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

基本信息

  • 批准号:
    10457081
  • 负责人:
  • 金额:
    $ 56.12万
  • 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:
    2021-08-09 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Measles (MeV) causes disease worldwide despite efforts towards eradication by vaccine, largely because it is spread so readily between people. Acute MeV infection causes immune amnesia, resulting in increased susceptibility to other infectious diseases. In addition, rare but severe neurological complications can develop several years after measles due to persistent MeV infection of the central nervous system. People with impaired cellular immunity are at increased risk of developing severe measles, but often cannot be vaccinated since the vaccine virus itself can lead to fatal illness. There is no specific therapy for acute or persistent MeV manifestations. A successful vaccination campaign could have eradicated MeV more than 20 years ago. As today, mainly due to social issue (e.g., antivaxxer movement), eradication is not in sight. The recent resurgence of measles in the U.S. highlights the need of effective measure to prevent host-to-host transmission at the moment of the outbreak surge. We have applied the results of fundamental research to develop a new antiviral strategy for MeV, based on inhibiting membrane fusion during MeV entry. This application will test whether our antiviral approach prevents inter-host transmission and therefore fill this medical demand. Our strategy is based MeV fusion inhibitors (i.e., lipid conjugated peptides) that self-assemble in stable nanoparticles until they reach the target cells were, they integrated into the cell membrane. We have recently shown that this strategy works effectively for SARS-CoV-2. We propose to chemical engineer these inhibitors to optimize 1) the antiviral potency, 2) the conditions under which the peptides self-assemble, 3) the insertion on the target cell membrane, and 5) in vivo biodistribution. Our work will be tested in vitro, ex vivo, and in vivo using a natural model of morbillivirus infection (Canine Distemper Virus -CDV- in Ferrets). 1. To use protein engineering to optimize the self-assembling properties and antiviral potency of HRC-peptide fusion inhibitors. 2. To evaluate the protection afforded by HRC peptide fusion inhibitors against CDV infection in vivo and provide proof of concept for pre-clinical development.
麻疹(MeV)在世界范围内引起疾病,尽管努力根除

项目成果

期刊论文数量(0)
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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:
    $ 56.12万
  • 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:
    $ 56.12万
  • 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:
    $ 56.12万
  • 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:
    10237600
  • 财政年份:
    2021
  • 资助金额:
    $ 56.12万
  • 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:
    $ 56.12万
  • 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:
    $ 56.12万
  • 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:
    $ 56.12万
  • 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:
    $ 56.12万
  • 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:
    $ 56.12万
  • 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:
    $ 56.12万
  • 项目类别:

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