Discovery of novel Henipavirus inhibitors

新型亨尼帕病毒抑制剂的发现

• 批准号: 10514154
• 负责人: Thomas William Geisbert
• 金额: $ 529.18万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 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/10514154
• 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; Crystallization; Dengue; Dengue Virus; Development; Disease; Disease Outbreaks; Drug Design; Drug Targeting; Drug resistance; Encephalitis; Evaluation; 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; base; 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 disease; 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

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的亨尼帕病毒抑制剂。亨尼帕病毒是一种致命的空气传播呼吸道病毒 这些病原体研究不足，了解不多。抗病毒治疗是迫切需要的， 预防流行病的方法。我们将通过追求三个目标来实现这一目标。(i)屏幕和 鉴定用于尼帕病毒和/或亨德拉病毒抑制的新化合物。由于尼帕病毒和亨德拉病毒应该是 由于在BSL 4处理，因此在高包容性下进行高通量筛选具有挑战性。为了克服这个 为了克服这一瓶颈，我们将使用BSL 2雪松亨尼帕病毒作为抗病毒筛选的替代系统。识别的命中来自 将在BSL 4设施中对Cedar henipavirus检测试剂盒进行Hendra和Nipah病毒的验证。(ii)开发工具 化合物，确定目标蛋白，并优化分子。(iii)评价相关体外先导化合物 和体内模型，并选择IND使能研究的开发候选药物。所提出的基于细胞的 这种方法可以发现新的抗病毒靶点，这些靶点对于基于靶点的抗病毒方法来说可能是不容易处理的。