Discovery of novel Henipavirus inhibitors

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PROJECT 3 – ABSTRACT The goal of this project is to discover novel henipavirus inhibitors. Henipavirus is a deadly airborne respiratory pathogen that are under-researched and poorly understood. Antiviral therapy is urgently needed for henipaviruses for pandemic preparedness. We will achieve the goal by pursuing three aims. (i) Screen and identify novel compounds for Nipah and/or Hendra virus inhibition. Since Nipah and Hendra viruses should be handled at BSL4, it is challenging to perform high-throughput screen at high containment. To overcome this bottleneck, we will use a BSL2 Cedar henipavirus as a surrogate system for antiviral screen. Hits identified from the Cedar henipavirus assay will be validated in Hendra and Nipah viruses at the BSL4 facility. (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.