PDF(Pubmed)
Abstract：
Flaviviruses are known to cause a variety of diseases in humans in different parts of the world. There are very limited numbers of antivirals to combat flavivirus infection, and therefore new drug targets must be explored. The flavivirus NS2B-NS3 proteases are responsible for the cleavage of the flavivirus polyprotein, which is necessary for productive viral infection and for causing clinical infections; therefore, they are a promising drug target for devising novel drugs against different flaviviruses. This review highlights the structural details of the NS2B-NS3 proteases of different flaviviruses, and also describes potential antiviral drugs that can interfere with the viral protease activity, as determined by various studies. Moreover, optimized in vitro reaction conditions for studying the NS2B-NS3 proteases of different flaviviruses may vary and have been incorporated in this review. The increasing availability of the in silico and crystallographic/structural details of flavivirus NS2B-NS3 proteases in free and drug-bound states can pave the path for the development of promising antiflavivirus drugs to be used in clinics. However, there is a paucity of information available on using animal cells and models for studying flavivirus NS2B-NS3 proteases, as well as on the testing of the antiviral drug efficacy against NS2B-NS3 proteases. Therefore, on the basis of recent studies, an effort has also been made to propose potential cellular and animal models for the study of flavivirus NS2B-NS3 proteases for the purposes of exploring flavivirus pathogenesis and for testing the efficacy of possible drugs targets, in vitro and in vivo.
摘要：
已知黄病毒在世界不同地区的人类中引起多种疾病。对抗黄病毒感染的抗病毒药物数量非常有限，因此必须探索新的药物靶点。黄病毒NS2B-NS3蛋白酶负责黄病毒多蛋白的切割，这是生产性病毒感染和引起临床感染所必需的；因此，它们是设计针对不同黄病毒的新型药物的有希望的药物靶标。这篇综述强调了不同黄病毒NS2B-NS3蛋白酶的结构细节，还描述了可能干扰病毒蛋白酶活性的潜在抗病毒药物，由各种研究确定。此外，用于研究不同黄病毒NS2B-NS3蛋白酶的优化的体外反应条件可能会有所不同，并已纳入本综述。游离和药物结合状态下的黄病毒NS2B-NS3蛋白酶的计算机和晶体学/结构细节的日益增加的可用性可以为开发用于临床的有希望的抗黄病毒药物铺平道路。然而,关于使用动物细胞和模型研究黄病毒NS2B-NS3蛋白酶的信息很少，以及抗病毒药物对NS2B-NS3蛋白酶的疗效测试。因此,根据最近的研究，还努力提出潜在的细胞和动物模型，用于研究黄病毒NS2B-NS3蛋白酶，以探索黄病毒发病机理和测试可能的药物靶标的功效。在体外和体内。
