Fragment-based drug discovery and synthesis of SARS-CoV-2 therapeutics
Session Number
Project ID: MEDH 34
Advisor(s)
Dr. John Thurmond, Illinois Mathematics and Science Academy
Discipline
Medical and Health Sciences
Start Date
20-4-2022 10:45 AM
End Date
20-4-2022 11:00 AM
Abstract
During the COVID-19 pandemic, the usual drug development timeline has been substantially condensed. This shortened timeline aims to facilitate the discovery of a safe and effective therapy as soon as possible, as the number of global COVID cases rise. Moreover, the COVID Moonshot open-sourced initiative facilitates the accelerated development of a COVID antiviral. After the published fragment screening on the main protease (MPro) of SARS-CoV2 yielded 66 fragment hits, 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 compounds were produced from the chosen fragment to further investigate by looking at ADME properties. After evaluating predicted drug safety, molecules with the best projected effectiveness were selected for synthesis. The synthesized compounds were then evaluated with nuclear magnetic resonance (NMR) and compared against starting compounds and predicted data to ensure that the proper compound was produced. Thin-layer chromatography (TLC) was also used to verify purity of the compounds. Confirmed compounds will likely proceed to collaboration with the COVID Moonshot consortium.
Fragment-based drug discovery and synthesis of SARS-CoV-2 therapeutics
During the COVID-19 pandemic, the usual drug development timeline has been substantially condensed. This shortened timeline aims to facilitate the discovery of a safe and effective therapy as soon as possible, as the number of global COVID cases rise. Moreover, the COVID Moonshot open-sourced initiative facilitates the accelerated development of a COVID antiviral. After the published fragment screening on the main protease (MPro) of SARS-CoV2 yielded 66 fragment hits, 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 compounds were produced from the chosen fragment to further investigate by looking at ADME properties. After evaluating predicted drug safety, molecules with the best projected effectiveness were selected for synthesis. The synthesized compounds were then evaluated with nuclear magnetic resonance (NMR) and compared against starting compounds and predicted data to ensure that the proper compound was produced. Thin-layer chromatography (TLC) was also used to verify purity of the compounds. Confirmed compounds will likely proceed to collaboration with the COVID Moonshot consortium.