Event Title

Fragment-Based Drug Discovery of SARS-CoV-2 Therapeutics

Advisor(s)

Dr. John Thurmond; Illinois Mathematics and Science Academy

Discipline

Medical and Health Sciences

Start Date

21-4-2021 10:45 AM

End Date

21-4-2021 11:05 AM

Abstract

The usual drug development timeline has been substantially condensed as the number of global COVID cases rise in order to allow for a safe and effective therapy to be discovered as soon as possible. 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 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 compound interaction. SeeSAR analysis features allowed for the visualization of the ligand-protein structure and identification of key interactions driving binding affinity. Over three hundred possible compounds were produced from the chosen fragment to investigate ADME properties further. The compiled data showed great promise with no Lipinski rule violations, high GI absorption levels for all compounds, no PAINS violations, and very few CYP inhibitors. The most promising compounds designed from the above data and overall research were submitted for further analysis through our collaboration with the COVID Moonshot consortium towards possible preparation and distribution for assays against the MPro.

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Apr 21st, 10:45 AM Apr 21st, 11:05 AM

Fragment-Based Drug Discovery of SARS-CoV-2 Therapeutics

The usual drug development timeline has been substantially condensed as the number of global COVID cases rise in order to allow for a safe and effective therapy to be discovered as soon as possible. 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 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 compound interaction. SeeSAR analysis features allowed for the visualization of the ligand-protein structure and identification of key interactions driving binding affinity. Over three hundred possible compounds were produced from the chosen fragment to investigate ADME properties further. The compiled data showed great promise with no Lipinski rule violations, high GI absorption levels for all compounds, no PAINS violations, and very few CYP inhibitors. The most promising compounds designed from the above data and overall research were submitted for further analysis through our collaboration with the COVID Moonshot consortium towards possible preparation and distribution for assays against the MPro.