Publication:
Discovery of antiviral molecules for dengue: in silico search and biological evaluation

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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.creatorMaldonado Rojas, Wilson
dc.creatorMontes Grajales, Diana Lucía
dc.creatorBertel Sevilla, Angela
dc.creatorWagner Döbler, Irene
dc.creatorSztajer, Helena
dc.creatorReck, Michael
dc.creatorFlechas Alarcón, María Camila
dc.creatorOcazionez, Raquel Elvira
dc.creatorOlivero Vebel, Jesús
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.accessioned2019-04-02T13:14:35Z
dc.date.available2019-04-02T13:14:35Z
dc.date.embargoEndinfo:eu-repo/date/embargoEnd/2024-01-31es_CO
dc.date.issued2014
dc.description.abstractBackground: Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS2B/NS3 protease complex is a target for designing specific antivirals due to its importance in viral replication and its high degree of conservation. Methods: NS2B/NS3 protease complex structural information was employed to find small molecules that can inhibit the activity of the enzyme complex. This inhibitory activity was probed with in vitro assays using a fluorescent substrateand the complex NS2B/NS3 obtained by recombinant DNA techniques, for testing the activity against dengue virus replication, HepG2 cells infected with dengue virus serotype 2 were used. Results: A total of 210,903 small molecules from PubChem were docked in silico to the NS2B/NS3 structure (PDB: 2FOM) to find molecules that could inhibit this protein complex. Five of the best 500 leading compounds, according to their affinity values (-11.6 and -13.5 kcal/mol), were purchased. The inhibitory protease activity on the recombinant protein and antiviral assays was tested. Conclusions: Chemicals CID54681617, CID54692801 and CID54715399 were strong inhibitors of NS2B/NS3, with IC50 values (μM) and percentages of viral titer reductions of 19.9, 79.9%; 17.5, 69.8%; and 9.1, 73.9 %, respectively. Multivariate methods applied to the molecular descriptors showed two compounds that were structurally different from other DENV inhibitors. General significance: This discovery opens new possibilities for obtaining drug candidates against Dengue virus.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.extent41 páginases_CO
dc.identifier.bibliographicCitationContiene77 referencias bibliográficas. Véase documento adjuntoes_CO
dc.identifier.urihttp://repositorio.colciencias.gov.co/handle/11146/34204
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.keywordDengue protease inhibitor
dc.subject.keywordNS2B/NS3 complex
dc.subject.keywordMolecular docking
dc.subject.keywordIn vitro inhibition
dc.subject.keywordInhibitory activity
dc.subject.lembDenguees_CO
dc.subject.lembVectores -- Insectoses_CO
dc.subject.lembVectores patógenoses_CO
dc.subject.lembPlantas medicinaleses_CO
dc.subject.spinesAceites esencialeses_CO
dc.subject.spinesBioquímica vegetales_CO
dc.subject.spinesBiología moleculares_CO
dc.subject.spinesTecnología químicaes_CO
dc.subject.spinesCatalizadoreses_CO
dc.titleDiscovery of antiviral molecules for dengue: in silico search and biological evaluationes_CO
dc.typeOtroses_CO
dc.type.driverinfo:eu-repo/semantics/other.generacióndecontenidoses_CO
dc.type.hasversioninfo:eu-repo/semantics/draftes_CO
dspace.entity.typePublication

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