Several coumarin derivatives and their Pd(ii) complexes as potential inhibitors of the main protease of SARS-CoV-2, an in silico approach

The global pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused many fatalities among people and significantly influenced the global economy. Since efficient treatment is not available, the computational methods in biology and chemistry are a promising starting point towards adequate medication. Three previously synthesized coumarin derivatives and their Pd(ii) complexes were examined for the binding affinity towards the M(pro) protein of SARS-CoV-2 by molecular docking and compared to two Food and Drug Administration (FDA) drugs, cinanserin and chloroquine. All of the investigated compounds bind to the active position of the mentioned protein. Coumarin–Pd(ii) complexes showed higher binding affinities compared to the approved drugs. The bindings of the bis(3-(1-((3-chlorophenyl)amino)ethylidene)-chroman-2,4-dione) palladium(ii) complex, its corresponding ligand, and cinanserin to SARS-CoV-2 M(pro) were further subjected to the molecular dynamics simulations. The binding free energies, computed by MM/PBSA approach were analyzed in detail and the importance of specific interactions outlined. These results showed that the molecules bearing structural similarity to the approved drugs and their complexes have the potential to inhibit the functional activity of SARS-CoV-2 protease and further experimental studies should be undertaken.