Presented at the Japan Super Science Fair (JSSF) 2021
John Thurmond, PhD; Illinois Mathematics and Science Academy
Chemicals and Drugs | Chemistry | Medicine and Health Sciences
During the COVID-19 pandemic, the usual drug development timeline has been substantially condensed. This shortened timeline aims to allow for a safe and effective therapy to be discovered as soon as possible as the number of global COVID cases rise. Moreover, the COVID Moonshot open-sourced initiative has allowed the development of a COVID antiviral to accelerate. After the published fragment screening on the main protease (MPro) of SARS-CoV2 yielded 66 fragment hits, a fragment (x0434) was selected to build novel compounds. SeeSAR was used to gather preliminary knowledge of the three-dimensional structure of the biomolecular targeted protein and selected fragment interaction. SeeSAR analysis features allowed for the visualization of the ligand-protein structure and identification of key interactions driving binding affinity. Nearly four hundred possible compounds were produced from the chosen fragment to investigate ADME properties further. The compiled data was evaluated to look for no Lipinski rule violations, high GI absorption levels, no PAINS violations, and few CYP inhibitors. The most promising compounds designed from the above criteria will move forward for synthesis. Additionally, these compounds will likely proceed to collaboration with the COVID Moonshot consortium towards possible preparation and distribution for assays against the MPro.
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Fragment-Based Drug Discovery of SARS-CoV-2 Therapeutics.
Retrieved from: https://digitalcommons.imsa.edu/student_pr/86