Publication:
Novel NS2B/NS3-protease dengue virus inhibitors

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col.comunidadvinculadaComunidad científica colombianaes_CO
col.contrato0572-2012es_CO
col.date.proyecto2018-01
col.programa.colcienciasProgramas de CT+I Ejecutados por Redes de Conocimientoes_CO
col.tipo.espGeneración de contenidos impresos, radiales, audiovisuales, multimedia, virtuales y Creative Commonses_CO
dc.coverage.spatialColombiaes_CO
dc.creatorCabarcas Montalvo, María
dc.creatorOlivero Vebel, Jesús
dc.creatorMontes Grajales, Diana Lucía
dc.creatorMaldonado Rojas, Wilson
dc.creatorBertel Sevilla, Angela
dc.creatorWagner Döbler, Irene
dc.creatorSztajer, Helena
dc.creatorReck, Michael
dc.creatorFlechas Alarcón, María Camila
dc.creatorOcazionez, Raquel Elvira
dc.creator.corporativoBio-Red-CO-CENIVAMes_CO
dc.creator.corporativoUniversidad Industrial de Santander, UISes_CO
dc.creator.corporativoUniversidad de Cartagena, Unicartagenaes_CO
dc.creator.mailjoliverov@unicartagena.edu.coes_CO
dc.date.accessioned2019-04-02T13:58:09Z
dc.date.available2019-04-02T13:58:09Z
dc.date.embargoEndinfo:eu-repo/date/embargoEnd/2024-01-31es_CO
dc.date.issued2014
dc.description.abstractDengue disease, caused by the virus of the same name, is expanding globally with an annual estimate of 390 million people infected. However, available antivirals have been ineffective. Therefore, the search of small-molecule therapeutic candidates is a recurrent practice. The dengue virus (DENV) NS2B/NS3 protease complex is a recognized target for the design of specific antivirals, due to its importance in the replication and high degree of sequence conservation. The aim of this research was to find molecules capable of inhibiting this protein complex. A total of 210,903 molecules, from the PubChem database, were docked in silico to the NS2B/NS3 crystallographic structure (PDB: 2FOM). The recombinant protease was expressed in E. coli and purified by affinity chromatography. Five of the best 500 leading compounds, according to the virtual screening affinity values (-11.6 and -13.5 kcal/mol), were purchased. The inhibitory activity of these molecules by the protease was evaluated in vitro, using the action of the recombinant enzyme on the Boc-Gly-Arg-Arg-AMC substrate (IC50), and antiviral assays for the detection of NS1 viral titles in infected human hepatocytes. Compounds CID54681617, CID54692801, and CID54715399 showed to be strong inhibitors of NS2B/NS3, with IC50 values (μM) and percentages of NS1 viral title reductions corresponding to 19.9, 79.9%; 17.5, 69.8%; 9.1, 73.9 %, respectively. Multivariate methods on molecular descriptors showed that two of these compounds are structurally different from DENV inhibitors reported by other authors. This discovery opens new possibilities to obtain drug candidates against Dengue.es_CO
dc.description.isprojectnoes_CO
dc.description.projectid5507-543-31904es_CO
dc.description.projectnamePrograma: Bioprospección y desarrollo de ingredientes naturales para las industrias cosmética, farmacéutica y de productos de aseo con base en la biodiversidad colombianaes_CO
dc.description.sponsorshipDepartamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colcienciases_CO
dc.formatpdfes_CO
dc.format.extent39 páginases_CO
dc.identifier.bibliographicCitationContiene 68 referencias bibliográficas. Véase documento adjuntoes_CO
dc.identifier.urihttp://repositorio.colciencias.gov.co/handle/11146/34215
dc.language.isoenges_CO
dc.relation.ispartofPrograma: Bioprospección y desarrollo de ingredientes naturales para las industrias cosmética, farmacéutica y de productos de aseo con base en la biodiversidad colombiana. La publicación completa está disponible en : <a href="http://repositorio.colciencias.gov.co/handle/11146/34163" target="blank">http://repositorio.colciencias.gov.co/handle/11146/34163</a>es_CO
dc.rightsinfo:eu-repo/semantics/embargoedAccesses_CO
dc.subject.keywordTrypsin-like serine protease inhibitor
dc.subject.keywordVirtual screening
dc.subject.keywordIn vitro protease assay
dc.subject.keywordFluorogenic peptide substrate
dc.subject.lembDenguees_CO
dc.subject.lembVectores -- Insectoses_CO
dc.subject.lembVectores patógenoses_CO
dc.subject.lembE. colies_CO
dc.subject.spinesBioquímica vegetales_CO
dc.subject.spinesCatalizadoreses_CO
dc.subject.spinesAceites esencialeses_CO
dc.titleNovel NS2B/NS3-protease dengue virus inhibitorses_CO
dc.typeOtroses_CO
dc.type.driverinfo:eu-repo/semantics/other.generacióndecontenidoses_CO
dc.type.hasversioninfo:eu-repo/semantics/allowedVersiones_CO
dspace.entity.typePublication

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