Discovery of novel broad-spectrum coronavirus inhibitors

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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.