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High-Throughput Virtual Screening Lead to Discovery of Non-Peptidic Inhibitors of West Nile Virus NS3 Protease

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Computational Drug Discovery and Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 819))

Abstract

The non-structural 3 protease is an essential flaviviral enzyme and therefore one of the most promising targets for drug development against West Nile virus infections. In this chapter, we discuss in detail the computational methods used in the previous two docking campaigns which lead to the discovery of non-peptidic low micromolar inhibitors. Not only an X-ray structure but also an alternative conformation generated from molecular dynamic simulations is used in the in silico screening. Moreover, unique scoring schemes are developed based on the properties of the binding site of the protein.

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Acknowledgments

I thank Drs. Amedeo Caflisch and Dariusz Ekonomiuk for performing part of the computational work in the two docking studies and critical discussions, thank A. Widmer (Novartis Pharma, Basel) for providing a program for multiple linear regression and the molecular modeling program Wit!P, which was used for preparing the structures, and also thank OpenEye Scientific Software Inc. for providing Filter v2.0.1, which was used for preparing the library for docking.

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Authors and Affiliations

  1. Department of Biochemistry, University of Zurich, Zurich, Switzerland

    Danzhi Huang

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  1. Danzhi Huang
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Correspondence to Danzhi Huang .

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Editors and Affiliations

  1. University of Utah, 30 South 2000 East Rm 307, Salt Lake City, 84112-5820, California, USA

    Riccardo Baron

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Huang, D. (2012). High-Throughput Virtual Screening Lead to Discovery of Non-Peptidic Inhibitors of West Nile Virus NS3 Protease. In: Baron, R. (eds) Computational Drug Discovery and Design. Methods in Molecular Biology, vol 819. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-465-0_36

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  • DOI: https://doi.org/10.1007/978-1-61779-465-0_36

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-61779-464-3

  • Online ISBN: 978-1-61779-465-0

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