have indicated that viral proteases play a critical role in the life cycle of many viruses by effecting the cleavage of high-molecular-weight viral polyprotein precursors to yield functional products or by catalyzing the processing of the structural proteins necessary for assembly and morphogenesis of virus particles. This review summarizes some of the important general features of virus-encoded proteases and highlights new advances and/or specific challenges that are associated with the research and development of viral protease inhibitors. Specifically, the viral proteases encoded by the herpesvirus, retrovirus, hepatitis C virus, and human rhinovirus families are discussed.
目前,有多种已获批的抗病毒药物可用于治疗病毒感染。然而,在许多情况下,使用第二种抗病毒药物会有益处,因为这将提供替代疗法或联合治疗方法的选择。因此,病毒编码的蛋白酶已成为抗病毒干预的新靶点。分子研究表明,病毒蛋白酶在许多病毒的生命周期中发挥着关键作用,它们通过切割高分子量的病毒多蛋白前体以产生功能性产物,或者通过催化病毒颗粒组装和形态发生所需的结构蛋白的加工过程来实现这一点。本综述总结了病毒编码蛋白酶的一些重要一般特征,并突出了与病毒蛋白酶抑制剂研发相关的新进展和/或特定挑战。具体而言,讨论了疱疹病毒、逆转录病毒、丙型肝炎病毒和人鼻病毒家族编码的病毒蛋白酶。