Inhibitory activity of hydroxychloroquine on COVID-19 main protease: An insight from MD-simulation studies

Highlights

• Molecular Docking studies reveals that hydroxychloroquine (HCQ) possesses a high docking score and interaction energy compared to other small drug molecule with the COVID-19 main protease.

• Atomistic Molecular Dynamics simulation indicates considerable interaction between HCQ and COVID-19 protease.

• RMSD plot suggests complex formation between HCQ and COVID-19 protease after 2 ns.

• Equilibration of binding occurs between HCQ and COVID-19 protease between 7 and 10 ns.

• Binding with HCQ induced large structural change in COVID-19 protease, hence change in its activity.

Abstract

The present work is an investigation to test hydroxychloroquine as an inhibitor for the COVID-19 main protease. Molecular docking studies revealed a high docking score and interaction energies and decent level of docking within the cavity in protease moiety. Molecular dynamics simulations also lead to the evaluation of conformational energies, average H-bonding distance, RMSD plots etc. Large RMSD fluctuations for the first 2 ns seem to provide the conformational and rotational changes associated with the drug molecule when it comes into the vicinity on the protease matrix. Snapshots of structural changes with respect to time vividly indicates that drug molecule has a profound impact on the binding sites as well as overall geometry of the protease moiety. On the whole, hydroxyxhloroquine confers good inhibitory response to COVID-19 main protease. We hope the present study should help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus.