P1: STEM REGION OF ENVELOPE PROTEIN OF DENGUE VIRUS AND RE-EMERGING FLAVIVIRUSES

P1：登革热病毒和重新出现的黄病毒包膜蛋白的干区

• 批准号: 8360753
• 负责人: Wei-Kung Wang
• 金额: $ 22.2万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360753
• 关键词: Amino Acids; Antiviral Agents; Area; Cessation of life; Culicidae; Dengue Virus; Development; Disease; Emerging Communicable Diseases; Flavivirus; Funding; Grant; Human; Impairment; Infectious Diseases Research; Japanese Encephalitis Viruses; Japanese encephalitis virus; Knowledge; Lead; Molecular; National Center for Research Resources; Pharmaceutical Preparations; Play; Principal Investigator; Research; Research Infrastructure; Resources; Role; Serotyping; Source; United States National Institutes of Health; Virus; Virus Assembly; West Nile virus; cost; env Gene Products; insight; novel; stem

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Considerable effort has been made to develop drugs against mosquito-borne flaviviruses, such as dengue virus (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV). However, to date no such antiviral drugs are available. Growing evidence suggests that a particular area of the so-called stem region of the outer coating, or envelope protein, of these viruses is involved in virus entry and virus assembly. The stem contains several highly conserved amino acids among different flaviviruses. We conjecture that these highly conserved amino acids play important roles in virus entry and virus assembly. The objective of this study is to analyze the stem region of DENV and other medically important flaviviruses for novel targets that would lead to the development of antiviral drugs. In Aim 1, we will investigate the role of the highly conserved amino acids on the entry and assembly of DENV serotype 4. In Aim 2, we will investigate the mechanisms of impairment on the entry and assembly of DENV serotype 4. And in Aim 3, we will investigate the role of the highly conserved amino acids on the entry and assembly of other DENV serotypes, as well as WNV and JEV. Characterization of the roles of the highly conserved amino acids on virus assembly and entry would lead to new insights about the molecular mechanisms of flavivirus replication. In turn, this new knowledge will lead to the development of new antiviral drugs to reduce the human suffering and deaths associated with diseases caused by DENV and other flaviviruses.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 人们付出了大量努力来开发针对蚊媒黄病毒的药物，例如登革热病毒（DENV）、西尼罗河病毒（WNV）和日本脑炎病毒（JEV）。然而，迄今为止还没有此类抗病毒药物。越来越多的证据表明，这些病毒的外层或包膜蛋白的所谓茎区的特定区域参与病毒进入和病毒组装。茎含有不同黄病毒中几个高度保守的氨基酸。我们推测这些高度保守的氨基酸在病毒进入和病毒组装中发挥重要作用。本研究的目的是分析登革热病毒和其他医学上重要的黄病毒的茎区，寻找新的靶标，从而开发抗病毒药物。 在目标1中，我们将研究高度保守的氨基酸对DENV血清型4的进入和组装的作用。在目标2中，我们将研究对DENV血清型4的进入和组装的损害机制。在目标3中，我们将研究高度保守的氨基酸对其他 DENV 血清型以及 WNV 和 JEV 的进入和组装的作用。 高度保守的氨基酸在病毒组装和进入中的作用的表征将带来关于黄病毒复制分子机制的新见解。反过来，这些新知识将促进新型抗病毒药物的开发，以减少与登革热病毒和其他黄病毒引起的疾病相关的人类痛苦和死亡。