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Virology Core

病毒学核心

基本信息

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
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/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

项目摘要

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通过追求三个目标，提出临床候选人。目标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。(i)报告病毒的制备用于高通量文库筛选的储备物。(ii)命中或线索的抗病毒谱分析。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。(iii)健身抗性病毒分析。目标3。抑制剂的体内评价。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)将根据以下时间点的开始进行三次治疗时间表：复合治疗：感染前治疗（预防性）、感染后立即治疗和感染后治疗。暴露治疗(ii)还将进行不同剂量的治疗以确定剂量反应。将确定抑制剂的药代动力学和药效学。(iii)联合治疗将是进行测定两种不同类型抑制剂的相加、协同或拮抗作用，以克服阻力