Ferrocenyl Hydroxy Methyl Coupled Caffeine Synthesis, Density Functional Theory, ADME Prediction and Docking Analysis of It's Binding Interactions to Coronavirus Main Protease

The COVID-19 pandemic has made the world aware of how crucial the development of cost-effective and scalable antiviral drugs is. Here we report the synthesis of caffeine-based 8-[(ferrocenyl)(hydroxy)methyl]-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (FHC), and its use as an inhibitor of protease (Mpro), an essential enzyme for SARS-CoV-2 viral replication. FHC was modelled through density functional theory to get an insight of its properties, and fully characterized through conventional techniques. Its activity against Mpro was investigated using a molecular docking approach, showing excellent binding affinity to the catalytic dyad of His41 and Cys145 and the active sites of Mpro with energies score ranging from -6.7 to -7.0 kcal/mol. The affinity of conformers to bind to the active pocket was 44%. Based on a detailed investigation, it appears that FHC has a safe ADME profile, and that it could be a potential inhibitor for Mpro of SARS-CoV-2.