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Open AccessArticle

Multiple Virtual Screening Strategies for the Discovery of Novel Compounds Active Against Dengue Virus: A Hit Identification Study

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Program in Bioinformatics and Computational Biology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
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Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
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Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
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Institute of Theoretical Chemistry, University of Vienna, 1090 Vienna, Austria
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Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
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Applied Medical Virology Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Biocatalyst and Environmental Biotechnology Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
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Author to whom correspondence should be addressed.
Sci. Pharm. 2020, 88(1), 2; https://doi.org/10.3390/scipharm88010002
Received: 13 November 2019 / Revised: 3 December 2019 / Accepted: 11 December 2019 / Published: 19 December 2019
Dengue infection is caused by a mosquito-borne virus, particularly in children, which may even cause death. No effective prevention or therapeutic agents to cure this disease are available up to now. The dengue viral envelope (E) protein was discovered to be a promising target for inhibition in several steps of viral infection. Structure-based virtual screening has become an important technique to identify first hits in a drug screening process, as it is possible to reduce the number of compounds to be assayed, allowing to save resources. In the present study, pharmacophore models were generated using the common hits approach (CHA), starting from trajectories obtained from molecular dynamics (MD) simulations of the E protein complexed with the active inhibitor, flavanone (FN5Y). Subsequently, compounds presented in various drug databases were screened using the LigandScout 4.2 program. The obtained hits were analyzed in more detail by molecular docking, followed by extensive MD simulations of the complexes. The highest-ranked compound from this procedure was then synthesized and tested on its inhibitory efficiency by experimental assays. View Full-Text
Keywords: dengue virus; envelope protein; fragment molecular orbital; molecular dynamics; pharmacophore-based screening dengue virus; envelope protein; fragment molecular orbital; molecular dynamics; pharmacophore-based screening
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Hengphasatporn, K.; Garon, A.; Wolschann, P.; Langer, T.; Yasuteru, S.; Huynh, T.N.; Chavasiri, W.; Saelee, T.; Boonyasuppayakorn, S.; Rungrotmongkol, T. Multiple Virtual Screening Strategies for the Discovery of Novel Compounds Active Against Dengue Virus: A Hit Identification Study. Sci. Pharm. 2020, 88, 2.

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