In silico Study of Some Dexamethasone Analogs and Derivatives against SARs-CoV-2 Target: A Cost-effective Alternative to Remdesivir for Various COVID Phases

Abstract

Aim: The black market for Remdesivir for the treatment of COVID-19 is surging in the world. This condition leads to the uprising of drugs from the common hospital inventory, of which Dexamethasone is an effective weapon to be employed against the coronavirus. Background: Remdesivir is an intravenous nucleotide prodrug of an adenosine analog. Dexamethasone was tested in hospitalized patients with COVID-19 in the UK’s national clinical trial and was found to benefit critically ill patients. Therefore, it could be a better alternative. Objective: A computational approach of molecular docking was performed to determine the binding interactions ability between the selected 3D-models of COVID-19 protease and inflammatory targets with suggested modified ligand compounds through Autodock v.1.5.6 software that also establishes the plausible mechanism. Method: Dexamethasone had a constructive response where we utilized the structural modification technique in which molecules (icomethasone, betnesol, topicort, flumethasone, paramethasone, triamcinolone, and doxi-betasol) bearing the same pharmacophore as in dexamethasone (ring-A as it is responsible for the binding of the compound to the steroidal receptor), were selected from available drug bank to observe the response of these modified structures against SARs-CoV-2. Desmond Simulation Package was used to run MD simulations for 100 ns following the docking calculations to assess the steady nature and conformational stability of the Dexamethasone-17-acetate-SARs- CoV-2 main protease complexes. Result: Dexamethasone-17-acetate, the best analog, demonstrated a better pharmacological response than the parent compound and provided information for further designing active inhibitors against inflammatory targets activated by the coronavirus attack. The maximum RMSD value of the Cα-backbone of the SARs-CoV-2 main protease protein is 3.6Å, indicating that the Dexamethasone- 17-acetate-6LU7 protein complex was retained continuously throughout the simulation time. Conclusion: The present investigation was a search for inhibitors that will help recover patients suffering from COVID and for prophylactic use.