Molecular Simulation of the Effect of Electron Donor/Acceptor Groups on Fluvoxamine/Serotonin Interactions as a Strategy for COVID‐19 Mitigation

Abstract

Fluvoxamine has been proven in studies to improve the immune system by reabsorbing serotonin and to be beneficial in limiting the spread of covid‐19 (in the early stages of the disease). The interaction between pristine fluvoxamine drug and serotonin, as well as the interaction between NO2/NH2 doped fluvoxamine drug and serotonin, was investigated in this work using the quantum theory of atom in the molecule (QTAIM) and density‐functional theory (DFT) at the B3LYP/6‐311+G (d,p) (gas phase and water media) computational level. The NH2 and NO2 doping on fluvoxamine significantly increased the adsorption energy of serotonin and improved the dipole moment, solvent energy, chemical hardness/softness, and charge/energy transfer. On the other hand, according to the results of this study, NH2 doping compared to NO2 had no significant effect on the electronic properties such as HOMO/LUMO orbital energy and its gap. From the results, the binding energy of the most stable structure (Complex‐A) was measured to be 12.59 and 11.65 kcal/mol. Based on the electronic structure analysis, an assessment of the stability of the studied systems in the gas phase reveals the following trend: Fluvoxamine‐NH2>Fluvoxamine‐NO2>Fluvoxamine‐NH2/Ser>Fluvoxamine‐NO2/Ser, with corresponding energy gaps of 4.12, 2.65, 1.98, and 1.63 eV, respectively. Therefore, NH2 doping on fluvoxamine is a harmless electronic interaction and does not significantly change the properties of the drug. It seems that increasing the absorption energy by doping the NH2 functional group can help reduce the therapeutic dose and make fluvoxamine more effective.