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

ArticleinMethods in molecular biology (Clifton, N.J.) 819:615-23 · January 2012with5 Reads
Impact Factor: 1.29 · DOI: 10.1007/978-1-61779-465-0_36 · Source: PubMed

    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.