This proposal aims to identify the SARS-CoV-2 pseudoknot binding agent that inhibits -1 programmed ribosomal frameshifting. The objective is divided into four groups: virtual screening of the library database on the PDB ID 7LYJ structure of SARS-CoV-2 pseudoknot, biological screening of the RNA library against dual-luciferase reporter system assay, antiviral activity of HITS from dual luciferase frameshift assay, validation of RNA binding using surface plasma resonance studies, and cytotoxicity and in-vitro ADME profiling of active compounds.
The project focuses on developing a robust virtual screening model to identify RNA binding compounds having affinity for SARS-CoV-2 pseudoknot, determining if inhibitors have the potential to inhibit the expression of pseudoknot control firefly luciferase, and understanding how the discovery of effective pseudoknot-targeting ligands impact the development of antiviral therapies against SARS-CoV-2.