Fragment-based inhibitor design for SARS-CoV2 main protease.

ABSTRACT

COVID-19 disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) has resulted in tremendous loss of lives across the world and is continuing to do so. Extensive work is under progress to develop inhibitors which can prevent the disease by arresting the virus in its life cycle. One such way is by targeting the main protease of the virus which is crucial for the cleavage and conversion of polyproteins into functional units of polypeptides. In this endeavor, our effort was to identify hit molecule inhibitors for SARS-CoV2 main protease using fragment-based drug discovery (FBDD), based on the available crystal structure of chromene-based inhibitor (PDB_ID 6M2N). The designed molecules were validated by molecular docking and molecular dynamics simulations. The stability of the complexes was further assessed by calculating their binding free energies, normal mode analysis, mechanical stiffness, and principal component analysis. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-01995-z.