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. 2020 Nov 5:1219:128595.
doi: 10.1016/j.molstruc.2020.128595. Epub 2020 Jun 2.

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

Nabajyoti Baildya  1 , Narendra Nath Ghosh  2 , Asoke P Chattopadhyay  1
Affiliations

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

Nabajyoti Baildya et al. J Mol Struct. .

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.

Keywords: COVID-19 main chain protease; Hydroxychloroquine; MD-Simulation; Molecular docking.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Docked structure of COVID-19 main protease with HCQ and their nearest neighbours.
Fig. 2
Fig. 2
Structure of COVID-19 protease and hydroxychloroquine after equilibration.
Fig. 3
Fig. 3
Root mean square deviation (RMSD) plot of receptor (protease) and ligand (drug) before docking and of receptor-ligand complex after docking (3a). RMSD plot of receptor alone before and after docking (3b).
Fig. 4
Fig. 4
Root Mean Square Fluctuations of the protease and its docked form with HCQ.
Fig. 5
Fig. 5
Structural change at different times (Fig. 5a–e), Fig. 5f contains two different structures at t = 0 ns and at t = 10 ns
See this image and copyright information in PMC

References

    1. Liu C., Jhou Q., Li Y., Garner L.V., Watkins S.P., Carter L.J., Smoot J., Gregg A.C., Daniels A.D., Jervey S., Albaiu D. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent. Sci. 2020;6:315–331. - PMC - PubMed
    1. Tyrrell D.A., Bynoe M.L. Cultivation of viruses from a high proportion of patients with colds. Lancet. 1966;1:76–77. - PubMed
    1. Khan J.S., McIntosh K. History and recent advances in coronavirus discovery. Pediatr. Infect. Dis. J. 2005;24:S223–S227. - PubMed
    1. Drosten C., Gunther S., Preiser W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348:1967–1976. - PubMed
    1. Ksiazek T.G., Erdman D., Goldsmith C.S. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348:1953–1966. - PubMed

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