| Literature DB >> 25564380 |
Lorena Ramos Freitas de Sousa1, Hongmei Wu2, Liliane Nebo3, João Batista Fernandes3, Maria Fátima das Graças Fernandes da Silva3, Werner Kiefer2, Manuel Kanitz4, Jochen Bodem5, Wibke E Diederich4, Tanja Schirmeister2, Paulo Cezar Vieira6.
Abstract
NS2B-NS3 is a serine protease of the Dengue virus considered a key target in the search for new antiviral drugs. In this study flavonoids were found to be inhibitors of NS2B-NS3 proteases of the Dengue virus serotypes 2 and 3 with IC50 values ranging from 15 to 44 μM. Agathisflavone (1) and myricetin (4) turned out to be noncompetitive inhibitors of dengue virus serotype 2 NS2B-NS3 protease with Ki values of 11 and 4.7 μM, respectively. Docking studies propose a binding mode of the flavonoids in a specific allosteric binding site of the enzyme. Analysis of biomolecular interactions of quercetin (5) with NT647-NHS-labeled Dengue virus serotype 3 NS2B-NS3 protease by microscale thermophoresis experiments, yielded a dissociation constant KD of 20 μM. Our results help to understand the mechanism of inhibition of the Dengue virus serine protease by flavonoids, which is essential for the development of improved inhibitors.Entities:
Keywords: Biflavone; Dengue virus; Flavonol; NS2B-NS3 protease
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Year: 2014 PMID： 25564380 DOI： 10.1016/j.bmc.2014.12.015
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641