Systematic In Silico Studies of Corticosteroids and Its Binding Affinities with Glucocorticoid Receptor for Covid-19 Treatment: Ab-Initio, Molecular Docking and MD Simulation Studies

Corticosteroids are a form of medication that helps to reduce inflammation in the body. They also suppress the body immune system and are prescribed as medicines to treat diseases such as asthma, arthritis, lupus, and allergies because they reduce swelling, itching, redness, and allergic reactions. Further, corticosteroids have been recommended for use in different formulations and doses with varying durations in patients suffering with Covid-19 infection. In view of these facts, most commonly used corticosteroids namely, dexamethasone, prednisolone and hydrocortisone have been chosen in this study. Molecular geometries of these steroids have been optimized using density functional theory technique at B3LYP/6-31 + G(d,p) level. Further, optimized structures have been used for molecular docking that has been performed on SwissDock web server. The binding energies between corticosteroids and residues of the glucocorticoid receptor (1M2Z) represent that there exist several binding sites between drug molecules and residues of the target protein. Therefore, most preferred binding sites are taken for the molecular dynamics simulation which elucidates the stability of drug-protein complexes. Results have been used to discuss the binding affinities of dexamethasone, prednisolone and hydrocortisone with protein receptor along with various electronic properties of the corticosteroid drugs.