Melino Sonia, Paci Maurizio
Department of Chemical Science and Technology, University of Rome Tor Vergata, Italy.
FEBS J. 2007 Jun;274(12):2986-3002. doi: 10.1111/j.1742-4658.2007.05831.x. Epub 2007 May 17.
Transmitted by the Aedes aegypti mosquito, the dengue virus is the etiological agent of dengue fever, dengue hemorrhagic fever and dengue shock syndrome, and, as such, is a significant factor in the high death rate found in most tropical and subtropical areas of the world. Dengue diseases are not only a health burden to developing countries, but pose an emerging problem worldwide. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators during dengue disease plays a key role in inducing plasma leakage, shock and hemorrhagic manifestations. Currently, there are no vaccines available against dengue virus, although several tetravalent live-attenuated dengue vaccines are in clinical phases I or II, and prevention through vaccination has become a major priority on the agendas of the World Health Organization and of national ministries of health and military organizations. An alternative to vaccines is found in therapeutic-based approaches. Understanding the molecular mechanisms of viral replication has led to the development of potential drugs, and new molecular viral targets for therapy are emerging. The NS3 protease domain of the NS3 protein is responsible for processing the viral polyprotein and its inhibition is one of the principal aims of pharmacological therapy. This review is an overview of the progress made against dengue virus; in particular, it examines the unique properties--structural and functional--of the NS3 protease for the treatment of dengue virus infections by the inhibition of viral polyprotein processing.
登革病毒通过埃及伊蚊传播，是登革热、登革出血热和登革休克综合征的病原体，因此是世界上大多数热带和亚热带地区高死亡率的一个重要因素。登革热疾病不仅给发展中国家带来健康负担，而且在全球范围内构成一个新出现的问题。免疫病理机制似乎包括一系列复杂的免疫反应。登革热疾病期间细胞因子和化学介质水平的迅速升高在诱导血浆渗漏、休克和出血表现方面起关键作用。目前尚无针对登革病毒的疫苗，尽管几种四价减毒活登革疫苗正处于临床I期或II期，通过接种疫苗进行预防已成为世界卫生组织以及各国卫生部和军事组织议程上的一项主要优先事项。基于治疗的方法是疫苗的一种替代方案。对病毒复制分子机制的了解已促成了潜在药物的开发，并且正在出现新的分子病毒治疗靶点。NS3蛋白的NS3蛋白酶结构域负责处理病毒多聚蛋白，对其进行抑制是药物治疗的主要目标之一。本综述概述了针对登革病毒所取得的进展；特别是，它研究了NS3蛋白酶的独特性质——结构和功能——通过抑制病毒多聚蛋白加工来治疗登革病毒感染。
