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-诺华大流行病防范联盟病毒学核心的目标是支持交付 通过追求三个目标来确定拟议的临床候选人。目的 1. 抑制剂的体外评价。病毒学 Core 将通过追求两个子目标来评估化合物的体外活性。 (一)报告病毒的制备 用于高通量库筛选的库存。 (ii) 命中或先导化合物的抗病毒谱分析。目标 2. 作用方式 和耐药性研究。病毒学核心将通过以下方式进行作用模式和耐药性研究 三个子目标。 (i) 目标反卷积。 (ii) 已知病毒靶点抑制剂的耐药性分析。 (三) 健康状况 耐药病毒分析。目标 3. 抑制剂的体内评估。我们将评估抑制剂的体内功效 通过三项活动在动物模型中。 (i) 根据开始时间将执行三个治疗时间表 复合治疗：感染前治疗（预防性）、感染后立即治疗、感染后治疗 暴露治疗。 (ii) 还将进行不同剂量的治疗以确定剂量反应。 将建立抑制剂的药代动力学和药效学。 (iii) 联合治疗 进行以确定两种不同类型的抑制剂的相加、协同或拮抗作用以克服 反抗。