Function and mechanism of the HCV p7 channel and its therapeutic potential
HCV p7通道的功能、机制及其治疗潜力
基本信息
- 批准号:8880443
- 负责人:
- 金额:$ 50.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-15 至 2016-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdamantaneAddressAffectArchitectureBindingBinding SitesBiological AssayBiophysicsCapsidCationsCellsCommunitiesComplexDevelopmentDivalent CationsDrug InteractionsElementsEnvironmentEukaryotaFutureGenomeGenotypeHealthHepatitis CHepatitis C virusHepatitis C virus p7 proteinIn VitroInfluenzaInvestigationIonsKnowledgeLife Cycle StagesLipidsLiposomesLiver diseasesMediatingMembraneMethodsMolecular VirologyMutationNaturePermeabilityPharmaceutical ChemistryProcessProductionProkaryotic CellsProteinsRNAReadingReportingResearchRoleSolutionsStructureTestingTherapeuticTitrationsVaccinesViralVirionVirusVirus Assemblyanti-hepatitis Cbasedrug developmentextracellularin vivoinhibitor/antagonistinterdisciplinary approachmutantnovelnovel strategiespatch clampprotein protein interactionresearch studysmall moleculesolid state nuclear magnetic resonancevirology
项目摘要
DESCRIPTION (provided by applicant): This proposal aims to investigate the function and therapeutic potential of the viroporin protein, p7, of Hepatitis C virus (HCV) using a combination of structural and functional approaches. The p7 protein encoded by the HCV genome is required for viral replication; it has been shown to facilitate efficient assembly and release of infectious virions. In membrane, p7 forms a cation-selective channel. The structure of the p7 channel solved recently in our lab shows a novel architecture developed by the virus to conduct cations across the membrane. The structure also revealed channel elements that partially resemble those of known Ca2+/Mg2+ channels, which provide clues for further research to understand channel mechanism. Like most viroporins, the function of p7-mediated cation conduction during viral assemble and release remains elusive. The fact that p7 forms a well-defined channel structure suggests a role of ion permeability in these processes, and urges new investigations to better define this role. The p7 channel has also been pursued as an anti-HCV target because blocking the channel activity reduced production of infectious viral progeny. Several compounds have already been shown to inhibit channel activity, including the adamantane derivatives that also block the influenza M2 channel. These drug interactions could provide useful information for rational drug development, but how and where do these compounds act on the p7 channel are unknown. We propose to employ multidisciplinary approaches in biophysics, molecular virology, and medicinal chemistry to investigate the mechanism of cation conduction, the effect of channel activity in virus assembly and release, and the structural bases of channel inhibition by the known inhibitors. The knowledge to be gained from the proposed research may give rise to new opportunities for developing compounds for treating HCV infections.
描述(由申请人提供):本提案旨在使用结构和功能方法的组合研究丙型肝炎病毒(HCV)的病毒孔蛋白p7的功能和治疗潜力。由HCV基因组编码的p7蛋白是病毒复制所需的;它已被证明有助于感染性病毒体的有效组装和释放。在膜中,p7形成阳离子选择性通道。我们实验室最近解决的p7通道的结构显示了病毒开发的一种新结构,可以通过膜传导阳离子。该结构还揭示了部分类似于已知Ca 2 +/Mg 2+通道的通道元件,这为进一步研究通道机制提供了线索。像大多数病毒孔蛋白一样,在病毒组装和释放期间p7介导的阳离子传导的功能仍然难以捉摸。事实上,p7形成了一个明确的通道结构,表明在这些过程中的离子渗透性的作用,并敦促新的调查,以更好地确定这一作用。p7通道也被用作抗HCV靶点,因为阻断通道活性减少了感染性病毒后代的产生。几种化合物已经显示出抑制通道活性,包括也阻断流感M2通道的金刚烷衍生物。这些药物相互作用可以为合理的药物开发提供有用的信息,但这些化合物如何以及在何处作用于p7通道尚不清楚。我们建议采用生物物理学,分子病毒学和药物化学多学科的方法来研究阳离子传导的机制,在病毒组装和释放的通道活性的影响,和已知的抑制剂抑制通道的结构基础。从拟议的研究中获得的知识可能会为开发治疗HCV感染的化合物带来新的机会。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Genotype-specific differences in structural features of hepatitis C virus (HCV) p7 membrane protein.
基因型特异性丙型肝炎病毒(HCV)P7膜蛋白的特异性差异。
- DOI:10.1016/j.bbamem.2015.03.006
- 发表时间:2015-06
- 期刊:
- 影响因子:0
- 作者:Kalita MM;Griffin S;Chou JJ;Fischer WB
- 通讯作者:Fischer WB
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JAMES Jeiwen CHOU其他文献
JAMES Jeiwen CHOU的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JAMES Jeiwen CHOU', 18)}}的其他基金
Structural and Functional Roles of the Membrane-Related Components of Single-Pass Membrane Proteins
单程膜蛋白膜相关成分的结构和功能作用
- 批准号:
10380877 - 财政年份:2021
- 资助金额:
$ 50.76万 - 项目类别:
CONTROL AND ACTIVATION OF THE TUMOR NECROSIS FACTOR RECEPTORS
肿瘤坏死因子受体的控制和激活
- 批准号:
10338106 - 财政年份:2020
- 资助金额:
$ 50.76万 - 项目类别:
CONTROL AND ACTIVATION OF THE TUMOR NECROSIS FACTOR RECEPTORS
肿瘤坏死因子受体的控制和激活
- 批准号:
10092951 - 财政年份:2020
- 资助金额:
$ 50.76万 - 项目类别:
Structure-function studies of the membrane-interacting domains of HIV-1 Env spike
HIV-1 Env 刺突膜相互作用域的结构功能研究
- 批准号:
10326632 - 财政年份:2016
- 资助金额:
$ 50.76万 - 项目类别:
Structure-function studies of the membrane-interacting domains of HIV-1 Env spike
HIV-1 Env 刺突膜相互作用域的结构功能研究
- 批准号:
9203214 - 财政年份:2016
- 资助金额:
$ 50.76万 - 项目类别:
Structure-function studies of the membrane-interacting domains of HIV-1 Env spike
HIV-1 Env 刺突膜相互作用域的结构功能研究
- 批准号:
9275921 - 财政年份:2016
- 资助金额:
$ 50.76万 - 项目类别:
Structure-function studies of the membrane-interacting domains of HIV-1 Env spike
HIV-1 Env 刺突膜相互作用域的结构功能研究
- 批准号:
9899171 - 财政年份:2016
- 资助金额:
$ 50.76万 - 项目类别:
Function and mechanism of the HCV p7 channel and its therapeutic potential
HCV p7通道的功能、机制及其治疗潜力
- 批准号:
9198039 - 财政年份:2016
- 资助金额:
$ 50.76万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 50.76万 - 项目类别:
Research Grant