Kianse Networks Controling Flavivirus Replication
Kianse Networks 控制黄病毒复制
基本信息
- 批准号:8234067
- 负责人:
- 金额:$ 64.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-03-01 至 2014-02-28
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAntiviral AgentsBiochemicalCell modelCell physiologyCellsChemicalsComputer SimulationDataDengueDengue VirusDrug Delivery SystemsEnvironmentEnzymesFlavivirusFlavivirus InfectionsGene TargetingGenesGenomeGenomicsGoalsGrowthImmune responseIn VitroInfectionInfection ControlJapanese EncephalitisLibrariesLife Cycle StagesMitogen-Activated Protein KinasesModelingMusPacific NorthwestPathway interactionsPharmaceutical ChemistryPhosphorylationPhosphotransferasesProtein BindingProtein KinaseProteinsScreening procedureSignal PathwaySmall Interfering RNASpecificityTestingTherapeuticThioureaTissuesToxic effectTyrosine Kinase InhibitorViralViral PhysiologyVirusVirus DiseasesVirus InhibitorsVirus ReplicationWest Nile virusYellow fever virusanalogbasecell typedrug discoveryfunctional genomicsin vivoindexinginhibitor/antagonistinsightkinase inhibitormouse modelnovelpreventprogramsresearch studysmall moleculesmall molecule librariessrc-Family Kinases
项目摘要
Flaviviruses need and manipulate host cell pathways at every step of their infectious cycle. Since many host
cell pathways are controlled by protein kinases, this class of host proteins is intimately involved in modulating
flaviviral replication both negatively, ie. by controlling innate immune responses, as well as positively, by
inducing a virus-supportive environment. The goal of this sub-project is to identify those kinase-controlled
host cell pathways that support the flavivirus life cycle. Our preliminary data show that broad-spectrum
protein tyrosine kinase inhibitors prevent flaviviral entry whereas MAP-kinase inhibitors interfere with
replication. Moreover, we previously demonstrated that Src-kinase inhibitors block flaviviral egress due to a
requirement of the c-yes kinase for this step. To identify both specific inhibitors and specific kinases
controlling each step of the viral life cycle we will use a chemical genomics approach. We will employ cellbased,
high content screening of kinase-directed small molecule libraries to identify kinase inhibitors
interfering with different steps of the Dengue-virus (DENV) life cycle. In secondary screens we will select for
compounds with a high selectivity index, broad cell type specificity and activity against other flaviviruses
(WNV, JEV, YFV). Active compounds will likely inhibit several related kinases thus minimizing the problem of
redundancy of signaling pathways and tissue specific expression. The kinases targeted by a given
compound will be identified by combining computational, functional genomics and biochemical approaches.
Based on these results we will generate models of kinase networks controlling flavivirus infection and
examine thise models experimentally by phosphoproteomics and by targeted gene knockdown. Finally, we
will examine the therapeutic potential of kinase-targeted antivirally active compounds by examining selected
compounds in vivo using a murine model West-Nile Virus infection. The efficacy, toxicity and bio-availability
of kinase-directed compounds will be compared with the in vivo activity of TYT-1 analogs (sultam thioureas)
generated in sub-project 3 of this program. At the end of these comprehensive studies, we anticipate to have
gained further insights into the interaction of flaviviruses with their host cell, identified novel targets for
antviral drugs discovery, and characterized novel small molecule inhibitors that are active against flaviviruses
in vitro and in vivo.
黄病毒在其感染周期的每一步都需要并操纵宿主细胞通路。既然很多主持人
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Klaus J Fruh其他文献
Klaus J Fruh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('Klaus J Fruh', 18)}}的其他基金
Non-canonical epitope presentation and antigen processing by MHC-E
MHC-E 的非典型表位呈递和抗原加工
- 批准号:
10801509 - 财政年份:2023
- 资助金额:
$ 64.83万 - 项目类别:
A Cytomegalovirus-based Vaccine Targeting the Pre-erythrocytic Stage of Malaria
一种针对疟疾红细胞前阶段的巨细胞病毒疫苗
- 批准号:
9982274 - 财政年份:2017
- 资助金额:
$ 64.83万 - 项目类别:
A Cytomegalovirus-based Vaccine Targeting the Pre-erythrocytic Stage of Malaria
一种针对疟疾红细胞前阶段的巨细胞病毒疫苗
- 批准号:
9238234 - 财政年份:2017
- 资助金额:
$ 64.83万 - 项目类别:
A Cytomegalovirus-based Vaccine Targeting the Pre-erythrocytic Stage of Malaria
一种针对疟疾红细胞前阶段的巨细胞病毒疫苗
- 批准号:
9751633 - 财政年份:2017
- 资助金额:
$ 64.83万 - 项目类别:
An Effector Memory T Cell-Inducing Subunit Vaccine against Malaria
一种针对疟疾的效应记忆 T 细胞诱导亚单位疫苗
- 批准号:
8607501 - 财政年份:2013
- 资助金额:
$ 64.83万 - 项目类别:
An Effector Memory T Cell-Inducing Subunit Vaccine against Malaria
一种针对疟疾的效应记忆 T 细胞诱导亚单位疫苗
- 批准号:
8423271 - 财政年份:2013
- 资助金额:
$ 64.83万 - 项目类别:
MECHANISMS OF IMMUNE VULNERABILITY OF THE ELDERLY TO THE WEST NILE VIRUS
老年人对西尼罗河病毒免疫脆弱的机制
- 批准号:
8357751 - 财政年份:2011
- 资助金额:
$ 64.83万 - 项目类别:
EVASION OF ANTIGEN PRESENTATION BY RHESUS CYTOMEGALOVIRUS
恒河猴巨细胞病毒逃避抗原呈递
- 批准号:
8357750 - 财政年份:2011
- 资助金额:
$ 64.83万 - 项目类别:
MODULATION OF INNATE IMMUNE RESPONSES BY CYTOMEGALOVIRUS
巨细胞病毒对先天免疫反应的调节
- 批准号:
8357775 - 财政年份:2011
- 资助金额:
$ 64.83万 - 项目类别:
Development and Analysis of Replication-Deficient CMV Vectors
复制缺陷型 CMV 载体的开发和分析
- 批准号:
8117930 - 财政年份:2011
- 资助金额:
$ 64.83万 - 项目类别:
相似海外基金
Development of a new generation of antiviral agents that are effective against drug-resistant viruses and prevent serious illness and sequelae.
开发新一代抗病毒药物,可有效对抗耐药病毒并预防严重疾病和后遗症。
- 批准号:
23K18186 - 财政年份:2023
- 资助金额:
$ 64.83万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
A versatile structure-based therapeutic platform for development of VHH-based antitoxin and antiviral agents
一个多功能的基于结构的治疗平台,用于开发基于 VHH 的抗毒素和抗病毒药物
- 批准号:
10560883 - 财政年份:2023
- 资助金额:
$ 64.83万 - 项目类别:
Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents
用于发现新型抗病毒药物的基因编码双环肽库
- 批准号:
10730692 - 财政年份:2021
- 资助金额:
$ 64.83万 - 项目类别:
Design and synthesis of nucleosides to develop antiviral agents and oligonucleotide therapeutics
设计和合成核苷以开发抗病毒药物和寡核苷酸疗法
- 批准号:
21K06459 - 财政年份:2021
- 资助金额:
$ 64.83万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Genetically encoded bicyclic peptide libraries for the discoveryof novel antiviral agents
用于发现新型抗病毒药物的基因编码双环肽库
- 批准号:
10189880 - 财政年份:2021
- 资助金额:
$ 64.83万 - 项目类别:
Computer-aided identification and synthesis of novel broad-spectrum antiviral agents
新型广谱抗病毒药物的计算机辅助鉴定和合成
- 批准号:
2404261 - 财政年份:2020
- 资助金额:
$ 64.83万 - 项目类别:
Studentship
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10222540 - 财政年份:2020
- 资助金额:
$ 64.83万 - 项目类别:
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10669717 - 财政年份:2020
- 资助金额:
$ 64.83万 - 项目类别:
Association between sedentary lifestyle and liver cancer development in hepatitis C patients treated with direct-acting antiviral agents
接受直接抗病毒药物治疗的丙型肝炎患者久坐的生活方式与肝癌发展之间的关系
- 批准号:
20K10713 - 财政年份:2020
- 资助金额:
$ 64.83万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Develop broad-spectrum antiviral agents against COVID-19 based on innate immune response to SARS-CoV-2 infection
基于对 SARS-CoV-2 感染的先天免疫反应,开发针对 COVID-19 的广谱抗病毒药物
- 批准号:
10174522 - 财政年份:2020
- 资助金额:
$ 64.83万 - 项目类别: