Discovery of novel Henipavirus inhibitors

新型亨尼帕病毒抑制剂的发现

基本信息

批准号：
10845863
负责人：
Thomas William Geisbert
金额：
$ 231.77万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-16 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10845863
关键词：
2019-nCoV African Green Monkey Animals Antiviral Agents Antiviral Therapy Automation Bangladesh Biochemical Biological Assay Biology Case Fatality Rates Cells Chemicals Communicable Diseases Containment Coronavirus Country Dengue Dengue Virus Development Disease Disease Outbreaks Drug Design Drug Targeting Drug resistance Encephalitis Evaluation Exclusion Family Flavivirus Generations Goals Hamsters Hendra Virus Henipavirus Human In Vitro India Infection Lead Luciferases Malaysia Maps Medical Miniaturization Modeling Modernization Mutation Nipah Virus Paramyxovirus Pathogenicity Persons Pharmaceutical Chemistry Phase I/II Clinical Trial Phenotype Philippines Proteins Recombinants Research Rodent Services Structure Structure-Activity Relationship System Technology Testing Texas Therapeutic Triage Universities Vaccines Variant Viral Viral Genes Virus animal efficacy biophysical techniques biosafety level 4 facility clinical candidate combat cytotoxicity drug discovery drug resistant virus efficacy study high throughput screening human pathogen in vivo in vivo Model inhibitor lead optimization man member novel pandemic potential pandemic preparedness pharmacokinetics and pharmacodynamics pre-clinical preclinical development protective efficacy respiratory respiratory pathogen reverse genetics safety study screening small molecule tool transmission process virology whole genome

项目摘要

PROJECT 3 – ABSTRACT The goal of this project is to discover novel henipavirus inhibitors. Henipavirus is a deadly airborne respiratory pathogen that are under-researched and poorly understood. Antiviral therapy is urgently needed for henipaviruses for pandemic preparedness. We will achieve the goal by pursuing three aims. (i) Screen and identify novel compounds for Nipah and/or Hendra virus inhibition. Since Nipah and Hendra viruses should be handled at BSL4, it is challenging to perform high-throughput screen at high containment. To overcome this bottleneck, we will use a BSL2 Cedar henipavirus as a surrogate system for antiviral screen. Hits identified from the Cedar henipavirus assay will be validated in Hendra and Nipah viruses at the BSL4 facility. (ii) Develop tool compounds, determine target protein, and optimize molecules. (iii) Evaluate lead compounds in relevant in vitro and in vivo models and select Development Candidate for IND-enabling studies. The proposed cell-based approach may discover novel antiviral targets that may not be tractable for target-based antiviral approach.

项目 3 – 摘要该项目的目标是发现新型亨尼帕病毒抑制剂，亨尼帕病毒是一种致命的空气传播呼吸道病毒。迫切需要抗病毒治疗。我们将通过实现三个目标来实现这一目标：(i) 筛查和预防流行病。确定抑制尼帕病毒和/或亨德拉病毒的新化合物，因为尼帕病毒和亨德拉病毒应该是有效的。在 BSL4 处理时，要克服这个问题，在高封闭性下进行高通量筛选是一项挑战。瓶颈，我们将使用 BSL2 Cedar henipavirus 作为从抗病毒筛选中鉴定的替代系统。 Cedar henipavirus 检测将在 BSL4 设施的 Hendra 和 Nipah 病毒中进行验证 (ii) 开发工具。 (iii) 评估相关体外先导化合物和体内模型，并选择用于 IND 研究的开发候选者。方法可能会发现新的抗病毒靶点，而基于靶点的抗病毒方法可能无法处理这些靶点。