Pandemic Assistance Core

项目摘要/摘要 大流行援助核心将使AViDD中心的调查人员能够快速开发抗病毒药物 SARS-CoV-2和其他具有大流行潜力的RNA病毒的治疗。这一核心将为 对所有七个项目开发的化合物进行严格的体外和体内测试，特别是 强调提供无与伦比的BSL3和ABSL3容量。我们将快速有效地完善我们的目标 并从我们项目过程中的一系列通过/不通过决策中进行向下选择，提供漏斗 结构，以便在体外和体内快速确定最有希望的候选者。化合物将在 无论是预防模式还是治疗模式。随着我们的项目采取独特的方法来瞄准病毒的生命周期， 每个项目的主要候选人也将接受联合测试，以确定协同效应。最有希望的 随后，将派往翻译加速器核心部门进一步发展。至 为了完成这项工作，我们召集了一支杰出的跨学科调查团队， 在病毒学、药物开发和用于药物筛选的啮齿动物模型方面有丰富的经验。我们还带来了 使用人体气液界面(ALI)测试生理系统中化合物的高度创新方法 模型和人类成年肺器官(ALO)。我们的目标是提供行业级的筛选和 挑选最有前途的候选药物。

PROJECT SUMMARY/ABSTRACT The Pandemic Assistance Core will enable investigators in this AViDD center to rapidly develop antiviral therapeutics for SARS-CoV-2 and other RNA viruses of pandemic potential. This core will provide capacity for rigorous in vitro and in vivo testing of compounds developed across all seven Projects, with a particular emphasis on providing unparalleled BSL3 and ABSL3 capacity. We will quickly and efficiently refine our targets and down-select from a series of go/no-go decisions over the course of our project, providing a funnelling structure to rapidly identify the most promising candidates both in vitro and in vivo. Compounds will be tested in both prophylactic and therapeutic models. As our Projects take unique approaches to target the viral life cycle, lead candidates from each project will also be tested in combination to identify synergism. The most promising of the lead candidates will then be sent for further development within the Translation Accelerator Core. To achieve this work we have brought together an outstanding and interdisciplinary team of investigators with significant experience in virology, drug development, and rodent models for drug screening. We also bring highly innovative approaches to test compounds in physiologic systems using human air-liquid interface (ALI) models and human adult lung organoids (ALO). We aim to provide industry-level capacity for screening and selecting the most promising drug candidates.