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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 已经付出了巨大的努力来开发针对蚊子传播的黄病毒，例如登革热病毒（DENV），西尼罗河病毒（WNV）和日本脑炎病毒（JEV）。但是，迄今为止，尚无此类抗病毒药物。越来越多的证据表明，这些病毒的外涂层或包膜蛋白所谓的茎区域的特定区域参与病毒的进入和病毒组装。该茎在不同的黄病毒中包含几种高度保守的氨基酸。我们猜想这些高度保守的氨基酸在病毒进入和病毒组装中起重要作用。这项研究的目的是分析DENV的茎区域和其他具有医学重要的黄病毒的新靶标，这将导致抗病毒药的发展。 在AIM 1中，我们将研究高度保守的氨基酸在DENV血清型4的进入和组装中的作用。在AIM 2中，我们将研究损伤的机制在DENV血清型4的进入和组装方面的机制。在AIM 3中，我们将研究高度保守的氨基酸在其他DENV Serotypes和Jev和JEV和JEV和JEV和JEV和JEV的作用。 高度保守氨基酸在病毒组装和进入的角色的表征将导致有关黄素复制的分子机制的新见解。反过来，这种新知识将导致新的抗病毒药物的发展，以减少人类苦难和与DENV和其他黄病毒引起的疾病有关的死亡。