Evolución molecular de Betacoronavirus zoonóticos asociados con el Síndrome de Distrés Respiratorio Agudo (SDRA)

dc.contributorBermúdez Santana, Clara Isabel
dc.contributorGallego Gómez, Juan Carlos
dc.contributorRNómica Teórica y Computacional
dc.creatorRojas Cruz, Alexis Felipe
dc.date.accessioned2022-06-23T16:18:25Z
dc.date.available2022-06-23T16:18:25Z
dc.date.created2022-06-23T16:18:25Z
dc.date.issued2022-06-20
dc.identifierhttps://repositorio.unal.edu.co/handle/unal/81628
dc.identifierUniversidad Nacional de Colombia
dc.identifierRepositorio Institucional Universidad Nacional de Colombia
dc.identifierhttps://repositorio.unal.edu.co/
dc.description.abstractLos Betacoronavirus han causado a su paso epidemias mortales, como el brote de SARS-CoV de 2002 y la continua prevalencia del MERS-CoV que se detectó por primera vez en 2012. A finales de 2019, se inició la pandemia de COVID-19, lo que impulsó a los científicos de todo el mundo a aplicar sus respectivos conocimientos para abordar cómo el SARS-CoV-2 infecta a los humanos. La principal estrategia ha sido la implementación de sistemas convencionales de vigilancia sanitaria para identificar, intervenir y controlar las infecciones virales causadas por estos virus emergentes. Aunque el seguimiento de la evolución genética del virus ha sido de gran importancia, se desconoce hasta qué punto es posible la transmisión zoonótica entre especies animales susceptibles y no susceptibles, así como la eventual funcionalidad de la arquitectura estructural del genoma de RNA de los Betacoronavirus en la fisiopatología, principalmente para SARS-CoV, MERS-CoV y SARS-CoV-2. Para llenar este vacío de conocimiento y facilitar el desarrollo de tratamientos eficaces, se realizó un estudio amplio de los genomas de los Betacoronavirus mediante el análisis de 1,252,952 secuencias virales reportadas en bases de datos que han circulado desde el 2002 pasando de reservorios naturales a huésped intermedio y humanos. Este trabajo considera dos enfoques diferentes de representar la información genómica, como se presentan y discuten en el capítulo 2: Análisis de secuencia. Esta parte del trabajo presenta un análisis evolutivo de transmisión horizontal en las secuencias virales para caracterizar y describir completamente la variación intra-hospedera de los Betacoronavirus. Los resultados revelan que cambios de aminoácidos en la subunidad S1 de la proteína S de SARS-CoV (G > T; A577S), MERS-CoV (C > T; S746R y C > T; N762A) y SARS-CoV-2 (A > G; D614G) con señales de selección positiva son factores fundamentales que subyacen al posible salto de barrera de los murciélagos al huésped intermedio. El capítulo 3: Análisis estructural, es una sección que explora los Betacoronavirus a nivel estructural como propuesta para descubrir si el plegamiento de estructuras secundarias de RNA conservadas podrían actuar como loci putativos para procesar RNAs pequeños virales, con una posible función asociada a la patogénesis en proceso de selección. Más del 87.58% de estas estructuras de RNA indican que 12 regiones portan RNAs pequeños en los Betacoronavirus, sugiriendo la posibilidad de modular la reprogramación transcripcional del nuevo huésped después de la infección. Los hallazgos de este estudio proporcionan una serie de significativos patrones moleculares que contribuyen a expandir las fronteras de la terapéutica humanos en el contexto de la actual crisis sanitaria mundial.
dc.description.abstractBetacoronavirus have caused earlier deadly epidemics, including the 2002 SARS-CoV outbreak and the ongoing prevalence of MERS-CoV, which was first detected in 2012. In late 2019, the emergence of the COVID-19 pandemic encouraged scientists around the globe to apply their respective insights to address how SARS-CoV-2 infects humans. The main strategy has been the implementation of standard health surveillance systems to identify, manage and control viral infections caused by these emerging viruses. Even though monitoring the genetic evolution of the virus has been of high significance, to what extent zoonotic transmission across susceptible and non-susceptible animal species is possible, as well as eventual functionality the structural architecture of the RNA genome of Betacoronavirus in the pathophysiology, mainly for SARS-CoV, MERS-CoV and SARS-CoV-2 is unclear. To fill this knowledge gap and facilitate the development of effective treatments, a comprehensive study of Betacoronavirus genomes was performed by means of the analysis of 1,252,952 viral sequences reported in databases which have circulated since 2002 from natural reservoirs to intermediate hosts and humans. This study includes two different approaches to represent genomic information, as introduced and discussed in Chapter 2: Sequence analyses. This part of the work represents an evolutionary analysis of horizontal transmission in viral sequences to thoroughly characterize and describe the intra-host variation and transmission routes of Betacoronavirus. The results reveal that amino acid changes within S protein S1 subunit of SARS-CoV (G > T; A577S), MERS-CoV (C > T; S746R and C > T; N762A) and SARS-CoV-2 (A > G; D614G) with signals of positive selection are pivotal factors underlying the possible jumping from bats barrier to intermediate host. Chapter 3: Structural analyses, is a section that explores Betacoronavirus at the structural level as a proposal to discover whether the folding of conserved RNA secondary structures may act as putative loci for processing virus-derived small RNAs, with a potential function associated with pathogenesis in the process of selection. Over 87.58% of these RNA structures indicate that 12 regions carry small RNAs in Betacoronavirus, suggesting the possibility of modulation of transcriptional re-programming of the new host upon infection. The findings of this study provide a collection of significant molecular signatures that contribute to pushing the frontiers of human therapeutics in the context of the current global health crisis.
dc.languagespa
dc.publisherUniversidad Nacional de Colombia
dc.publisherBogotá - Ciencias - Maestría en Ciencias - Biología
dc.publisherDepartamento de Biología
dc.publisherFacultad de Ciencias
dc.publisherBogotá, Colombia
dc.publisherUniversidad Nacional de Colombia - Sede Bogotá
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dc.rightsReconocimiento 4.0 Internacional
dc.rightshttp://creativecommons.org/licenses/by/4.0/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleEvolución molecular de Betacoronavirus zoonóticos asociados con el Síndrome de Distrés Respiratorio Agudo (SDRA)
dc.typeTrabajo de grado - Maestría


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