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