Virology Core

病毒学核心

• 批准号: 10514148
• 负责人: Xuping Xie
• 金额: $ 1087.8万
• 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/10514148
• 关键词: 2019-nCoV; Academia; Affect; Aftercare; Alphavirus; Animal Model; Antiviral Agents; Binding; Biochemical; Biological Assay; Biological Process; Biology; Cells; Centers for Disease Control and Prevention (U.S.); Clinic; Clinical; Collaborations; Combined Modality Therapy; Computer Assisted; Containment; Coronavirus; Dengue; Development; Disease; Dose; Drug Screening; Drug resistance; Evaluation; Filovirus; Flavivirus; Funding; Funding Opportunities; Goals; HIV/HCV; Henipavirus; Histopathology; In Vitro; Industry; Infection; Institution; Joint Ventures; Laboratories; Libraries; Machine Learning; Measures; Medical; Modeling; Mutation; Nipah Virus; Nucleosides; Organ; Paramyxovirus; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Preparation; Protease Inhibitor; Proteins; Pyrimidine; RNA Polymerase Inhibitor; RNA-Directed RNA Polymerase; Recombinants; Reporter; Research; Resistance; Safety; Spectrum Analysis; Testing; Texas; Therapeutic; TimeLine; Translational Research; United States National Institutes of Health; Universities; Viral; Viral Load result; Viral Proteins; Virus; Virus Replication; Work; base; clinical candidate; cohesion; drug development; drug discovery; drug resource; fitness; high throughput screening; in vitro activity; in vivo; in vivo evaluation; inhibitor; inquiry-based learning; interest; lead optimization; member; nucleotide analog; pandemic disease; pandemic preparedness; pathogen; pharmacokinetics and pharmacodynamics; pre-clinical; preclinical development; prophylactic; rational design; recombinant virus; resistance mutation; response; screening; synergism; virology; virus culture

VIROLOGY CORE - ABSTRACT The goal of the Virology Core at UTMB-Novartis Alliance for Pandemic Preparedness is to support the delivery of the proposed clinical candidates by pursuing three aims. Aim 1. In vitro evaluation of inhibitors. The Virology Core will evaluate in vitro activities of compounds by pursuing two sub-aims. (i) Preparation of reporter virus stocks for high-throughput library screen. (ii) Antiviral spectrum analysis of hits or leads. Aim 2. Mode-of-action and drug resistance studies. The Virology Core will pursue mode-of-action and drug resistance studies through three sub-aims. (i) Target deconvolution. (ii) Resistance analysis of inhibitors of known viral targets. (iii) Fitness analysis of resistant virus. Aim 3. In vivo evaluation of inhibitors. We will evaluate the in vivo efficacy of inhibitors in animal models through three activities. (i) Three treatment timelines will be performed based on the start of compound treatment: pre-infection treatment (prophylactic), immediate treatment after infection, and post- exposure treatment. (ii) Treatment with different doses will also be performed to establish dose responses. Pharmacokinetics and pharmacodynamics will be established for the inhibitors. (iii) Combination therapy will be performed to determine additive, synergistic, or antagonistic effect of two different types of inhibitors to overcome resistance.

病毒学核心 - 摘要 UTMB-Novartis联盟的病毒学核心的目标是支持交付 在拟议的临床候选人中追求三个目标。目标1。抑制剂的体外评估。病毒学 核心将通过追求两个亚aim来评估化合物的体外活性。 （i）准备记者病毒 高通量图书馆屏幕的库存。 （ii）击球或铅的抗病毒光谱分析。目标2。行动方式 和耐药性研究。病毒核心将通过 三个子。 （i）目标反卷积。 （ii）对已知病毒靶标的抑制剂的抗性分析。 （iii）健身 抗性病毒的分析。目标3。抑制剂的体内评估。我们将评估抑制剂的体内功效 在动物模型中通过三个活动。 （i）将根据开始的三个治疗时间表 化合物治疗：感染前治疗（预防性），感染后立即治疗和 暴露疗法。 （ii）还将使用不同剂量的治疗来建立剂量反应。 将为抑制剂建立药代动力学和药效学。 （iii）组合疗法将是 执行以确定两种不同类型抑制剂的添加剂，协同或拮抗作用 反抗。