Discovery of novel broad-spectrum coronavirus inhibitors

项目2--摘要 该项目的目标是发现新的广谱冠状病毒抑制剂。我们将确定新的广泛的- 使用基于细胞的方法研究病毒复制的冠状病毒光谱抑制剂。我们将通过以下方式实现目标 追求三个目标。(I)筛选和鉴定广谱抑制冠状病毒的新化合物。我们会 使用SARS-CoV-2、MERS-CoV和229E感染试验筛选和鉴定病毒复制的抑制物。 UTMB开发了一种针对SARS-CoV-2的单周期感染系统，可用于HTS活动，网址为 BSL2.在本应用中，我们将该系统扩展到MERS-CoV。我们还将开发一款记者229E 冠状病毒用于抗病毒筛选。(2)开发工具化合物，确定目标蛋白，优化分子。 (3)评估相关的体外和体内模型中的先导化合物，并选择开发IND- 使研究成为可能。提出的基于细胞的方法可能会发现新的抗病毒靶点，而这些靶点可能不是 以目标为基础的抗病毒方法易于处理。

PROJECT 2 – ABSTRACT The goal of this project is to discover novel broad-spectrum coronavirus inhibitors. We will identify new broad- spectrum coronavirus inhibitors of viral replication using a cell-based approach. We will achieve the goal by pursuing three aims. (i) Screen and identify novel compounds for broad-spectrum coronavirus inhibition. We will screen and identify inhibitors of viral replication using SARS-CoV-2, MERS-CoV, and 229E infection assays. UTMB has developed an single-cycle infection system for SARS-CoV-2 that can be used for HTS campaign at BSL2. In this application, we will expand this system to MERS-CoV. We will also develop a reporter 229E coronavirus for antiviral screen. (ii) Develop tool compounds, determine target protein, and optimize molecules. (iii) Evaluate lead compounds in relevant in vitro and in vivo models and select Development Candidate for IND- enabling studies. The proposed cell-based approach may discover novel antiviral targets that may not be tractable for target-based antiviral approach.