Fragment-Based Design of SARS-CoV-2 Mpro inhibitors

Abstract SARS-CoV-2 virus has been identified as a causative agent has been identified for COVID19 pandemic. Till date, about more than 6.1 million deaths have been reported due to COVID-19 across the globe. Looking into the current outbreak, there is an urgent need to identify the potential treatment for the disease. The prominence of main protease in the life cycle of virus shapes the main protease as a viable target for design and development of antiviral agents to combat COVID-19. The current study presents the fragment linking strategy to design the novel Mpro inhibitors for COVID-19. Total 2,93,451 fragments from diversified libraries have been screened for their binding affinity towards Mpro enzyme. The best 1600 fragment hits were subjected to fragment joining to achieve 100 new molecules using Schrödinger software. The resulting molecules were further screened for their Mpro binding affinity, ADMET and drug-likeness features. Best 13 molecules were selected and best compound was investigated for its ligand-receptor complex stability through molecular dynamics study using GROMACS software. The resulting molecules have the potential to be further evaluated for COVID-19 drug discovery.