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.