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Comparative Molecular Field Analysis and Molecular Docking Studies on Quinolinone Derivatives Indicate Potential Hepatitis C Virus Inhibitors

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Abstract

Presently, there are no effective vaccines and anti-virals for the prevention and treatment of Hepatitis C virus infections and hence there is an urgent need to develop potent HCV inhibitors. In this study, we have carried out molecular docking, molecular dynamics and 3D-QSAR on heteroaryl 3-(1,1-dioxo-2H-(1,2,4)-benzothiadizin-3-yl)-4-hydroxy-2(1H)-quinolinone series using NS5B protein. Total of 41 quinolinone derivatives is used for molecular modeling study. The binding conformation and hydrogen bond interaction of the docked complexes were analyzed to model the inhibitors. We identified the molecule XXXV that had a higher affinity with NS5B. The molecular dynamics study confirmed the stability of the compound XXXV-NS5B complex. The developed CoMFA descriptors parameters, which were calculated using a test set of 13 compounds, were statistically significant. Our results will provide useful insights and lead to design potent anti-Hepatitis C virus molecules.

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Abbreviations

CoMFA:

Comparative Molecular Field Analysis

HCV:

Hepatitis C virus

NS5B:

Nonstructural protein 5B

ONC:

Optimal Number of Components

PDB:

Protein Data Bank

PLS:

Partial Least Square

QSAR:

Quantitative Structure Activity Relationship

SEE:

Standard Error of Estimate

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Acknowledgements

AA and SR thank Indian Council of Medical Research (ICMR), Government of India Agency for the Research Grant (IRIS ID: 2014-0099) and also thank the management of VIT for the facilities provided.

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  1. Medical and Biological Computing Laboratory, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, 632014, India

    Kullappan Malathi, Sudha Ramaiah & Anand Anbarasu

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  1. Kullappan Malathi
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  2. Sudha Ramaiah
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Correspondence to Anand Anbarasu.

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Malathi, K., Ramaiah, S. & Anbarasu, A. Comparative Molecular Field Analysis and Molecular Docking Studies on Quinolinone Derivatives Indicate Potential Hepatitis C Virus Inhibitors. Cell Biochem Biophys 77, 139–156 (2019). https://doi.org/10.1007/s12013-019-00867-4

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