Proteases and protease inhibitors in infectious diseases

被引:141
作者
Agbowuro, Ayodeji A. [1 ]
Huston, Wilhelmina M. [2 ]
Gamble, Allan B. [1 ]
Tyndall, Joel D. A. [1 ]
机构
[1] Univ Otago, Sch Pharm, POB 56, Dunedin 9054, New Zealand
[2] Univ Technol Sydney, Sch Life Sci, Ultimo, NSW, Australia
关键词
infectious disease; protease; protease inhibitors; ATP-DEPENDENT PROTEASE; VIRUS NS3/4A PROTEASE; TREATMENT-EXPERIENCED PATIENTS; SECRETED ASPARTYL PROTEINASES; STRUCTURE-BASED DESIGN; CRYSTAL-STRUCTURE; SERINE-PROTEASE; HIV-1; PROTEASE; ACTIVE-SITE; CYSTEINE PROTEASE;
D O I
10.1002/med.21475
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3-4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy. A significant aspect of this review discusses the chemical and pharmacological characteristics of inhibitors of the various proteases discussed. A total of 25 inhibitors have been considered potent and safe enough to be trialed in humans and are at different levels of clinical application. We assess the mechanism of action and clinical performance of the protease inhibitors against infectious agents with their developmental strategies and look to the next frontiers in the use of protease inhibitors as anti-infective agents.
引用
收藏
页码:1295 / 1331
页数:37
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