Targeting polyamines to suppress SARS-CoV-2 related disease
靶向多胺抑制 SARS-CoV-2 相关疾病
基本信息
- 批准号:10320073
- 负责人:
- 金额:$ 30.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVACE2Acute Respiratory Distress SyndromeAffectAngiotensin ReceptorAnimal ModelAnimalsAntiviral ResponseApoptosisAutoimmune ResponsesAutophagocytosisBindingCOVID-19COVID-19 pandemicCOVID-19 patientCOVID-19 severityCOVID-19 treatmentCationsCell Culture TechniquesCell ProliferationCell modelCell physiologyCellsClinicalClinical TrialsCollaborationsCommunicable DiseasesCoronavirusDL-alpha-DifluoromethylornithineDiarrheaDiseaseDisease OutbreaksDoseDrug CombinationsEflornithineEndoplasmic ReticulumEnzymesEpithelial CellsEukaryotic CellEvaluationExcretory functionFDA approvedGene ExpressionGenesGenetic TranscriptionGoalsGrowth and Development functionIn VitroIndividualInfectionInflammationInflammatoryInvestigationLeadLife Cycle StagesLower Respiratory Tract InfectionMetabolicMetabolismMiddle East Respiratory Syndrome CoronavirusModelingMusNamesNon-Steroidal Anti-Inflammatory AgentsOrganOrnithine DecarboxylasePathogenesisPathogenicityPathway interactionsPatientsPharmaceutical PreparationsPharmacologic SubstancePharmacologyPhase II Clinical TrialsPlayPolyamine CatabolismPolyaminesPreparationPreventionPrevention approachProkaryotic CellsResearchRoleSARS coronavirusSARS-CoV-2 infectionSARS-CoV-2 pathogenesisSafetySeveritiesSulindacTestingTherapeuticViralViral ProteinsVirusVirus DiseasesVirus ReplicationWorkadenomaanti-viral efficacybasecancer preventioncarcinogenesiscellular targetingcolon cancer preventioncytokinedisorder later incidence preventiondisorder preventiondrug developmentefficacy testingendoplasmic reticulum stressextracellulargastrointestinal systemhigh riskin vivoinhibitormouse modelneutrophilnovelnovel strategiespathogenic virusprotein expressionreceptor expressionrespiratoryresponsestool sampletranslational goaltreatment strategy
项目摘要
ABSTRACT
The pandemic COronaVIrus disease 2019 (COVID-19) is an infectious disease, which is caused by a novel and
highly pathogenic virus strain SARS-CoV-2 (Severe acute respiratory virus syndrome coronavirus 2). The
infection may cause severe lower respiratory tract infection with acute respiratory distress and extrapulmonary
organ disfunctions in infected individuals. Treatment strategy that both limits SARS-CoV-2 replication and reduce
inflammation associated with COVID-19 would provide the greatest therapeutic benefit.
Polyamines are naturally occurring organic cations that are essential for growth and development of both
prokaryotic and eukaryotic cells. Many viruses require host polyamines for replication in the infected cells and
targeting polyamine metabolism during viral infection showed promising results in in vitro and in vivo animal
studies. The goal of this proposal is to test the applicability of two currently FDA approved drugs, eflornithine
(other name α-difluoromethylornithine or DFMO) and sulindac, and their combination for prevention or treatment
of COVID-19 disease. Eftornithine is an irreversible inhibitor of a key polyamine biosynthetic enzyme ornithine
decarboxylase (ODC). Sulindac is a common non-steroidal anti-inflammatory drug (NSAIDs), which also induces
polyamine catabolism. Eflornithine and sulindac work in a complementary manner to reduce intracellular
polyamine levels. The safety doses of eflornithine/sulindac combination have been established for prevention of
recurrence of high-risk adenomas (ClinicalTrials.gov Identifier NCT00118365).
In this proposal we will test the hypothesis that eflornithine and sulindac combination will reduce both the
intracellular polyamine availability for coronavirus replication, and inflammation associated with COVID-19. We
will test this hypothesis using cell culture models (Specific Aim 1) and mouse models of COVID-19 disease
(Specific Aim 2). Planning activities in preparation for clinical trials for eflornithine/sulindac combination for
antiviral indication in collaboration with Cancer Prevention Pharmaceuticals (CPP) (www.canprevent.com) are
also included.
The translational goal of this project is to develop the effective approach for prevention COVID-19 infection
as well as decreasing severity of the viral infection in the COVID-19 patients. It is essential to develop
new approaches to prevention and treatment of virus outbreaks.
摘要
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 }}
DAVID G BESSELSEN其他文献
DAVID G BESSELSEN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('DAVID G BESSELSEN', 18)}}的其他基金
Targeting polyamines to suppress SARS-CoV-2 related disease
靶向多胺抑制 SARS-CoV-2 相关疾病
- 批准号:
10202992 - 财政年份:2021
- 资助金额:
$ 30.7万 - 项目类别:
Autoclave Improvements for UA Animal Facilities
UA 动物设施的高压灭菌器改进
- 批准号:
8712089 - 财政年份:2014
- 资助金额:
$ 30.7万 - 项目类别:
College of Medicine Phoenix Campus Vivarium Phase I Construction
医学院凤凰城校区动物园一期建设
- 批准号:
7898290 - 财政年份:2010
- 资助金额:
$ 30.7万 - 项目类别:
5 NUCLEASE ASSAYS FOR RODENT HEALTH MONITORING
用于啮齿动物健康监测的 5 种核酸酶测定
- 批准号:
2839489 - 财政年份:1999
- 资助金额:
$ 30.7万 - 项目类别:
相似国自然基金
新型蝙蝠MERS簇冠状病毒HKU5的ACE2细胞受体识别及其分子机制研究
- 批准号:
- 批准年份:2024
- 资助金额:0.0 万元
- 项目类别:省市级项目
铁皮石斛通过肠道 ACE2 修复 Trp/GPR142 介
导“肠-胰岛 ”轴血糖调控功能的降糖机制研
究
- 批准号:Y24H280055
- 批准年份:2024
- 资助金额:0.0 万元
- 项目类别:省市级项目
人类ACE2变构抑制剂的成药性及其抗广谱冠状病毒感染的机制研究
- 批准号:82330111
- 批准年份:2023
- 资助金额:220 万元
- 项目类别:重点项目
CAFs来源的外泌体负性调控ACE2促进肾透明细胞癌癌栓新辅助靶向耐药的机制研究
- 批准号:82373169
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
新型蝙蝠MERS簇冠状病毒HKU5的ACE2受体识别及细胞入侵机制研究
- 批准号:32300137
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
基于AT2/ACE2/Ang(1-7)/MAS轴调控心脏-血管-血液系统性重构演变规律研究心衰气虚血瘀证及其益气通脉活血化瘀治法生物学基础
- 批准号:82305216
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
基于外泌体miRNAs介导细胞通讯的大豆ACE2激活肽调控血管稳态机制研究
- 批准号:32302080
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
感毒清经ACE2/Ang(1-7)/MasR信号通路抑制PM2.5诱导慢性气道炎症的机制:聚焦肺泡巨噬细胞极化与“胞葬”的表型串扰
- 批准号:82305171
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
刺参自溶引发机制中ACE2调控靶点的调控网络研究
- 批准号:32372399
- 批准年份:2023
- 资助金额:50 万元
- 项目类别:面上项目
Spike变异对新冠病毒抗原性及ACE2种属嗜性的影响研究
- 批准号:82272305
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
相似海外基金
新型コロナウイルス感染阻害能を有する抗ACE2抗体の阻害機構に関する構造基盤解明
阐明具有抑制新型冠状病毒感染能力的抗ACE2抗体抑制机制的结构基础
- 批准号:
24K09338 - 财政年份:2024
- 资助金额:
$ 30.7万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
ACE2のユビキチン化を介したコロナウイルス感染機構の解明と創薬への挑戦
通过ACE2泛素化阐明冠状病毒感染机制和药物发现的挑战
- 批准号:
22KJ2499 - 财政年份:2023
- 资助金额:
$ 30.7万 - 项目类别:
Grant-in-Aid for JSPS Fellows
ACE2阻害薬およびERK経路阻害薬による慢性腎炎進展抑制効果の検証
ACE2抑制剂和ERK通路抑制剂抑制慢性肾炎进展的效果验证
- 批准号:
23K14982 - 财政年份:2023
- 资助金额:
$ 30.7万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Large-scale compatibility assessments between ACE2 proteins and diverse sarbecovirus spikes
ACE2 蛋白和多种 sarbecovirus 尖峰之间的大规模兼容性评估
- 批准号:
10722852 - 财政年份:2023
- 资助金额:
$ 30.7万 - 项目类别:
一次線毛とコロナウイルス感染におけるACE2の役割の解明
阐明 ACE2 在原发菌毛和冠状病毒感染中的作用
- 批准号:
22KF0004 - 财政年份:2023
- 资助金额:
$ 30.7万 - 项目类别:
Grant-in-Aid for JSPS Fellows
The regulatory roles of ACE2 and its interaction with Nrf2 in arsenic-induced endothelial dysfunction in experimental and epidemiological studies
实验和流行病学研究中 ACE2 的调节作用及其与 Nrf2 的相互作用在砷诱导的内皮功能障碍中的作用
- 批准号:
23K16310 - 财政年份:2023
- 资助金额:
$ 30.7万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Role of ACE2 in the mechanism of intestinal regeneration
ACE2在肠道再生机制中的作用
- 批准号:
23K15078 - 财政年份:2023
- 资助金额:
$ 30.7万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Research and development of a novel pediatric anti-obesity medicine via ACE2 activation in DIZE
通过 DIZE 中 ACE2 激活研发新型儿科抗肥胖药物
- 批准号:
23K15417 - 财政年份:2023
- 资助金额:
$ 30.7万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Lung delivery of novel ACE2 variants for COVID-19
针对 COVID-19 的新型 ACE2 变体的肺部输送
- 批准号:
10483042 - 财政年份:2022
- 资助金额:
$ 30.7万 - 项目类别:
ACE2 on gut barrier dysfunction and BRB disruption
ACE2 对肠道屏障功能障碍和 BRB 破坏的影响
- 批准号:
10535485 - 财政年份:2022
- 资助金额:
$ 30.7万 - 项目类别: