Virology Core

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

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.