Title:In silico Study of Some Dexamethasone Analogs and Derivatives against
SARs-CoV-2 Target: A Cost-effective Alternative to Remdesivir for Various
COVID Phases
Volume: 2
Issue: 4
Author(s): Ruchi Pandey, Itishree Dubey, Iqrar Ahmad, Debarshi Kar Mahapatra, Harun Patel and Pranesh Kumar*
Affiliation:
- Department of Pharmacology, Aryakul College of Pharmacy and Research, Gauri-
Bijnaur Road, Natkur, Adjacent to CRPF Base Camp, Lucknow 226002, Uttar Pradesh, India
Keywords:
COVID-19, SARs-CoV-2, molecular docking, dexamethasone, dexamethasone-17-acetate, Remdesivir.
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.
Methods: 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.
Results: 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.
