Virology Core

病毒学核心-摘要 UTMB-Novartis预防大流行联盟的病毒学核心目标是支持交付 通过追求三个目标，对拟议的临床候选人进行评估。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)记者病毒的制备 库存量为高吞吐量的库屏幕。(Ii)对命中或线索进行抗病毒频谱分析。目标2.行动模式 以及抗药性研究。病毒学核心将通过以下途径进行作用模式和抗药性研究 三个子目标。(I)目标去卷积。(2)对已知病毒靶标的抑制剂进行抗药性分析。(三)健身 耐药病毒的分析。目的3.抑制剂的体内评价。我们将评估抑制剂的体内疗效 在动物模型中通过三种活动。(I)将根据以下情况开始实施三个治疗时间表 综合治疗：感染前治疗(预防)、感染后立即治疗、感染后 暴露治疗。(Ii)还将进行不同剂量的治疗，以确定剂量反应。 将建立这些抑制剂的药代动力学和药效学。(Iii)综合治疗将是 用于确定要克服的两种不同类型的抑制剂的相加、协同或拮抗作用 抵抗。

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.