Computer Aided Drug Design Virtual Screening For Novel Inhibitors Of SARS-Cov2 M^pro And CDK2

Computer virtual screening refers to the use of high-performance computers to perform virtual screening of drugs based on computational chemistry theory.Virtual screening can greatly reduce the number of compounds to be screened through experiments,and at the same time can improve the efficiency of discovery of effective compounds.Corona Virus Disease 2019（COVID-19）,referred to as"New Coronary Pneumonia",is a type of acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2（SARS-Co V-2）infection.M^prois one of the main targets for treating COVID-19.The current research on M^promainly focuses on the repurposing of old drugs,and there are only a few novel ligands that inhibit M^pro.In this research,we used computational free energy calculation to screen a compound library against M^pro,and discovered four novel compounds with the two best compounds（AG-690/13507628 and AG-690/13507724）having experimental measured IC₅₀of just under 3μM and low cell toxicity.Detailed decomposition of the interactions between the inhibitors and M^proreveals key interacting residues and interactions that determine the activity.The results from this study should provide a basis for further development of anti-SARS-Co V-2 drugs.Cyclin-dependent protein（CDK）is a serine/threonine protein kinase family with a total of 20members and CDK family cooperating with cyclin becomes an important factor in the regulation of cell cycle.Cyclin-dependent kinase 2 is an important member of the CDK family.In dividing cells,CDK2 is a core cell cycle regulator,which is very active from the late G1 phase to the entire S phase.In this research,we found several compounds with the same chemical framework through virtual screening.And these compounds have good inhibitory activity and potential for modification.