Design of SARS-CoV-2 Main Protease Inhibitors by Computer Aided Drug Design in Collaboration with the COVID Moonshot Initiative
Advisor(s)
Dr. John Thurmond; Illinois Mathematics and Science Academy
Discipline
Chemistry
Start Date
21-4-2021 8:50 AM
End Date
21-4-2021 9:05 AM
Abstract
In early December 2019, a novel coronavirus pandemic broke out in the city of Wuhan, China Hubei Province. As of the end of February 2021, nearly 114 million people have been infected worldwide, and over 513 thousand have died in the United States alone.. SARS-CoV-2 is a positive-sense, enveloped, single-stranded RNA Betacoronavirus and is the disease-causing agent for Covid-19. Of many SARS-CoV-2’s proteins, its main protease (MPro) is the primary target for drug discovery efforts. The COVID Moonshot project focuses on inhibitors for mPro using the crowdsourced medicinal chemistry insights of companies and chemists around the world. A fragment from the COVID Moonshot database (x2600) was selected as a starting point to design new compounds. Using molecular simulation software such as SeeSAR, new compounds were designed and their binding affinities computed. ADME prediction websites such as AdmetSAR and SwissADME, were utilized to compute the new compounds' pharmacokinetic and physicochemical properties. The newly designed compounds improve on aspects such as binding affinity, torsion angles, ligand lipophilicity efficiency, and pharmacokinetic properties.
Design of SARS-CoV-2 Main Protease Inhibitors by Computer Aided Drug Design in Collaboration with the COVID Moonshot Initiative
In early December 2019, a novel coronavirus pandemic broke out in the city of Wuhan, China Hubei Province. As of the end of February 2021, nearly 114 million people have been infected worldwide, and over 513 thousand have died in the United States alone.. SARS-CoV-2 is a positive-sense, enveloped, single-stranded RNA Betacoronavirus and is the disease-causing agent for Covid-19. Of many SARS-CoV-2’s proteins, its main protease (MPro) is the primary target for drug discovery efforts. The COVID Moonshot project focuses on inhibitors for mPro using the crowdsourced medicinal chemistry insights of companies and chemists around the world. A fragment from the COVID Moonshot database (x2600) was selected as a starting point to design new compounds. Using molecular simulation software such as SeeSAR, new compounds were designed and their binding affinities computed. ADME prediction websites such as AdmetSAR and SwissADME, were utilized to compute the new compounds' pharmacokinetic and physicochemical properties. The newly designed compounds improve on aspects such as binding affinity, torsion angles, ligand lipophilicity efficiency, and pharmacokinetic properties.