Assessment of activity of chalcone compounds as inhibitors of 3-chymotrypsin like protease (3CL(Pro)) of SARS-CoV-2: in silico study

The COVID-19 is still pandemic due to emerging of various variant of concern of SARS-CoV2. Hence, it is devastating the world, causing significant economic as well as social chaos. This needs great effort to search and develop effective alternatives along with vaccination. Therefore, to continue drug discovery endeavors, we used chalcone derivatives to find an effective drug candidate against SARS-CoV2. Chalcone is a common simple scaffold that exists in many diets as well as in traditional medicine. Natural as well as synthetic chalcones have shown numerous interesting biological activities and are also effective in fighting various diseases. Hence, various computational methods were applied to find out potential inhibitors of 3CL(Pro) using a library of 3000 compounds of chalcones. Firstly, the screening by structure-based pharmacophore model yielded 84 hits that were subjected to molecular docking. The top 10 docked compounds were characterized for stability by using 100 ns molecular dynamic (MD) simulation approach. Further, the binding free energy calculation by MMPBSA showed that four compounds bind to 3CL(Pro) enzyme with high affinity, i.e., − 87.962 (kJ/mol), − 66.125 (kJ/mol), − 59.589 (kJ/mol), and − 66.728 (kJ/mol), respectively. Since chalcone is a common simple scaffold that is present in many diets as well as in traditional medicine, we suggest that screened compounds may emerge as promising drug candidates for SARS-CoV-2. These compounds may be investigated in vitro to evaluate the efficacy against SARS-CoV-2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11224-022-01887-2.