Show simple item record

dc.contributor.advisorBello García, Felio Jesús 
dc.contributor.advisorNeyts, Johan 
dc.creatorSegura Guerrero, Nidya Alexandra 
dc.date.accessioned2016-04-01T19:45:16Z
dc.date.available2016-04-01T19:45:16Z
dc.date.created2015-12-10
dc.date.issued2015
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/11891
dc.description.abstractDengue and Chikungunya viruses cause the most important arthropod-borne viral infections for humans. These viruses are predominant in tropical and subtropical regions. In addition, these viruses are predominant in tropical and subtropical regions. Dengue mortality rate is around 1.2 to 3.5% and deaths due to chikungunya fever are around 1 in 1000; however, half of chikungunya-infected patients evolve into a chronic state that can persist for months up to years. There are no antiviral drugs available for DENV and CHIKV treatment and prevention. Moreover, vector control strategies have failed so far. Thus, the development of potent inhibitors for a broad spectrum of RNA viruses is urgently needed. We established and characterized a new embryonic insect cell line from Culex quinquefasciatus mosquito. Also we established the flaviviruses and alphavirus replication, both in C6/36 and Lulo insect cell lines, as well as in Vero cell line. In addition we carried out a reference compound library and reference panel of assays and data for DENV, which provides a benchmark for further studies. During this study, a panel of 9 antiviral molecules, with proven in vitro anti-dengue virus activity and that act at different stages of the DENV life cycle, was selected. Finally, Favipiravir or T-705, was identified as inhibitor in vitro and in vivo of alphaviruses and the mutation K291R in nsP4, which is responsible of the polymerase activity, was found as the mode of action in CHIKV. Interestingly, lysine in motif F1 is also highly conserved in positive-stranded RNA viruses and this might explain the broad spectrum of T-705 antiviral activity.
dc.description.sponsorshipColciencias
dc.description.sponsorshipErasmus Mundus
dc.description.sponsorshipKU Leuven
dc.format.mimetypeapplication/pdf
dc.language.isospa
dc.sourceinstname:Universidad del Rosario
dc.sourcereponame:Repositorio Institucional EdocUR
dc.subject.ddcEnfermedades 
dc.subject.lembCultivo de células
dc.titleThe use of insect cells to identify potent and selective inhibitors of the replication of the Dengue and Chikungunya viruses and unravel their molecular mechanism of action
dc.typedoctoralThesis
dc.publisherUniversidad del Rosario
dc.creator.degreeDoctor en Ciencias Biomédicas
dc.publisher.programDoctorado en Ciencias Biomédicas
dc.publisher.departmentFacultad de Ciencias Naturales y Matemáticas
dc.subject.keywordFavipiravir
dc.subject.keywordDengue
dc.subject.keywordChikungunya
dc.subject.keywordCell culture
dc.subject.keywordMechanism of action
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.subject.decsDengue
dc.subject.decsVirus Chikungunya
dc.subject.decsControl de Vectores
dc.type.spaTesis de doctorado
dc.rights.accesoAbierto (Texto completo)
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion
dc.source.bibliographicCitationChen, L.H. & Wilson, M.E., 2010. Dengue and chikungunya infections in travelers. Current opinion in infectious diseases, 23(5), pp.438–44. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20581669 [Accessed July 10, 2013].
dc.source.bibliographicCitationEnserik, M., 2006. Massive Outbreak Draws Fresh Attention to Little-Known Virus. Science, 311(February), p.2006.
dc.source.bibliographicCitationManimunda, S.P. et al., 2010. Clinical progression of chikungunya fever during acute and chronic arthritic stages and the changes in joint morphology as revealed by imaging. Transactions of the Royal Society of Tropical Medicine and Hygiene, 104(6), pp.392–9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20171708 [Accessed October 4, 2012].
dc.source.bibliographicCitationOrganización Panamericana de la Salud, 2014. Número de casos reportados de chikungunya en países o territorios de las Américas 2013-2014 (por semana),
dc.source.bibliographicCitationPowers, A.M. et al., 2001. Evolutionary Relationships and Systematics of the Alphaviruses. Journal of virology, 75(21), pp.10118–10131.
dc.source.bibliographicCitationSolignat, M. et al., 2009. Replication cycle of chikungunya: A re-emerging arbovirus. Virology, 393(2), pp.183–197.
dc.rights.licenciaEL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DEL ROSARIO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. -------------------------------------- POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DEL ROSARIO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. Para el correcto ejercicio de mi derecho de habeas data cuento con la cuenta de correo habeasdata@urosario.edu.co, donde previa identificación podré solicitar la consulta, corrección y supresión de mis datos.


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record