Fusion Inhibitors of H5N1

H5N1 融合抑制剂

基本信息

  • 批准号:
    8375867
  • 负责人:
  • 金额:
    $ 32.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-03-01 至 2014-02-28
  • 项目状态:
    已结题

项目摘要

Emerging avian influenza viruses pose an increasing threat to domestic poultry and human health. The influenza virus hemagglutinin (HA) is an attractive drug target because they are essential for viral entry, and indispensable for virus replication. We hypothesize that fusion inhibitors currently under development in this program will be potent against diverse virus strains, especially HPAI viruses. Specific aims to further develop these inhibitors are:Aim 1. Identify fusion inhibitors that are potent against diverse strains of H5N1 influenza viruses. Our preliminary studies have identified a group of lead compounds that have EC50 values in single digit nanomoles across diverse influenza virus strains including H5N3 (vaccine strain), H3N2, H1N1 and type B. To identify potential candidates for preclinical and eventual clinical studies against HPAI H5N1 viruses, we propose to develop a library of analogs based on the initial lead. We propose to measure the inhibitory potencies of candidate compounds against diverse strains of H5N1 influenza viruses. Lead compounds identified from these studies will be advanced to preclinical studies as a component of Program 10. Aim 2. Determine the mechanisms of action of HA protein inhibitors.Our preliminary data indicate that the fusion nhibitors we have developed alter the structure of HA. For compounds identified in Aim 1 that are potent against H5N1 viruses, we will determine which step of virus entry is blocked using biological and biochemical assays. To map the binding sites of compounds, we will co-crystallize the HA protein with bound inhibitor, and we will also generate and characterize resistant variants. Recombinant HA will be treated with different proteases in order to map the conformationally sensitive regions. Aim 3. Determine if drug combinations that nclude HA inhibitors provide advantages over existing single-agent therapies in protecting against disease and avoiding drug resistance. A widespread use of HA inhibitors could result in the emergence of drugesistant viruses, similar to the acquisition of drug resistance that has been observed for neuraminidase (NA) and M2 inhibitors. We hypothesize that the use of HA inhibitors in combination with existing NA and/or M2 nhibitors will help counteract drug resistance and decrease the severity of infectious disease.
新出现的禽流感病毒对家禽和人类健康构成越来越大的威胁。的

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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MING LUO其他文献

MING LUO的其他文献

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{{ truncateString('MING LUO', 18)}}的其他基金

Project 1: Small Molecule Entry Inhibitors of Pandemic Viruses
项目1:大流行病毒的小分子进入抑制剂
  • 批准号:
    10522810
  • 财政年份:
    2022
  • 资助金额:
    $ 32.98万
  • 项目类别:
Study of arenavirus assembly
沙粒病毒组装研究
  • 批准号:
    10514372
  • 财政年份:
    2022
  • 资助金额:
    $ 32.98万
  • 项目类别:
Study of arenavirus assembly
沙粒病毒组装研究
  • 批准号:
    10668498
  • 财政年份:
    2022
  • 资助金额:
    $ 32.98万
  • 项目类别:
Fusion Inhibitors of H5N1
H5N1 融合抑制剂
  • 批准号:
    8234181
  • 财政年份:
    2011
  • 资助金额:
    $ 32.98万
  • 项目类别:
STRUCTURE DETERMINATION OF VIRAL NUCLEOPROTEIN COMPLEXES
病毒核蛋白复合物的结构测定
  • 批准号:
    8362196
  • 财政年份:
    2011
  • 资助金额:
    $ 32.98万
  • 项目类别:
STRUCTURE DETERMINATION OF VIRAL NUCLEOPROTEIN COMPLEXES
病毒核蛋白复合物的结构测定
  • 批准号:
    8170157
  • 财政年份:
    2010
  • 资助金额:
    $ 32.98万
  • 项目类别:
Assembly of the Negative Stranded RNA Virus Core
负链RNA病毒核心的组装
  • 批准号:
    7880321
  • 财政年份:
    2009
  • 资助金额:
    $ 32.98万
  • 项目类别:
Fusion Inhibitors of Influenza Virus
流感病毒融合抑制剂
  • 批准号:
    8309399
  • 财政年份:
    2009
  • 资助金额:
    $ 32.98万
  • 项目类别:
Fusion Inhibitors of Influenza Virus
流感病毒融合抑制剂
  • 批准号:
    7564248
  • 财政年份:
    2009
  • 资助金额:
    $ 32.98万
  • 项目类别:
Fusion Inhibitors of Influenza Virus
流感病毒融合抑制剂
  • 批准号:
    8114134
  • 财政年份:
    2009
  • 资助金额:
    $ 32.98万
  • 项目类别:

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