Novel Artemisinin Derivatives for Cytomegalovirus Therapy

用于巨细胞病毒治疗的新型青蒿素衍生物

基本信息

  • 批准号:
    8227951
  • 负责人:
  • 金额:
    $ 41万
  • 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:
    2011-02-15 至 2016-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cytomegalovirus (CMV) infection is common in humans, with seroprevalence rates reaching as high as 90% by adulthood. Although infection is usually asymptomatic in the normal host, CMV causes serious morbidity and mortality in immunocompromised cohorts, including transplant recipients and patients infected with HIV. CMV retinitis is a serious complication in patients with AIDS and profound immunosuppression. In addition, congenital CMV is the leading infectious cause of mental retardation and deafness in the United States. Current CMV therapies are effective in suppressing virus replication, but result in serious side effects, and the emergence of resistant viruses. Development of new compounds could significantly reduce morbidity and mortality from this pathogen. The overall goal of this application is to investigate the anti-CMV activities of artemisinins. Several artemisinin derivatives are widely used in malaria therapy. These compounds are orally available and have a good safety profile. The proposed investigation can be accomplished by our development of anti-viral assays and the availability of newly-synthesized artemisinin derivatives at Johns Hopkins University. We reported recently that dimeric artemisinins are dramatically more effective than the monomeric forms in inhibiting CMV replication in human fibroblasts. We have also shown that inhibition of CMV replication occurs at a very early stage of virus replication. The anti-CMV mechanism of artemisinins may be different than CMV inhibition by currently available compounds. We propose to identify the most potent anti-CMV artemisinin derivative, to evaluate whether combination with approved anti-CMV drugs is additive, and to elucidate mechanisms by which artemisinins inhibit CMV replication. This application is feasible and novel because we have acquired the experience and tools necessary for performing all experiments. For the first time we will use high throughput proteomics to identify the intracellular targets of artemisinins. The information derived from this application will have important impact on CMV therapy. It may lead to new concepts in CMV therapeutics by using a combination of compounds with direct anti-viral target and compounds which target a cellular protein that is important for CMV replication. PUBLIC HEALTH RELEVANCE: Infection with Human Cytomegalovirus (CMV) is endemic, and associated with severe morbidity and mortality in congenitally-infected newborns and immunocompromised hosts. Treatment options for CMV infection are limited, and it is important to develop new therapeutic strategies against CMV. The overall aim of this proposal is to determine the activities and potential mechanisms of artemisinins as anti-CMV drugs.
描述(由申请人提供):巨细胞病毒(CMV)感染在人类中很常见,成年后血清阳性率高达 90%。尽管正常宿主的感染通常是无症状的,但 CMV 会导致免疫功能低下人群(包括移植受者和感染 HIV 的患者)严重发病和死亡。 CMV 视网膜炎是艾滋病和严重免疫抑制患者的严重并发症。此外,先天性巨细胞病毒是美国智力低下和耳聋的主要原因。目前的巨细胞病毒疗法可以有效抑制病毒复制,但会导致严重的副作用以及耐药病毒的出现。新化合物的开发可以显着降低这种病原体的发病率和死亡率。本申请的总体目标是研究青蒿素的抗 CMV 活性。几种青蒿素衍生物广泛用于疟疾治疗。这些化合物可口服,并且具有良好的安全性。拟议的研究可以通过我们在约翰·霍普金斯大学开发的抗病毒检测方法和新合成的青蒿素衍生物来完成。我们最近报道,二聚青蒿素在抑制人成纤维细胞中 CMV 复制方面比单体形式更有效。我们还表明,CMV 复制的抑制发生在病毒复制的早期阶段。青蒿素的抗 CMV 机制可能与目前可用的化合物抑制 CMV 不同。我们建议鉴定最有效的抗 CMV 青蒿素衍生物,评估与已批准的抗 CMV 药物的组合是否具有相加作用,并阐明青蒿素抑制 CMV 复制的机制。该应用程序是可行且新颖的,因为我们已经获得了执行所有实验所需的经验和工具。我们将首次使用高通量蛋白质组学来鉴定青蒿素的细胞内靶标。从该应用中获得的信息将对 CMV 治疗产生重要影响。通过使用具有直接抗病毒靶点的化合物和针对对 CMV 复制重要的细胞蛋白的化合物的组合,它可能会带来 CMV 治疗的新概念。 公共卫生相关性:人类巨细胞病毒 (CMV) 感染是地方性流行病,与先天性感染的新生儿和免疫功能低下宿主的严重发病率和死亡率相关。 CMV 感染的治疗选择有限,开发针对 CMV 的新治疗策略非常重要。该提案的总体目标是确定青蒿素作为抗巨细胞病毒药物的活性和潜在机制。

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 }}

Ravit Boger其他文献

Ravit Boger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('Ravit Boger', 18)}}的其他基金

Autophagy activation – a novel strategy for inhibition of human cytomegalovirus
自噬激活——抑制人类巨细胞病毒的新策略
  • 批准号:
    10442936
  • 财政年份:
    2022
  • 资助金额:
    $ 41万
  • 项目类别:
Autophagy activation – a novel strategy for inhibition of human cytomegalovirus
自噬激活——抑制人类巨细胞病毒的新策略
  • 批准号:
    10615151
  • 财政年份:
    2022
  • 资助金额:
    $ 41万
  • 项目类别:
High Throughput Screening for Identification of Human Cytomegalovirus Inhibitors
用于鉴定人类巨细胞病毒抑制剂的高通量筛选
  • 批准号:
    8870334
  • 财政年份:
    2014
  • 资助金额:
    $ 41万
  • 项目类别:
High Throughput Screening for Identification of Human Cytomegalovirus Inhibitors
用于鉴定人类巨细胞病毒抑制剂的高通量筛选
  • 批准号:
    9056570
  • 财政年份:
    2014
  • 资助金额:
    $ 41万
  • 项目类别:
High Throughput Screening for Identification of Human Cytomegalovirus Inhibitors
用于鉴定人类巨细胞病毒抑制剂的高通量筛选
  • 批准号:
    8756332
  • 财政年份:
    2014
  • 资助金额:
    $ 41万
  • 项目类别:
Novel Artemisinin Derivatives for Cytomegalovirus Therapy
用于巨细胞病毒治疗的新型青蒿素衍生物
  • 批准号:
    8415971
  • 财政年份:
    2011
  • 资助金额:
    $ 41万
  • 项目类别:
Novel Artemisinin Derivatives for Cytomegalovirus Therapy
用于巨细胞病毒治疗的新型青蒿素衍生物
  • 批准号:
    8082274
  • 财政年份:
    2011
  • 资助金额:
    $ 41万
  • 项目类别:
Novel Artemisinin Derivatives for Cytomegalovirus Therapy
用于巨细胞病毒治疗的新型青蒿素衍生物
  • 批准号:
    8795657
  • 财政年份:
    2011
  • 资助金额:
    $ 41万
  • 项目类别:
Novel Artemisinin Derivatives for Cytomegalovirus Therapy
用于巨细胞病毒治疗的新型青蒿素衍生物
  • 批准号:
    8603834
  • 财政年份:
    2011
  • 资助金额:
    $ 41万
  • 项目类别:
CMV-encoded TNF receptor and viral dissemination
CMV 编码的 TNF 受体和病毒传播
  • 批准号:
    7640222
  • 财政年份:
    2009
  • 资助金额:
    $ 41万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 41万
  • 项目类别:
    Research Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 41万
  • 项目类别:
    Standard Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 41万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 41万
  • 项目类别:
    Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 41万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 41万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 41万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了