Fusion inhibitors that block host-to-host transmission of SARS-CoV-2
阻止 SARS-CoV-2 宿主间传播的融合抑制剂
基本信息
- 批准号:10237600
- 负责人:
- 金额:$ 75.02万
- 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:2021-08-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:2019-nCoVAddressAffinityAnimalsAntiviral AgentsBindingBiodistributionBiological AssayCOVID-19COVID-19 pandemicCOVID-19 treatmentCell Culture TechniquesCell fusionCell membraneCell surfaceCellsChiropteraCommon ColdCommunitiesCoronavirusCoronavirus InfectionsCouplesDataDevelopmentDiseaseDisease OutbreaksDistalDominant-Negative MutationDoseEndosomesFerretsGlycoproteinsHomes for the AgedHospitalsHumanImmunologicsIn VitroIndividualInfectionInfection preventionIntegration Host FactorsLeadLifeLipidsMediatingMembraneMembrane FusionMiddle East Respiratory Syndrome CoronavirusModelingMolecularMolecular ConformationNamesNosePeptide HydrolasesPeptidesPlayPopulationProcessProphylactic treatmentProteinsRoleSARS coronavirusSevere Acute Respiratory SyndromeSeverity of illnessSurfaceTestingTherapeutic InterventionToxic effectVaccinatedVaccinesViralVirusVirus DiseasesWorld Health OrganizationZoonosesbasebetacoronaviruscell typecytotoxicitydesigndimerexperimental studyfundamental researchgenetic informationimprovedin vivoinhibitor/antagonistmonomernovelnovel coronaviruspandemic diseasepre-clinicalpreclinical studypressurepreventreceptorreceptor bindingresearch clinical testingtransmission processuptakeviral transmissionvirus genetics
项目摘要
Coronaviruses (CoVs) can cause life-threatening diseases. The recently emerging coronavirus-related illness
was named coronavirus disease 2019 (abbreviated “COVID-19”) by the World Health Organization. COVID-19
is caused by SARS-CoV-2. Like its predecessors SARS-CoV and MERS-CoV, SARS-CoV-2 (S-CoV-2) is a
betacoronavirus that is thought to have originated in bats. Originally its spread was animal-to-human, but
human-to-human transmission is now widespread. No vaccines and treatments for COVID-19 are available,
and these are urgently needed to address the outbreak as well as inevitable ongoing infection. Antivirals that
target viral entry into the host cell have been proven effective against a wide range of viruses. In this proposal,
we will apply the results of our fundamental research to the development of novel peptide inhibitors of SARS-
CoV-2 entry. We have designed lipid-conjugated fusion-inhibitory peptides that efficiently inhibit coronavirus
infection in in vitro, ex vivo, and in vivo. We propose to synthesize and evaluate novel lipidated peptides that
have enhanced efficacy. These inhibitors will be evaluated for antiviral activity against live SARS-CoV-2 virus.
Promising candidates will be tested in transmission experiments in a ferret model. This application will
determine whether our approach to entry inhibition of SARS-CoV-2 prevents infection in vivo.
1. To optimize antiviral potency of HRC-lipopeptide fusion inhibitors.
2. To pre-clinically evaluate HRC-lipopeptide fusion inhibitors biodistribution, toxicity and protection
against SARS-CoV-2 infection or transmission in vivo.
冠状病毒(CoV)可导致危及生命的疾病。最近出现的冠状病毒相关疾病
被世界卫生组织命名为2019冠状病毒病(简称“COVID-19”)。COVID-19
是由SARS-CoV-2引起的与其前身SARS-CoV和MERS-CoV一样,SARS-CoV-2(S-CoV-2)是一种
被认为起源于蝙蝠的β冠状病毒。最初它是通过动物传播给人类的,
人际传播现已普遍。没有针对COVID-19的疫苗和治疗方法,
这些都是迫切需要的,以解决疫情以及不可避免的持续感染。抗病毒药物,
靶病毒进入宿主细胞已被证明对多种病毒有效。在这项提案中,
我们将把我们的基础研究成果应用于开发新的SARS肽抑制剂-
冠状病毒2型进入。我们设计了脂质结合的融合抑制肽,有效抑制冠状病毒
体外、离体和体内感染。我们建议合成和评估新的脂化肽,
具有增强的功效。将评估这些抑制剂对SARS-CoV-2活病毒的抗病毒活性。
有希望的候选人将在雪貂模型的传播实验中进行测试。此应用程序将
确定我们抑制SARS-CoV-2进入的方法是否能预防体内感染。
1.优化HRC-脂肽融合抑制剂的抗病毒效力。
2.临床前评价HRC-脂肽融合抑制剂的生物分布、毒性和保护作用
抗SARS-CoV-2感染或体内传播。
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)
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Matteo Porotto其他文献
Matteo Porotto的其他文献
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{{ truncateString('Matteo Porotto', 18)}}的其他基金
Design of fusion inhibitors to block measles host-to-host infection
设计融合抑制剂来阻止麻疹宿主间感染
- 批准号:
10753711 - 财政年份:2023
- 资助金额:
$ 75.02万 - 项目类别:
Design of fusion inhibitors to block measles host-to-host infection
设计融合抑制剂来阻止麻疹宿主间感染
- 批准号:
10457081 - 财政年份:2021
- 资助金额:
$ 75.02万 - 项目类别:
Fusion inhibitors that block host-to-host transmission of SARS-CoV-2
阻止 SARS-CoV-2 宿主间传播的融合抑制剂
- 批准号:
10457959 - 财政年份:2021
- 资助金额:
$ 75.02万 - 项目类别:
Fusion inhibitors that block host-to-host transmission of SARS-CoV-2
阻止 SARS-CoV-2 宿主间传播的融合抑制剂
- 批准号:
10668973 - 财政年份:2021
- 资助金额:
$ 75.02万 - 项目类别:
Small molecules to block measles spreading in the central nervous system
小分子阻止麻疹在中枢神经系统中传播
- 批准号:
9986209 - 财政年份:2019
- 资助金额:
$ 75.02万 - 项目类别:
Development of therapeutic fusion inhibitor peptides for Measles encephalitis
开发治疗麻疹脑炎的融合抑制肽
- 批准号:
10414909 - 财政年份:2018
- 资助金额:
$ 75.02万 - 项目类别:
Development of therapeutic fusion inhibitor peptides for Measles encephalitis
开发治疗麻疹脑炎的融合抑制肽
- 批准号:
10178126 - 财政年份:2018
- 资助金额:
$ 75.02万 - 项目类别:
Development of therapeutic fusion inhibitor peptides for Measles encephalitis
开发治疗麻疹脑炎的融合抑制肽
- 批准号:
9973101 - 财政年份:2018
- 资助金额:
$ 75.02万 - 项目类别:
Self-assembling nanoparticles for intranasal delivery of influenza fusion inhibitors
用于鼻内递送流感融合抑制剂的自组装纳米颗粒
- 批准号:
9441694 - 财政年份:2016
- 资助金额:
$ 75.02万 - 项目类别:
Development of novel endosome-targeted Ebola virus entry inhibitors as antiviral agents
开发新型内体靶向埃博拉病毒进入抑制剂作为抗病毒药物
- 批准号:
9431045 - 财政年份:2016
- 资助金额:
$ 75.02万 - 项目类别:
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