Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19

Ilustraciones a color, diagramas

Autores:
Hernández Bocanegra, Natalia Andrea
Tipo de recurso:
Fecha de publicación:
2024
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/86453
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/86453
https://repositorio.unal.edu.co/
Palabra clave:
570 - Biología::576 - Genética y evolución
Receptor ACE2 humano
región Spike
variante
linaje viral
Human ACE2 receptor
Spike región
variant
viral lineage
ACE2
Enzima convertidora de angiotensina
Spike
Covid-19
SARS-CoV-2
Rights
openAccess
License
Atribución-NoComercial 4.0 Internacional
id UNACIONAL2_4c89bddd96bcfd7932395dbdb7cc01ce
oai_identifier_str oai:repositorio.unal.edu.co:unal/86453
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19
dc.title.translated.eng.fl_str_mv Analysis of genetic variability in seven exons of the human ACE2 gene and its relationship with the SARS-CoV-2 lineage in a group of individuals diagnosed with COVID-19
title Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19
spellingShingle Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19
570 - Biología::576 - Genética y evolución
Receptor ACE2 humano
región Spike
variante
linaje viral
Human ACE2 receptor
Spike región
variant
viral lineage
ACE2
Enzima convertidora de angiotensina
Spike
Covid-19
SARS-CoV-2
title_short Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19
title_full Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19
title_fullStr Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19
title_full_unstemmed Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19
title_sort Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19
dc.creator.fl_str_mv Hernández Bocanegra, Natalia Andrea
dc.contributor.advisor.none.fl_str_mv Pinzón Velasco, Andrés Mauricio
dc.contributor.author.none.fl_str_mv Hernández Bocanegra, Natalia Andrea
dc.contributor.researchgroup.spa.fl_str_mv Bioinformática
dc.contributor.orcid.spa.fl_str_mv https://orcid.org/0009-0001-4161-6069
dc.subject.ddc.spa.fl_str_mv 570 - Biología::576 - Genética y evolución
topic 570 - Biología::576 - Genética y evolución
Receptor ACE2 humano
región Spike
variante
linaje viral
Human ACE2 receptor
Spike región
variant
viral lineage
ACE2
Enzima convertidora de angiotensina
Spike
Covid-19
SARS-CoV-2
dc.subject.proposal.spa.fl_str_mv Receptor ACE2 humano
región Spike
variante
linaje viral
dc.subject.proposal.eng.fl_str_mv Human ACE2 receptor
Spike región
variant
viral lineage
dc.subject.wikidata.none.fl_str_mv ACE2
Enzima convertidora de angiotensina
Spike
dc.subject.bne.none.fl_str_mv Covid-19
SARS-CoV-2
description Ilustraciones a color, diagramas
publishDate 2024
dc.date.accessioned.none.fl_str_mv 2024-07-16T15:25:52Z
dc.date.available.none.fl_str_mv 2024-07-16T15:25:52Z
dc.date.issued.none.fl_str_mv 2024
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/86453
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/86453
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.references.spa.fl_str_mv Abdullaev, A., Abdurakhimov, A., Mirakbarova, Z., Ibragimova, S., Tsoy, V., Nuriddinov, S., Dalimova, D., Turdikulova, S., & Abdurakhmonov, I. (2022). Genome sequence diversity of SARS-CoV-2 obtained from clinical samples in Uzbekistan. PLoS ONE, 17(6). https://doi.org/10.1371/JOURNAL.PONE.0270314
Álvarez-Díaz, D. A., Ruiz-Moreno, H. A., Zapata-Bedoya, S., Franco-Muñoz, C., Laiton-Donato, K., Ferro, C., Sepulveda, M. T. H., Pacheco-Montealegre, M., Walteros, D. M., Carrero-Galindo, L. C., & Mercado-Reyes, M. (2022). Clinical outcomes associated with Mu variant infection during the third epidemic peak of COVID-19 in Colombia. International Journal of Infectious Diseases, 125, 149–152. https://doi.org/10.1016/j.ijid.2022.10.028
Angulo-Aguado, M., Corredor-Orlandelli, D., Carrillo-Martínez, J. C., Gonzalez-Cornejo, M., Pineda-Mateus, E., Rojas, C., Triana-Fonseca, P., Contreras Bravo, N. C., Morel, A., Parra Abaunza, K., Restrepo, C. M., Fonseca-Mendoza, D. J., & Ortega-Recalde, O. (2022). Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population. Frontiers in Medicine, 9, 910098. https://doi.org/10.3389/FMED.2022.910098/FULL
Auton, A., Abecasis, G. R., Altshuler, D. M., Durbin, R. M., Bentley, D. R., Chakravarti, A., Clark, A. G., Donnelly, P., Eichler, E. E., Flicek, P., Gabriel, S. B., Gibbs, R. A., Green, E. D., Hurles, M. E., Knoppers, B. M., Korbel, J. O., Lander, E. S., Lee, C., Lehrach, H., … Schloss, J. A. (2015). A global reference for human genetic variation. Nature, 526(7571), 68. https://doi.org/10.1038/NATURE15393
Benetti, E., Tita, R., Spiga, O., Ciolfi, A., Birolo, G., Bruselles, A., Doddato, G., Giliberti, A., Marconi, C., Musacchia, F., Pippucci, T., Torella, A., Trezza, A., Valentino, F., Baldassarri, M., Brusco, A., Asselta, R., Bruttini, M., Furini, S., … Pinto, A. M. (2020). ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. European Journal of Human Genetics, 28(11), 1602–1614. https://doi.org/10.1038/s41431-020-0691-z
BigDye ® Terminator v3.1 Cycle Sequencing Kit Protocol. (2002).
Biti, R., French, R. F., Young, J., Bennetts, B., Stewart, G., & Liang, T. (1997). HIV-1 infection in an individual homozygous for the CCR5 deletion allele. Nature Medicine, 3(3), 252–253. https://doi.org/10.1038/NM0397-252
Caicedo, J. D., Cáceres, A., Arboleda-Bustos, C. E., Mahecha, M. F., Ortega, J., Arboleda, G., & Arboleda, H. (2019). Genetic variability analysis in a population from Bogota: Toards a haplotype map. Biomedica, 39(3). https://doi.org/10.7705/BIOMEDICA.4753
Candido, D. S., Claro, I. M., de Jesus, J. G., Souza, W. M., Moreira, F. R. R., Dellicour, S., Mellan, T. A., du Plessis, L., Pereira, R. H. M., Sales, F. C. S., Manuli, E. R., Thézé, J., Almeida, L., Menezes, M. T., Voloch, C. M., Fumagalli, M. J., Coletti, T. M., da Silva, C. A. M., Ramundo, M. S., … Faria, N. R. (2020). Evolution and epidemic spread of SARS-CoV-2 in Brazil. Science (New York, N.y.), 369(6508), 1255–1260. https://doi.org/10.1126/SCIENCE.ABD2161
Casalino, L., Gaieb, Z., Goldsmith, J. A., Hjorth, C. K., Dommer, A. C., Harbison, A. M., Fogarty, C. A., Barros, E. P., Taylor, B. C., Mclellan, J. S., Fadda, E., & Amaro, R. E. (2020). Beyond shielding: The roles of glycans in the SARS-CoV-2 spike protein. ACS Central Science, 6(10), 1722–1734. https://doi.org/10.1021/ACSCENTSCI.0C01056/SUPPL_FILE/OC0C01056_SI_006.ZIP
Castillo, A. E., Parra, B., Tapia, P., Acevedo, A., Lagos, J., Andrade, W., Arata, L., Leal, G., Barra, G., Tambley, C., Tognarelli, J., Bustos, P., Ulloa, S., Fasce, R., & Fernández, J. (2020). Phylogenetic analysis of the first four SARS‐CoV‐2 cases in Chile. Journal of Medical Virology, 92(9), 1562. https://doi.org/10.1002/JMV.25797
Centro para el control y la prevención de enfermedades. (n.d.). Clasificaciones y definiciones de las variantes del SARS-CoV-2.
Clinical Spectrum | COVID-19 Treatment Guidelines. (n.d.). Retrieved January 5, 2024, from https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/
Curtis, D. (2021). Variants in ACE2 and TMPRSS2 Genes Are Not Major Determinants of COVID-19 Severity in UK Biobank Subjects. Human Heredity, 85(2), 66–68. https://doi.org/10.1159/000515200
Deng, S. Q., & Peng, H. J. (2020). Characteristics of and public health responses to the coronavirus disease 2019 outbreak in China. In Journal of Clinical Medicine (Vol. 9, Issue 2). MDPI. https://doi.org/10.3390/jcm9020575
Devaux, C. A., Rolain, J. M., & Raoult, D. (2020). ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. In Journal of Microbiology, Immunology and Infection (Vol. 53, Issue 3, pp. 425–435). Elsevier Ltd. https://doi.org/10.1016/j.jmii.2020.04.015
Dieter, C., Brondani, L. de A., Leitão, C. B., Gerchman, F., Lemos, N. E., & Crispim, D. (2022). Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis. PLOS ONE, 17(7), e0270627. https://doi.org/10.1371/JOURNAL.PONE.0270627
Ellinghaus, D., Degenhardt, F., Bujanda, L., Buti, M., Albillos, A., Invernizzi, P., Fernández, J., Prati, D., Baselli, G., Asselta, R., Grimsrud, M. M., Milani, C., Aziz, F., Kässens, J., May, S., Wendorff, M., Wienbrandt, L., Uellendahl-Werth, F., Zheng, T., … Karlsen, T. H. (2020). Genomewide Association Study of Severe Covid-19 with Respiratory Failure. New England Journal of Medicine, 383(16), 1522–1534. https://doi.org/10.1056/NEJMoa2020283
Faria, N. R., Mellan, T. A., Whittaker, C., Claro, I. M., da Candido, D. S., Mishra, S., E Crispim, M. A., S Sales, F. C., Hawryluk, I., McCrone, J. T., G Hulswit, R. J., M Franco, L. A., Ramundo, M. S., de Jesus, J. G., Andrade, P. S., Coletti, T. M., Ferreira, G. M., M Silva, C. A., Manuli, E. R., … Sabino, E. C. (n.d.). Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. In Mélodie Monod (Vol. 25). http://pangolin.cog-uk.io
Fehr, A. R., & Perlman, S. (2015). Coronaviruses: An overview of their replication and pathogenesis. Coronaviruses: Methods and Protocols, 1282, 1–23. https://doi.org/10.1007/978-1-4939-2438-7_1/TABLES/2
GISAID - gisaid.org. (n.d.). Retrieved December 7, 2023, from https://gisaid.org/
Glowacka, I., Bertram, S., Müller, M. A., Allen, P., Soilleux, E., Pfefferle, S., Steffen, I., Tsegaye, T. S., He, Y., Gnirss, K., Niemeyer, D., Schneider, H., Drosten, C., & Pöhlmann, S. (2011a). Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response. Journal of Virology, 85(9), 4122–4134. https://doi.org/10.1128/jvi.02232-10
Gómez, S. A., Rojas-Valencia, N., Gómez, S., Cappelli, C., & Restrepo, A. (2021). The Role of Spike Protein Mutations in the Infectious Power of SARS-COV-2 Variants: A Molecular Interaction Perspective. Chembiochem : A European Journal of Chemical Biology. https://doi.org/10.1002/cbic.202100393
Gorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., Penzar, D., Perlman, S., M Poon, L. L., Samborskiy, D. V, Sidorov, I. A., Sola, I., & Ziebuhr, J. (n.d.). The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology. https://doi.org/10.1038/s41564-020-0695-z
Gorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., Penzar, D., Perlman, S., Poon, L. L. M., Samborskiy, D. V., Sidorov, I. A., Sola, I., & Ziebuhr, J. (2020). The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology, 5(4), 536–544. https://doi.org/10.1038/S41564-020-0695-Z
Gorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., Penzar, D., Perlman, S., Poon, L. L., Samborskiy, D., Sidorov, I. A., Sola, I., & Ziebuhr, J. (n.d.). Severe acute respiratory syndrome-related coronavirus: The species and its viruses-a statement of the Coronavirus Study Group. https://doi.org/10.1101/2020.02.07.937862
Gordon, D. E., Jang, G. M., Bouhaddou, M., Xu, J., Obernier, K., White, K. M., O’Meara, M. J., Rezelj, V. V., Guo, J. Z., Swaney, D. L., Tummino, T. A., Hüttenhain, R., Kaake, R. M., Richards, A. L., Tutuncuoglu, B., Foussard, H., Batra, J., Haas, K., Modak, M., … Krogan, N. J. (2020). A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583(7816), 459–468. https://doi.org/10.1038/s41586-020-2286-9
Greaney, A. J., Loes, A. N., Crawford, K. H. D., Starr, T. N., Malone, K. D., Chu, H. Y., & Bloom, J. D. (2021). Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host & Microbe, 29(3), 463. https://doi.org/10.1016/J.CHOM.2021.02.003
Hadfield, J., Megill, C., Bell, S. M., Huddleston, J., Potter, B., Callender, C., Sagulenko, P., Bedford, T., & Neher, R. A. (2018). NextStrain: Real-time tracking of pathogen evolution. Bioinformatics, 34(23), 4121–4123. https://doi.org/10.1093/BIOINFORMATICS/BTY407
Harrison, S. C. (2008). Viral membrane fusion. Nature Structural & Molecular Biology, 15(7), 690. https://doi.org/10.1038/NSMB.1456
Hernández, M., García-Morán, E., Abad, D., & Eiros, J. M. (n.d.). GISAID: INICIATIVA INTERNACIONAL PARA COMPARTIR DATOS GENÓMICOS DEL VIRUS DE LA GRIPE Y DEL SARS-CoV-2. Retrieved December 3, 2023, from www.mscbs.es/resp
Heurich, A., Hofmann-Winkler, H., Gierer, S., Liepold, T., Jahn, O., & Pöhlmann, S. (2014). TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein. Journal of Virology, 88(2), 1293–1307. https://doi.org/10.1128/JVI.02202-13
Hirotsu, Y., & Omata, M. (2021). Discovery of a SARS-CoV-2 variant from the P.1 lineage harboring K417T/E484K/N501Y mutations in Kofu, Japan. The Journal of Infection, 82(6), 276. https://doi.org/10.1016/J.JINF.2021.03.013
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052
Holmes, E. C., Goldstein, S. A., Rasmussen, A. L., Robertson, D. L., Crits-Christoph, A., Wertheim, J. O., Anthony, S. J., Barclay, W. S., Boni, M. F., Doherty, P. C., Farrar, J., Geoghegan, J. L., Jiang, X., Leibowitz, J. L., Neil, S. J. D., Skern, T., Weiss, S. R., Worobey, M., Andersen, K. G., … Rambaut, A. (n.d.). Leading Edge The origins of SARS-CoV-2: A critical review. https://doi.org/10.1016/j.cell.2021.08.017
Hu, B., Guo, H., Zhou, P., & Shi, Z.-L. (n.d.). Characteristics of SARS-CoV-2 and COVID-19. https://doi.org/10.1038/s41579-020-00459-7
Hwang, S. S., Lim, J., Yu, Z., Kong, P., Sefik, E., Xu, H., Harman, C. C. D., Kim, L. K., Lee, G. R., Li, H. B., & Flavell, R. A. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, N.y.), 367(6483), 1260. https://doi.org/10.1126/SCIENCE.ABB2507
Instituto Nacional de Salud. (n.d.). Coronavirus Colombia. Coronavirus Colombia. Retrieved January 26, 2024, from https://www.ins.gov.co/Noticias/Paginas/Coronavirus.aspx
Instituto Nacional de Salud | Colombia Documentos tecnicos genomica. (n.d.). Retrieved January 23, 2024, from https://www.ins.gov.co/Paginas/Documentos-tecnicos-genomica.aspx
Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E. E., Bhattacharya, T., Foley, B., Hastie, K. M., Parker, M. D., Partridge, D. G., Evans, C. M., Freeman, T. M., de Silva, T. I., Angyal, A., Brown, R. L., Carrilero, L., … Montefiori, D. C. (2020). Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell, 182(4), 812. https://doi.org/10.1016/J.CELL.2020.06.043
Kuja, J. O., Kanoi, B. N., Balboa, R. F., Shiluli, C., Maina, M., Waweru, H., Gathii, K., Mungai, M., Masika, M., Anzala, O., Mwau, M., Clark, T. G., Waitumbi, J., & Gitaka, J. (2022). Genomic surveillance of SARS-COV-2 reveals diverse circulating variant lineages in Nairobi and Kiambu Counties, Kenya. BMC Genomics, 23(1). https://doi.org/10.1186/S12864-022-08853-6
Laiton-Donato, K., Franco-Muñoz, C., Álvarez-Díaz, D. A., Ruiz-Moreno, H. A., Usme-Ciro, J. A., Prada, D. A., Reales-González, J., Corchuelo, S., Herrera-Sepúlveda, M. T., Naizaque, J., Santamaría, G., Rivera, J., Rojas, P., Ortiz, J. H., Cardona, A., Malo, D., Prieto-Alvarado, F., Gómez, F. R., Wiesner, M., … Mercado-Reyes, M. (2021). Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2. Infection, Genetics and Evolution, 95, 105038. https://doi.org/10.1016/J.MEEGID.2021.105038
Laiton-Donato, K., Usme-Ciro, J. A., Franco-Muñoz, C., Álvarez-Díaz, D. A., Ruiz-Moreno, H. A., Reales-González, J., Prada, D. A., Corchuelo, S., Herrera-Sepúlveda, M. T., Naizaque, J., Santamaría, G., Wiesner, M., Walteros, D. M., Ospina Martínez, M. L., & Mercado-Reyes, M. (2021a). Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K. Frontiers in Medicine, 8, 697605. https://doi.org/10.3389/FMED.2021.697605/FULL
Laiton-Donato, K., Usme-Ciro, J. A., Franco-Muñoz, C., Álvarez-Díaz, D. A., Ruiz-Moreno, H. A., Reales-González, J., Prada, D. A., Corchuelo, S., Herrera-Sepúlveda, M. T., Naizaque, J., Santamaría, G., Wiesner, M., Walteros, D. M., Ospina Martínez, M. L., & Mercado-Reyes, M. (2021b). Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K. Frontiers in Medicine, 8, 697605. https://doi.org/10.3389/FMED.2021.697605/FULL
Lan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., & Wang, X. (2020). Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 581(7807), 215–220. https://doi.org/10.1038/S41586-020-2180-5
Li, Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., Ren, R., Leung, K. S. M., Lau, E. H. Y., Wong, J. Y., Xing, X., Xiang, N., Wu, Y., Li, C., Chen, Q., Li, D., Liu, T., Zhao, J., Liu, M., … Feng, Z. (2020). Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. The New England Journal of Medicine, 382(13), 1199. https://doi.org/10.1056/NEJMOA2001316
Lieb, W., Graf, J., Götz, A., König, I. R., Mayer, B., Fischer, M., Stritzke, J., Hengstenberg, C., Holmer, S. R., Döring, A., Löwel, H., Schunkert, H., & Erdmann, J. (2006). Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg echocardiographic substudy. Journal of Molecular Medicine (Berlin, Germany), 84(1), 88–96. https://doi.org/10.1007/S00109-005-0718-5
Lorenzo-Redondo, R., Nam, H. H., Roberts, S. C., Simons, L. M., Jennings, L. J., Qi, C., Achenbach, C. J., Hauser, A. R., Ison, M. G., Hultquist, J. F., & Ozer, E. A. (n.d.). A Unique Clade of SARS-CoV-2 Viruses is Associated with Lower Viral Loads in Patient Upper Airways. https://doi.org/10.1101/2020.05.19.20107144
Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., … Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Www.Thelancet.Com, 395, 565. https://doi.org/10.1016/S0140-6736(20)30251-8
Martínez-Gómez, L. E., Herrera-López, B., Martinez-Armenta, C., Ortega-Peña, S., Camacho-Rea, M. del C., Suarez-Ahedo, C., Vázquez-Cárdenas, P., Vargas-Alarcón, G., Rojas-Velasco, G., Fragoso, J. M., Vidal-Vázquez, P., Ramírez-Hinojosa, J. P., Rodríguez-Sánchez, Y., Barrón-Díaz, D., Moreno, M. L., Martínez-Ruiz, F. de J., Zayago-Angeles, D. M., Mata-Miranda, M. M., Vázquez-Zapién, G. J., López-Reyes, A. (2022). ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men. Frontiers in Immunology, 13, 1. https://doi.org/10.3389/FIMMU.2022.812940/FULL
Medina-Enríquez, M. M., Lopez-León, S., Carlos-Escalante, J. A., Aponte-Torres, Z., Cuapio, A., & Wegman-Ostrosky, T. (2020). ACE2: the molecular doorway to SARS-CoV-2. In Cell and Bioscience (Vol. 10, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s13578-020-00519-8
Menachery, V. D., Yount, B. L., Debbink, K., Agnihothram, S., Gralinski, L. E., Plante, J. A., Graham, R. L., Scobey, T., Ge, X. Y., Donaldson, E. F., Randell, S. H., Lanzavecchia, A., Marasco, W. A., Shi, Z. L., & Baric, R. S. (2015). A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nature Medicine, 21(12), 1508–1513. https://doi.org/10.1038/nm.3985
Mio, C., Secco, C. D., Marzinotto, S., Pipan, C., Sozio, E., Tascini, C., Damante, G., & Curcio, F. (2022). Correspondence: Monitoring the SPREAD of the SARS-CoV-2 lineage B.1.621 in Udine, Italy. Journal of Clinical Pathology, 75(10), 712. https://doi.org/10.1136/JCLINPATH-2021-207810
Nextclade. (n.d.). Retrieved January 6, 2024, from https://clades.nextstrain.org/
Nieto-Torres, J. L., DeDiego, M. L., Verdiá-Báguena, C., Jimenez-Guardeño, J. M., Regla-Nava, J. A., Fernandez-Delgado, R., Castaño-Rodriguez, C., Alcaraz, A., Torres, J., Aguilella, V. M., & Enjuanes, L. (2014). Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis. PLoS Pathogens, 10(5). https://doi.org/10.1371/journal.ppat.1004077
Örd, M., Faustova, I., & Loog, M. (2020). The sequence at Spike S1/S2 site enables cleavage by furin and phospho-regulation in SARS-CoV2 but not in SARS-CoV1 or MERS-CoV. Scientific Reports 2020 10:1, 10(1), 1–10. https://doi.org/10.1038/s41598-020-74101-0
Organizaciòn mundial de la salud. (n.d.). Panel de control de la OMS sobre el coronavirus (COVID-19).
Organization, W. H. (2021). WHO-convened global study of origins of SARS-CoV-2: China part.
Park, S. T., & Kim, J. (2016). Trends in Next-Generation Sequencing and a New Era for Whole Genome Sequencing. International Neurourology Journal, 20(Suppl 2), S76. https://doi.org/10.5213/INJ.1632742.371
Pekar, J. E., Magee, A., Parker, E., Moshiri, N., Izhikevich, K., Havens, J. L., Gangavarapu, K., Mariana, L., Serrano, M., Crits-Christoph, A., Matteson, N. L., Zeller, M., Levy, J. I., Wang, J. C., Hughes, S., Lee, J., Ching, K., Yan, Z., Tzer, R., … Wertheim, J. O. (n.d.). The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. https://www.science.org
Primer3. (n.d.). Retrieved January 5, 2024, from https://primer3.org/
Propuestas aprobadas | ICTV. (n.d.). Retrieved December 8, 2023, from https://ictv.global/files/proposals/approved?fid=4929
Quintana-Murci, L. (2016). Genetic and epigenetic variation of human populations: An adaptive tale. Comptes Rendus Biologies, 339(7–8), 278–283. https://doi.org/10.1016/J.CRVI.2016.04.005
Rambaut, A., Holmes, E. C., OToole, Á., Hill, V., McCrone, J. T., Ruis, C., du Plessis, L., & Pybus, O. G. (n.d.). A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nature Microbiology. https://doi.org/10.1038/s41564-020-0770-5
Ravi, V., Saxena, S., & Panda, P. S. (2022). Basic virology of SARS-CoV 2. Indian Journal of Medical Microbiology, 40(2), 182. https://doi.org/10.1016/J.IJMMB.2022.02.005
Rivero, R., Garay, E., Botero, Y., Serrano-Coll, H., Gastelbondo, B., Muñoz, M., Ballesteros, N., Castañeda, S., Patiño, L. H., Ramirez, J. D., Calderon, A., Guzmán, C., Martinez-Bravo, C., Aleman, A., Arrieta, G., & Mattar, S. (2022). Human-to-dog transmission of SARS-CoV-2, Colombia. Scientific Reports, 12(1). https://doi.org/10.1038/S41598-022-11847-9
Sabater Molina, M., Nicolás Rocamora, E., Bendicho, A. I., Vázquez, E. G., Zorio, E., Rodriguez, F. D., Gil Ortuño, C., Rodríguez, A. I., Sánchez-López, A. J., Jara Rubio, R., Moreno-Docón, A., Marcos, P. J., García Pavía, P., Villa, R. B., & Gimeno Blanes, J. R. (2022). Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease. PloS One, 17(2), e0263140. https://doi.org/10.1371/JOURNAL.PONE.0263140
Sahajpal, V., Rajput, S., Sharma, T., Sharma, A., & Thakar, M. K. (2019). Development and evaluation of a novel DNA purification buffer and protocol for blood samples on FTA cards. Forensic Science International: Reports, 1, 100014. https://doi.org/10.1016/J.FSIR.2019.100014
Secuenciación genómica y caracterización genética del virus de la influenza | CDC. (n.d.). Retrieved January 27, 2024, from https://espanol.cdc.gov/flu/about/professionals/genetic-characterization.htm
Secuenciacion-genoma-completo-SARS-COV-2-secuenciador-MINION. (n.d.).
Senapati, S., Banerjee, P., Bhagavatula, S., Kushwaha, P. P., & Kumar, S. (2021). Contributions of human ACE2 and TMPRSS2 in determining host–pathogen interaction of COVID-19. In Journal of Genetics (Vol. 100, Issue 1). Springer. https://doi.org/10.1007/s12041-021-01262-w
Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020a). Structural basis of receptor recognition by SARS-CoV-2. Nature 2020 581:7807, 581(7807), 221–224. https://doi.org/10.1038/s41586-020-2179-y
Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020b). Structural basis of receptor recognition by SARS-CoV-2. Nature, 581(7807), 221. https://doi.org/10.1038/S41586-020-2179-Y
Shovlin, C. L., & Vizcaychipi, M. P. (2020). COVID-19 genomic susceptibility: Definition of ACE2 variants relevant to human infection with SARS-CoV-2 in the context of ACMG/AMP Guidance. MedRxiv, 2020.05.12.20098160. https://doi.org/10.1101/2020.05.12.20098160
Siddell, S. G., Walker, P. J., Lefkowitz, E. J., Mushegian, A. R., Adams, M. J., Dutilh, B. E., Gorbalenya, A. E., Harrach, B., Harrison, R. L., Junglen, S., Knowles, N. J., Kropinski, A. M., Krupovic, M., Kuhn, J. H., Nibert, M., Rubino, L., Sabanadzovic, S., Sanfaçon, H., Simmonds, P., … Davison, A. J. (2019). Additional changes to taxonomy ratified in a special vote by the International Committee on Taxonomy of Viruses (October 2018). Archives of Virology, 164(3), 943–946. https://doi.org/10.1007/S00705-018-04136-2
Simmons, G., Gosalia, D. N., Rennekamp, A. J., Reeves, J. D., Diamond, S. L., & Bates, P. (2005). Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proceedings of the National Academy of Sciences of the United States of America, 102(33), 11876. https://doi.org/10.1073/PNAS.0505577102
Simmons, G., Zmora, P., Gierer, S., Heurich, A., & Pöhlmann, S. (2013). Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research. Antiviral Research, 100(3), 605. https://doi.org/10.1016/J.ANTIVIRAL.2013.09.028
Singh, D., & Yi, S. V. (2021). On the origin and evolution of SARS-CoV-2. Experimental & Molecular Medicine, 53, 537–547. https://doi.org/10.1038/s12276-021-00604-z
Situación del SARS CoV2 - Región de las Américas - OPS/OMS | Organización Panamericana de la Salud. (n.d.). Retrieved January 13, 2024, from https://www.paho.org/en/covid-19-weekly-updates-region-americas
Sun, P., Lu, X., Xu, C., Sun, W., & Pan, B. (2020). Understanding of COVID-19 based on current evidence. Journal of Medical Virology, 92(6), 548–551. https://doi.org/10.1002/JMV.25722
Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., Mlisana, K., von Gottberg, A., Walaza, S., Allam, M., Ismail, A., Mohale, T., Glass, A. J., Engelbrecht, S., Van Zyl, G., … de Oliveira, T. (2021). Detection of a SARS-CoV-2 variant of concern in South Africa. Nature, 592(7854), 438–443. https://doi.org/10.1038/S41586-021-03402-9
The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. (2020). European Journal of Human Genetics, 28(6), 715–718. https://doi.org/10.1038/s41431-020-0636-6
Thomas, S. (2021). Mapping the Nonstructural Transmembrane Proteins of Severe Acute Respiratory Syndrome Coronavirus 2. Journal of Computational Biology, 28(9), 909–921. https://doi.org/10.1089/cmb.2020.0627
Torre-Fuentes, L., Matías-Guiu, J., Hernández-Lorenzo, L., Montero-Escribano, P., Pytel, V., Porta-Etessam, J., Gómez-Pinedo, U., & Matías-Guiu, J. A. (2021). ACE2, TMPRSS2, and Furin variants and SARS-CoV-2 infection in Madrid, Spain. Journal of Medical Virology, 93(2), 863–869. https://doi.org/10.1002/jmv.26319
Tortorici, M. A., & Veesler, D. (2019). Structural insights into coronavirus entry. In Advances in Virus Research (Vol. 105, pp. 93–116). Academic Press Inc. https://doi.org/10.1016/bs.aivir.2019.08.002
(US), N. I. of H., & Study, B. S. C. (2007). Understanding Human Genetic Variation. https://www.ncbi.nlm.nih.gov/books/NBK20363/
Vadgama, N., Kreymerman, A., Campbell, J., Shamardina, O., Brugger, C., Research Consortium, G. E., Deaconescu, A. M., Lee, R. T., Penkett, C. J., Gifford, C. A., Mercola, M., Nasir, J., & Karakikes, I. (2022). SARS-CoV-2 Susceptibility and ACE2 Gene Variations Within Diverse Ethnic Backgrounds. Frontiers in Genetics, 13, 888025. https://doi.org/10.3389/FGENE.2022.888025/BIBTEX
Volz, E., Mishra, S., Chand, M., Barrett, J. C., Johnson, R., Geidelberg, L., Hinsley, W. R., Laydon, D. J., Dabrera, G., O’Toole, Á., Amato, R., Ragonnet-Cronin, M., Harrison, I., Jackson, B., Ariani, C. V., Boyd, O., Loman, N. J., McCrone, J. T., Gonçalves, S., … Ferguson, N. M. (2021). Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature, 593(7858), 266–269. https://doi.org/10.1038/S41586-021-03470-X
Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020). Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell, 181(2), 281. https://doi.org/10.1016/J.CELL.2020.02.058
Wang, N., Li, S. Y., Yang, X. Lou, Huang, H. M., Zhang, Y. J., Guo, H., Luo, C. M., Miller, M., Zhu, G., Chmura, A. A., Hagan, E., Zhou, J. H., Zhang, Y. Z., Wang, L. F., Daszak, P., & Shi, Z. L. (2018). Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China. Virologica Sinica, 33(1), 104. https://doi.org/10.1007/S12250-018-0012-7
WHO COVID-19 weekly epidemiological update vol. 74... - Google Académico. (n.d.). Retrieved January 2, 2024, from https://scholar.google.com/scholar?q=WHO+COVID-19+weekly+epidemiological+update+vol.+74+January+2022+World+Health+organization+
Wolf, J. M., Wolf, L. M., Bello, G. L., Maccari, J. G., & Nasi, L. A. (2023). Molecular evolution of SARS‐CoV‐2 from December 2019 to August 2022. Journal of Medical Virology, 95(1). https://doi.org/10.1002/JMV.28366
Wong, S. K., Li, W., Moore, M. J., Choe, H., & Farzan, M. (2004). A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2. Journal of Biological Chemistry, 279(5), 3197–3201. https://doi.org/10.1074/jbc.C300520200
Wu, C. rong, Yin, W. chao, Jiang, Y., & Xu, H. E. (2022). Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19. In Acta Pharmacologica Sinica (Vol. 43, Issue 12, pp. 3021–3033). Springer Nature. https://doi.org/10.1038/s41401-021-00851-w
Wu, F., Zhao, S., Yu, B., Chen, Y.-M., Wang, W., Song, Z.-G., Hu, Y., Tao, Z.-W., Tian, J.-H., Pei, Y.-Y., Yuan, M.-L., Zhang, Y.-L., Dai, F.-H., Liu, Y., Wang, Q.-M., Zheng, J.-J., Xu, L., Holmes, E. C., & Zhang, Y.-Z. (2008). A new coronavirus associated with human respiratory disease in China. Nature, 579. https://doi.org/10.1038/s41586-020-2008-3
Xiao, X., Newman, C., Buesching, C. D., Macdonald, D. W., & Zhou, Z.-M. (123 C.E.). Animal sales from Wuhan wet markets immediately prior to the COVID-19 pandemic. Scientific Reports |, 11, 11898. https://doi.org/10.1038/s41598-021-91470-2
Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C. R., Xia, H., Swanson, K. A., Cutler, M., Cooper, D., Menachery, V. D., Weaver, S. C., Dormitzer, P. R., & Shi, P. Y. (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature Medicine, 27(4), 620–621. https://doi.org/10.1038/S41591-021-01270-4
Yadav, R., Chaudhary, J. K., Jain, N., Chaudhary, P. K., Khanra, S., Dhamija, P., Sharma, A., Kumar, A., & Handu, S. (2021). cells Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19. 10, 821. https://doi.org/10.3390/cells
Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y., & Zhou, Q. (2020). Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. In Science (Vol. 367).
Yang, J., Petitjean, S. J. L., Koehler, M., Zhang, Q., Dumitru, A. C., Chen, W., Derclaye, S., Vincent, S. P., Soumillion, P., & Alsteens, D. (2020). Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-18319-6
Yoshimoto, F. K. (1234). The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. The Protein Journal, 39, 198–216. https://doi.org/10.1007/s10930-020-09901-4
Zeberg, H., & Pääbo, S. (2020). The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature 2020 587:7835, 587(7835), 610–612. https://doi.org/10.1038/s41586-020-2818-3
Zhu, L., Marsh, J. W., Griffith, M. P., Collins, K., Srinivasa, V., Waggle, K., Van Tyne, D., Snyder, G. M., Phan, T., Wells, A., Marroquin, O. C., & Harrison, L. H. (2022). Predictive model for severe COVID-19 using SARS-CoV-2 whole-genome sequencing and electronic health record data, March 2020-May 2021. PLoS ONE, 17(7). https://doi.org/10.1371/JOURNAL.PONE.0271381
Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., Niu, P., Zhan, F., Ma, X., Wang, D., Xu, W., Wu, G., Gao, G. F., Tan, W., & China Novel Coronavirus Investigating and Research Team. (2020). A Novel Coronavirus from Patients with Pneumonia in China, 2019. The New England Journal of Medicine, 382(8), 727–733. https://doi.org/10.1056/NEJMoa2001017
Glowacka, I., Bertram, S., Müller, M. A., Allen, P., Soilleux, E., Pfefferle, S., Steffen, I., Tsegaye, T. S., He, Y., Gnirss, K., Niemeyer, D., Schneider, H., Drosten, C., & Pöhlmann, S. (2011b). Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response. Journal of Virology, 85(9), 4122–4134. https://doi.org/10.1128/JVI.02232-10
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.license.spa.fl_str_mv Atribución-NoComercial 4.0 Internacional
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv Atribución-NoComercial 4.0 Internacional
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv viii, 71 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.coverage.temporal.none.fl_str_mv 2020-2021
dc.coverage.city.none.fl_str_mv Bogotá, Colombia
dc.publisher.spa.fl_str_mv Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv Bogotá - Ciencias - Maestría en Ciencias - Microbiología
dc.publisher.faculty.spa.fl_str_mv Facultad de Ciencias
dc.publisher.place.spa.fl_str_mv Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv Universidad Nacional de Colombia - Sede Bogotá
institution Universidad Nacional de Colombia
bitstream.url.fl_str_mv https://repositorio.unal.edu.co/bitstream/unal/86453/1/license.txt
https://repositorio.unal.edu.co/bitstream/unal/86453/2/1030666404.2024.pdf
https://repositorio.unal.edu.co/bitstream/unal/86453/3/1030666404.2024.pdf.jpg
bitstream.checksum.fl_str_mv eb34b1cf90b7e1103fc9dfd26be24b4a
194bcde4506763c6ad73fd6f45efd53d
4df2a62f88cd2b5ade038a7f5a3f48a6
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
repository.mail.fl_str_mv repositorio_nal@unal.edu.co
_version_ 1814089253974441984
spelling Atribución-NoComercial 4.0 Internacionalinfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Pinzón Velasco, Andrés Mauricio366c2eddf6aa24434ee55e57da235448Hernández Bocanegra, Natalia Andreaca6fc7d8b6afea7694b18a21e26548d4Bioinformáticahttps://orcid.org/0009-0001-4161-60692020-2021Bogotá, Colombia2024-07-16T15:25:52Z2024-07-16T15:25:52Z2024https://repositorio.unal.edu.co/handle/unal/86453Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/Ilustraciones a color, diagramasThe interaction between the Spike protein of SARS-CoV-2 and the human ACE2 receptor plays a pivotal role in the development of COVID-19. This study aimed to assess the genetic variability of the viral lineage and seven exons of the human ACE2 gene, along with analyzing clinical backgrounds and sociodemographic conditions related to susceptibility and disease severity. Using sequencing technology, samples from nasopharyngeal swabs were examined for the viral genome, and blood samples from 50 individuals diagnosed with SARS-CoV-2 infection or viral pneumonia were sequenced. Although no statistically significant associations were found between viral lineages and disease severity, it was observed that the B.1.621 lineage predominated in mild cases, while the B.1.420 lineage was present in moderate cases, and the P.1 lineage was found in both moderate and severe individuals. Analysis of exonic sequences of the ACE2 gene revealed a homozygous variant in exon 17, involving a synonymous substitution at position 133, resulting in the encoding of valine. No significant associations were found between demographic data, clinical history, and disease severity. These results indicate genetic variability in the studied regions of the ACE2 gene, underscoring the importance of future large-scale studies with representative samples to comprehend the virus's pathophysiology and its relationship with the developed phenotype.La interacción entre la proteína Spike del SARS-CoV-2 y el receptor ACE2 humano es crucial en el desarrollo de la enfermedad COVID-19. Este estudio buscó evaluar la variabilidad genética del linaje viral y de siete exones del gen ACE2 humano, así como analizar antecedentes clínicos y condiciones sociodemográficas relacionadas con la susceptibilidad y severidad de la enfermedad. Utilizando tecnología de secuenciación, se examinaron muestras de hisopado nasofaríngeo para el genoma viral y muestras sanguíneas de 50 individuos diagnosticados con infección o neumonía viral por SARS-CoV-2. Estos individuos fueron ingresados a la Clínica Universitaria Colombia, ubicada en la ciudad de Bogotá, desde octubre del año 2020 a junio del año 2021, y se clasificaron en tres grupos de severidad según los síntomas, el diagnóstico, la insuficiencia respiratoria y la necesidad de ventilación como: leve, moderado y severo. A pesar de no encontrar asociaciones estadísticamente significativas entre los linajes virales y la gravedad de la enfermedad, se observó que el linaje B.1.621 predomina en casos leves, mientras que el linaje B.1.420 está presente solo en casos moderados y el linaje P.1 se encontró en individuos moderados y severos. El análisis de las secuencias de los siete exones del gen ACE2 reveló una única variante homocigota en el exón 17; que corresponde a la sustitución de una guanina (G) por una adenina (A), causando un cambio sinónimo en la posición 748 de la proteína ACE2 que resulta en la codificación de una valina. No se encontraron correlaciones significativamente estadísticas entre datos demográficos, antecedentes clínicos y gravedad de la enfermedad. Se requieren estudios futuros con muestras representativas para comprender la fisiopatología del virus y su relación con el fenotipo desarrollado. (Texto tomado de la fuente)MaestríaBiología molecular de agentes infecciososviii, 71 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - MicrobiologíaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::576 - Genética y evoluciónReceptor ACE2 humanoregión Spikevariantelinaje viralHuman ACE2 receptorSpike regiónvariantviral lineageACE2Enzima convertidora de angiotensinaSpikeCovid-19SARS-CoV-2Análisis de la variabilidad genética en siete exones del gen ACE2 humano y su relación con el linaje de SARS-CoV-2 en un grupo de individuos diagnosticados con COVID-19Analysis of genetic variability in seven exons of the human ACE2 gene and its relationship with the SARS-CoV-2 lineage in a group of individuals diagnosed with COVID-19Trabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAbdullaev, A., Abdurakhimov, A., Mirakbarova, Z., Ibragimova, S., Tsoy, V., Nuriddinov, S., Dalimova, D., Turdikulova, S., & Abdurakhmonov, I. (2022). Genome sequence diversity of SARS-CoV-2 obtained from clinical samples in Uzbekistan. PLoS ONE, 17(6). https://doi.org/10.1371/JOURNAL.PONE.0270314Álvarez-Díaz, D. A., Ruiz-Moreno, H. A., Zapata-Bedoya, S., Franco-Muñoz, C., Laiton-Donato, K., Ferro, C., Sepulveda, M. T. H., Pacheco-Montealegre, M., Walteros, D. M., Carrero-Galindo, L. C., & Mercado-Reyes, M. (2022). Clinical outcomes associated with Mu variant infection during the third epidemic peak of COVID-19 in Colombia. International Journal of Infectious Diseases, 125, 149–152. https://doi.org/10.1016/j.ijid.2022.10.028Angulo-Aguado, M., Corredor-Orlandelli, D., Carrillo-Martínez, J. C., Gonzalez-Cornejo, M., Pineda-Mateus, E., Rojas, C., Triana-Fonseca, P., Contreras Bravo, N. C., Morel, A., Parra Abaunza, K., Restrepo, C. M., Fonseca-Mendoza, D. J., & Ortega-Recalde, O. (2022). Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population. Frontiers in Medicine, 9, 910098. https://doi.org/10.3389/FMED.2022.910098/FULLAuton, A., Abecasis, G. R., Altshuler, D. M., Durbin, R. M., Bentley, D. R., Chakravarti, A., Clark, A. G., Donnelly, P., Eichler, E. E., Flicek, P., Gabriel, S. B., Gibbs, R. A., Green, E. D., Hurles, M. E., Knoppers, B. M., Korbel, J. O., Lander, E. S., Lee, C., Lehrach, H., … Schloss, J. A. (2015). A global reference for human genetic variation. Nature, 526(7571), 68. https://doi.org/10.1038/NATURE15393Benetti, E., Tita, R., Spiga, O., Ciolfi, A., Birolo, G., Bruselles, A., Doddato, G., Giliberti, A., Marconi, C., Musacchia, F., Pippucci, T., Torella, A., Trezza, A., Valentino, F., Baldassarri, M., Brusco, A., Asselta, R., Bruttini, M., Furini, S., … Pinto, A. M. (2020). ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. European Journal of Human Genetics, 28(11), 1602–1614. https://doi.org/10.1038/s41431-020-0691-zBigDye ® Terminator v3.1 Cycle Sequencing Kit Protocol. (2002).Biti, R., French, R. F., Young, J., Bennetts, B., Stewart, G., & Liang, T. (1997). HIV-1 infection in an individual homozygous for the CCR5 deletion allele. Nature Medicine, 3(3), 252–253. https://doi.org/10.1038/NM0397-252Caicedo, J. D., Cáceres, A., Arboleda-Bustos, C. E., Mahecha, M. F., Ortega, J., Arboleda, G., & Arboleda, H. (2019). Genetic variability analysis in a population from Bogota: Toards a haplotype map. Biomedica, 39(3). https://doi.org/10.7705/BIOMEDICA.4753Candido, D. S., Claro, I. M., de Jesus, J. G., Souza, W. M., Moreira, F. R. R., Dellicour, S., Mellan, T. A., du Plessis, L., Pereira, R. H. M., Sales, F. C. S., Manuli, E. R., Thézé, J., Almeida, L., Menezes, M. T., Voloch, C. M., Fumagalli, M. J., Coletti, T. M., da Silva, C. A. M., Ramundo, M. S., … Faria, N. R. (2020). Evolution and epidemic spread of SARS-CoV-2 in Brazil. Science (New York, N.y.), 369(6508), 1255–1260. https://doi.org/10.1126/SCIENCE.ABD2161Casalino, L., Gaieb, Z., Goldsmith, J. A., Hjorth, C. K., Dommer, A. C., Harbison, A. M., Fogarty, C. A., Barros, E. P., Taylor, B. C., Mclellan, J. S., Fadda, E., & Amaro, R. E. (2020). Beyond shielding: The roles of glycans in the SARS-CoV-2 spike protein. ACS Central Science, 6(10), 1722–1734. https://doi.org/10.1021/ACSCENTSCI.0C01056/SUPPL_FILE/OC0C01056_SI_006.ZIPCastillo, A. E., Parra, B., Tapia, P., Acevedo, A., Lagos, J., Andrade, W., Arata, L., Leal, G., Barra, G., Tambley, C., Tognarelli, J., Bustos, P., Ulloa, S., Fasce, R., & Fernández, J. (2020). Phylogenetic analysis of the first four SARS‐CoV‐2 cases in Chile. Journal of Medical Virology, 92(9), 1562. https://doi.org/10.1002/JMV.25797Centro para el control y la prevención de enfermedades. (n.d.). Clasificaciones y definiciones de las variantes del SARS-CoV-2.Clinical Spectrum | COVID-19 Treatment Guidelines. (n.d.). Retrieved January 5, 2024, from https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/Curtis, D. (2021). Variants in ACE2 and TMPRSS2 Genes Are Not Major Determinants of COVID-19 Severity in UK Biobank Subjects. Human Heredity, 85(2), 66–68. https://doi.org/10.1159/000515200Deng, S. Q., & Peng, H. J. (2020). Characteristics of and public health responses to the coronavirus disease 2019 outbreak in China. In Journal of Clinical Medicine (Vol. 9, Issue 2). MDPI. https://doi.org/10.3390/jcm9020575Devaux, C. A., Rolain, J. M., & Raoult, D. (2020). ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. In Journal of Microbiology, Immunology and Infection (Vol. 53, Issue 3, pp. 425–435). Elsevier Ltd. https://doi.org/10.1016/j.jmii.2020.04.015Dieter, C., Brondani, L. de A., Leitão, C. B., Gerchman, F., Lemos, N. E., & Crispim, D. (2022). Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis. PLOS ONE, 17(7), e0270627. https://doi.org/10.1371/JOURNAL.PONE.0270627Ellinghaus, D., Degenhardt, F., Bujanda, L., Buti, M., Albillos, A., Invernizzi, P., Fernández, J., Prati, D., Baselli, G., Asselta, R., Grimsrud, M. M., Milani, C., Aziz, F., Kässens, J., May, S., Wendorff, M., Wienbrandt, L., Uellendahl-Werth, F., Zheng, T., … Karlsen, T. H. (2020). Genomewide Association Study of Severe Covid-19 with Respiratory Failure. New England Journal of Medicine, 383(16), 1522–1534. https://doi.org/10.1056/NEJMoa2020283Faria, N. R., Mellan, T. A., Whittaker, C., Claro, I. M., da Candido, D. S., Mishra, S., E Crispim, M. A., S Sales, F. C., Hawryluk, I., McCrone, J. T., G Hulswit, R. J., M Franco, L. A., Ramundo, M. S., de Jesus, J. G., Andrade, P. S., Coletti, T. M., Ferreira, G. M., M Silva, C. A., Manuli, E. R., … Sabino, E. C. (n.d.). Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. In Mélodie Monod (Vol. 25). http://pangolin.cog-uk.ioFehr, A. R., & Perlman, S. (2015). Coronaviruses: An overview of their replication and pathogenesis. Coronaviruses: Methods and Protocols, 1282, 1–23. https://doi.org/10.1007/978-1-4939-2438-7_1/TABLES/2GISAID - gisaid.org. (n.d.). Retrieved December 7, 2023, from https://gisaid.org/Glowacka, I., Bertram, S., Müller, M. A., Allen, P., Soilleux, E., Pfefferle, S., Steffen, I., Tsegaye, T. S., He, Y., Gnirss, K., Niemeyer, D., Schneider, H., Drosten, C., & Pöhlmann, S. (2011a). Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response. Journal of Virology, 85(9), 4122–4134. https://doi.org/10.1128/jvi.02232-10Gómez, S. A., Rojas-Valencia, N., Gómez, S., Cappelli, C., & Restrepo, A. (2021). The Role of Spike Protein Mutations in the Infectious Power of SARS-COV-2 Variants: A Molecular Interaction Perspective. Chembiochem : A European Journal of Chemical Biology. https://doi.org/10.1002/cbic.202100393Gorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., Penzar, D., Perlman, S., M Poon, L. L., Samborskiy, D. V, Sidorov, I. A., Sola, I., & Ziebuhr, J. (n.d.). The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology. https://doi.org/10.1038/s41564-020-0695-zGorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., Penzar, D., Perlman, S., Poon, L. L. M., Samborskiy, D. V., Sidorov, I. A., Sola, I., & Ziebuhr, J. (2020). The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology, 5(4), 536–544. https://doi.org/10.1038/S41564-020-0695-ZGorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leontovich, A. M., Neuman, B. W., Penzar, D., Perlman, S., Poon, L. L., Samborskiy, D., Sidorov, I. A., Sola, I., & Ziebuhr, J. (n.d.). Severe acute respiratory syndrome-related coronavirus: The species and its viruses-a statement of the Coronavirus Study Group. https://doi.org/10.1101/2020.02.07.937862Gordon, D. E., Jang, G. M., Bouhaddou, M., Xu, J., Obernier, K., White, K. M., O’Meara, M. J., Rezelj, V. V., Guo, J. Z., Swaney, D. L., Tummino, T. A., Hüttenhain, R., Kaake, R. M., Richards, A. L., Tutuncuoglu, B., Foussard, H., Batra, J., Haas, K., Modak, M., … Krogan, N. J. (2020). A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, 583(7816), 459–468. https://doi.org/10.1038/s41586-020-2286-9Greaney, A. J., Loes, A. N., Crawford, K. H. D., Starr, T. N., Malone, K. D., Chu, H. Y., & Bloom, J. D. (2021). Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host & Microbe, 29(3), 463. https://doi.org/10.1016/J.CHOM.2021.02.003Hadfield, J., Megill, C., Bell, S. M., Huddleston, J., Potter, B., Callender, C., Sagulenko, P., Bedford, T., & Neher, R. A. (2018). NextStrain: Real-time tracking of pathogen evolution. Bioinformatics, 34(23), 4121–4123. https://doi.org/10.1093/BIOINFORMATICS/BTY407Harrison, S. C. (2008). Viral membrane fusion. Nature Structural & Molecular Biology, 15(7), 690. https://doi.org/10.1038/NSMB.1456Hernández, M., García-Morán, E., Abad, D., & Eiros, J. M. (n.d.). GISAID: INICIATIVA INTERNACIONAL PARA COMPARTIR DATOS GENÓMICOS DEL VIRUS DE LA GRIPE Y DEL SARS-CoV-2. Retrieved December 3, 2023, from www.mscbs.es/respHeurich, A., Hofmann-Winkler, H., Gierer, S., Liepold, T., Jahn, O., & Pöhlmann, S. (2014). TMPRSS2 and ADAM17 Cleave ACE2 Differentially and Only Proteolysis by TMPRSS2 Augments Entry Driven by the Severe Acute Respiratory Syndrome Coronavirus Spike Protein. Journal of Virology, 88(2), 1293–1307. https://doi.org/10.1128/JVI.02202-13Hirotsu, Y., & Omata, M. (2021). Discovery of a SARS-CoV-2 variant from the P.1 lineage harboring K417T/E484K/N501Y mutations in Kofu, Japan. The Journal of Infection, 82(6), 276. https://doi.org/10.1016/J.JINF.2021.03.013Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052Holmes, E. C., Goldstein, S. A., Rasmussen, A. L., Robertson, D. L., Crits-Christoph, A., Wertheim, J. O., Anthony, S. J., Barclay, W. S., Boni, M. F., Doherty, P. C., Farrar, J., Geoghegan, J. L., Jiang, X., Leibowitz, J. L., Neil, S. J. D., Skern, T., Weiss, S. R., Worobey, M., Andersen, K. G., … Rambaut, A. (n.d.). Leading Edge The origins of SARS-CoV-2: A critical review. https://doi.org/10.1016/j.cell.2021.08.017Hu, B., Guo, H., Zhou, P., & Shi, Z.-L. (n.d.). Characteristics of SARS-CoV-2 and COVID-19. https://doi.org/10.1038/s41579-020-00459-7Hwang, S. S., Lim, J., Yu, Z., Kong, P., Sefik, E., Xu, H., Harman, C. C. D., Kim, L. K., Lee, G. R., Li, H. B., & Flavell, R. A. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, N.y.), 367(6483), 1260. https://doi.org/10.1126/SCIENCE.ABB2507Instituto Nacional de Salud. (n.d.). Coronavirus Colombia. Coronavirus Colombia. Retrieved January 26, 2024, from https://www.ins.gov.co/Noticias/Paginas/Coronavirus.aspxInstituto Nacional de Salud | Colombia Documentos tecnicos genomica. (n.d.). Retrieved January 23, 2024, from https://www.ins.gov.co/Paginas/Documentos-tecnicos-genomica.aspxKorber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E. E., Bhattacharya, T., Foley, B., Hastie, K. M., Parker, M. D., Partridge, D. G., Evans, C. M., Freeman, T. M., de Silva, T. I., Angyal, A., Brown, R. L., Carrilero, L., … Montefiori, D. C. (2020). Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell, 182(4), 812. https://doi.org/10.1016/J.CELL.2020.06.043Kuja, J. O., Kanoi, B. N., Balboa, R. F., Shiluli, C., Maina, M., Waweru, H., Gathii, K., Mungai, M., Masika, M., Anzala, O., Mwau, M., Clark, T. G., Waitumbi, J., & Gitaka, J. (2022). Genomic surveillance of SARS-COV-2 reveals diverse circulating variant lineages in Nairobi and Kiambu Counties, Kenya. BMC Genomics, 23(1). https://doi.org/10.1186/S12864-022-08853-6Laiton-Donato, K., Franco-Muñoz, C., Álvarez-Díaz, D. A., Ruiz-Moreno, H. A., Usme-Ciro, J. A., Prada, D. A., Reales-González, J., Corchuelo, S., Herrera-Sepúlveda, M. T., Naizaque, J., Santamaría, G., Rivera, J., Rojas, P., Ortiz, J. H., Cardona, A., Malo, D., Prieto-Alvarado, F., Gómez, F. R., Wiesner, M., … Mercado-Reyes, M. (2021). Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2. Infection, Genetics and Evolution, 95, 105038. https://doi.org/10.1016/J.MEEGID.2021.105038Laiton-Donato, K., Usme-Ciro, J. A., Franco-Muñoz, C., Álvarez-Díaz, D. A., Ruiz-Moreno, H. A., Reales-González, J., Prada, D. A., Corchuelo, S., Herrera-Sepúlveda, M. T., Naizaque, J., Santamaría, G., Wiesner, M., Walteros, D. M., Ospina Martínez, M. L., & Mercado-Reyes, M. (2021a). Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K. Frontiers in Medicine, 8, 697605. https://doi.org/10.3389/FMED.2021.697605/FULLLaiton-Donato, K., Usme-Ciro, J. A., Franco-Muñoz, C., Álvarez-Díaz, D. A., Ruiz-Moreno, H. A., Reales-González, J., Prada, D. A., Corchuelo, S., Herrera-Sepúlveda, M. T., Naizaque, J., Santamaría, G., Wiesner, M., Walteros, D. M., Ospina Martínez, M. L., & Mercado-Reyes, M. (2021b). Novel Highly Divergent SARS-CoV-2 Lineage With the Spike Substitutions L249S and E484K. Frontiers in Medicine, 8, 697605. https://doi.org/10.3389/FMED.2021.697605/FULLLan, J., Ge, J., Yu, J., Shan, S., Zhou, H., Fan, S., Zhang, Q., Shi, X., Wang, Q., Zhang, L., & Wang, X. (2020). Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature, 581(7807), 215–220. https://doi.org/10.1038/S41586-020-2180-5Li, Q., Guan, X., Wu, P., Wang, X., Zhou, L., Tong, Y., Ren, R., Leung, K. S. M., Lau, E. H. Y., Wong, J. Y., Xing, X., Xiang, N., Wu, Y., Li, C., Chen, Q., Li, D., Liu, T., Zhao, J., Liu, M., … Feng, Z. (2020). Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia. The New England Journal of Medicine, 382(13), 1199. https://doi.org/10.1056/NEJMOA2001316Lieb, W., Graf, J., Götz, A., König, I. R., Mayer, B., Fischer, M., Stritzke, J., Hengstenberg, C., Holmer, S. R., Döring, A., Löwel, H., Schunkert, H., & Erdmann, J. (2006). Association of angiotensin-converting enzyme 2 (ACE2) gene polymorphisms with parameters of left ventricular hypertrophy in men. Results of the MONICA Augsburg echocardiographic substudy. Journal of Molecular Medicine (Berlin, Germany), 84(1), 88–96. https://doi.org/10.1007/S00109-005-0718-5Lorenzo-Redondo, R., Nam, H. H., Roberts, S. C., Simons, L. M., Jennings, L. J., Qi, C., Achenbach, C. J., Hauser, A. R., Ison, M. G., Hultquist, J. F., & Ozer, E. A. (n.d.). A Unique Clade of SARS-CoV-2 Viruses is Associated with Lower Viral Loads in Patient Upper Airways. https://doi.org/10.1101/2020.05.19.20107144Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., … Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Www.Thelancet.Com, 395, 565. https://doi.org/10.1016/S0140-6736(20)30251-8Martínez-Gómez, L. E., Herrera-López, B., Martinez-Armenta, C., Ortega-Peña, S., Camacho-Rea, M. del C., Suarez-Ahedo, C., Vázquez-Cárdenas, P., Vargas-Alarcón, G., Rojas-Velasco, G., Fragoso, J. M., Vidal-Vázquez, P., Ramírez-Hinojosa, J. P., Rodríguez-Sánchez, Y., Barrón-Díaz, D., Moreno, M. L., Martínez-Ruiz, F. de J., Zayago-Angeles, D. M., Mata-Miranda, M. M., Vázquez-Zapién, G. J., López-Reyes, A. (2022). ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men. Frontiers in Immunology, 13, 1. https://doi.org/10.3389/FIMMU.2022.812940/FULLMedina-Enríquez, M. M., Lopez-León, S., Carlos-Escalante, J. A., Aponte-Torres, Z., Cuapio, A., & Wegman-Ostrosky, T. (2020). ACE2: the molecular doorway to SARS-CoV-2. In Cell and Bioscience (Vol. 10, Issue 1). BioMed Central Ltd. https://doi.org/10.1186/s13578-020-00519-8Menachery, V. D., Yount, B. L., Debbink, K., Agnihothram, S., Gralinski, L. E., Plante, J. A., Graham, R. L., Scobey, T., Ge, X. Y., Donaldson, E. F., Randell, S. H., Lanzavecchia, A., Marasco, W. A., Shi, Z. L., & Baric, R. S. (2015). A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Nature Medicine, 21(12), 1508–1513. https://doi.org/10.1038/nm.3985Mio, C., Secco, C. D., Marzinotto, S., Pipan, C., Sozio, E., Tascini, C., Damante, G., & Curcio, F. (2022). Correspondence: Monitoring the SPREAD of the SARS-CoV-2 lineage B.1.621 in Udine, Italy. Journal of Clinical Pathology, 75(10), 712. https://doi.org/10.1136/JCLINPATH-2021-207810Nextclade. (n.d.). Retrieved January 6, 2024, from https://clades.nextstrain.org/Nieto-Torres, J. L., DeDiego, M. L., Verdiá-Báguena, C., Jimenez-Guardeño, J. M., Regla-Nava, J. A., Fernandez-Delgado, R., Castaño-Rodriguez, C., Alcaraz, A., Torres, J., Aguilella, V. M., & Enjuanes, L. (2014). Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis. PLoS Pathogens, 10(5). https://doi.org/10.1371/journal.ppat.1004077Örd, M., Faustova, I., & Loog, M. (2020). The sequence at Spike S1/S2 site enables cleavage by furin and phospho-regulation in SARS-CoV2 but not in SARS-CoV1 or MERS-CoV. Scientific Reports 2020 10:1, 10(1), 1–10. https://doi.org/10.1038/s41598-020-74101-0Organizaciòn mundial de la salud. (n.d.). Panel de control de la OMS sobre el coronavirus (COVID-19).Organization, W. H. (2021). WHO-convened global study of origins of SARS-CoV-2: China part.Park, S. T., & Kim, J. (2016). Trends in Next-Generation Sequencing and a New Era for Whole Genome Sequencing. International Neurourology Journal, 20(Suppl 2), S76. https://doi.org/10.5213/INJ.1632742.371Pekar, J. E., Magee, A., Parker, E., Moshiri, N., Izhikevich, K., Havens, J. L., Gangavarapu, K., Mariana, L., Serrano, M., Crits-Christoph, A., Matteson, N. L., Zeller, M., Levy, J. I., Wang, J. C., Hughes, S., Lee, J., Ching, K., Yan, Z., Tzer, R., … Wertheim, J. O. (n.d.). The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2. https://www.science.orgPrimer3. (n.d.). Retrieved January 5, 2024, from https://primer3.org/Propuestas aprobadas | ICTV. (n.d.). Retrieved December 8, 2023, from https://ictv.global/files/proposals/approved?fid=4929Quintana-Murci, L. (2016). Genetic and epigenetic variation of human populations: An adaptive tale. Comptes Rendus Biologies, 339(7–8), 278–283. https://doi.org/10.1016/J.CRVI.2016.04.005Rambaut, A., Holmes, E. C., OToole, Á., Hill, V., McCrone, J. T., Ruis, C., du Plessis, L., & Pybus, O. G. (n.d.). A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nature Microbiology. https://doi.org/10.1038/s41564-020-0770-5Ravi, V., Saxena, S., & Panda, P. S. (2022). Basic virology of SARS-CoV 2. Indian Journal of Medical Microbiology, 40(2), 182. https://doi.org/10.1016/J.IJMMB.2022.02.005Rivero, R., Garay, E., Botero, Y., Serrano-Coll, H., Gastelbondo, B., Muñoz, M., Ballesteros, N., Castañeda, S., Patiño, L. H., Ramirez, J. D., Calderon, A., Guzmán, C., Martinez-Bravo, C., Aleman, A., Arrieta, G., & Mattar, S. (2022). Human-to-dog transmission of SARS-CoV-2, Colombia. Scientific Reports, 12(1). https://doi.org/10.1038/S41598-022-11847-9Sabater Molina, M., Nicolás Rocamora, E., Bendicho, A. I., Vázquez, E. G., Zorio, E., Rodriguez, F. D., Gil Ortuño, C., Rodríguez, A. I., Sánchez-López, A. J., Jara Rubio, R., Moreno-Docón, A., Marcos, P. J., García Pavía, P., Villa, R. B., & Gimeno Blanes, J. R. (2022). Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease. PloS One, 17(2), e0263140. https://doi.org/10.1371/JOURNAL.PONE.0263140Sahajpal, V., Rajput, S., Sharma, T., Sharma, A., & Thakar, M. K. (2019). Development and evaluation of a novel DNA purification buffer and protocol for blood samples on FTA cards. Forensic Science International: Reports, 1, 100014. https://doi.org/10.1016/J.FSIR.2019.100014Secuenciación genómica y caracterización genética del virus de la influenza | CDC. (n.d.). Retrieved January 27, 2024, from https://espanol.cdc.gov/flu/about/professionals/genetic-characterization.htmSecuenciacion-genoma-completo-SARS-COV-2-secuenciador-MINION. (n.d.).Senapati, S., Banerjee, P., Bhagavatula, S., Kushwaha, P. P., & Kumar, S. (2021). Contributions of human ACE2 and TMPRSS2 in determining host–pathogen interaction of COVID-19. In Journal of Genetics (Vol. 100, Issue 1). Springer. https://doi.org/10.1007/s12041-021-01262-wShang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020a). Structural basis of receptor recognition by SARS-CoV-2. Nature 2020 581:7807, 581(7807), 221–224. https://doi.org/10.1038/s41586-020-2179-yShang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020b). Structural basis of receptor recognition by SARS-CoV-2. Nature, 581(7807), 221. https://doi.org/10.1038/S41586-020-2179-YShovlin, C. L., & Vizcaychipi, M. P. (2020). COVID-19 genomic susceptibility: Definition of ACE2 variants relevant to human infection with SARS-CoV-2 in the context of ACMG/AMP Guidance. MedRxiv, 2020.05.12.20098160. https://doi.org/10.1101/2020.05.12.20098160Siddell, S. G., Walker, P. J., Lefkowitz, E. J., Mushegian, A. R., Adams, M. J., Dutilh, B. E., Gorbalenya, A. E., Harrach, B., Harrison, R. L., Junglen, S., Knowles, N. J., Kropinski, A. M., Krupovic, M., Kuhn, J. H., Nibert, M., Rubino, L., Sabanadzovic, S., Sanfaçon, H., Simmonds, P., … Davison, A. J. (2019). Additional changes to taxonomy ratified in a special vote by the International Committee on Taxonomy of Viruses (October 2018). Archives of Virology, 164(3), 943–946. https://doi.org/10.1007/S00705-018-04136-2Simmons, G., Gosalia, D. N., Rennekamp, A. J., Reeves, J. D., Diamond, S. L., & Bates, P. (2005). Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proceedings of the National Academy of Sciences of the United States of America, 102(33), 11876. https://doi.org/10.1073/PNAS.0505577102Simmons, G., Zmora, P., Gierer, S., Heurich, A., & Pöhlmann, S. (2013). Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research. Antiviral Research, 100(3), 605. https://doi.org/10.1016/J.ANTIVIRAL.2013.09.028Singh, D., & Yi, S. V. (2021). On the origin and evolution of SARS-CoV-2. Experimental & Molecular Medicine, 53, 537–547. https://doi.org/10.1038/s12276-021-00604-zSituación del SARS CoV2 - Región de las Américas - OPS/OMS | Organización Panamericana de la Salud. (n.d.). Retrieved January 13, 2024, from https://www.paho.org/en/covid-19-weekly-updates-region-americasSun, P., Lu, X., Xu, C., Sun, W., & Pan, B. (2020). Understanding of COVID-19 based on current evidence. Journal of Medical Virology, 92(6), 548–551. https://doi.org/10.1002/JMV.25722Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., Mlisana, K., von Gottberg, A., Walaza, S., Allam, M., Ismail, A., Mohale, T., Glass, A. J., Engelbrecht, S., Van Zyl, G., … de Oliveira, T. (2021). Detection of a SARS-CoV-2 variant of concern in South Africa. Nature, 592(7854), 438–443. https://doi.org/10.1038/S41586-021-03402-9The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. (2020). European Journal of Human Genetics, 28(6), 715–718. https://doi.org/10.1038/s41431-020-0636-6Thomas, S. (2021). Mapping the Nonstructural Transmembrane Proteins of Severe Acute Respiratory Syndrome Coronavirus 2. Journal of Computational Biology, 28(9), 909–921. https://doi.org/10.1089/cmb.2020.0627Torre-Fuentes, L., Matías-Guiu, J., Hernández-Lorenzo, L., Montero-Escribano, P., Pytel, V., Porta-Etessam, J., Gómez-Pinedo, U., & Matías-Guiu, J. A. (2021). ACE2, TMPRSS2, and Furin variants and SARS-CoV-2 infection in Madrid, Spain. Journal of Medical Virology, 93(2), 863–869. https://doi.org/10.1002/jmv.26319Tortorici, M. A., & Veesler, D. (2019). Structural insights into coronavirus entry. In Advances in Virus Research (Vol. 105, pp. 93–116). Academic Press Inc. https://doi.org/10.1016/bs.aivir.2019.08.002(US), N. I. of H., & Study, B. S. C. (2007). Understanding Human Genetic Variation. https://www.ncbi.nlm.nih.gov/books/NBK20363/Vadgama, N., Kreymerman, A., Campbell, J., Shamardina, O., Brugger, C., Research Consortium, G. E., Deaconescu, A. M., Lee, R. T., Penkett, C. J., Gifford, C. A., Mercola, M., Nasir, J., & Karakikes, I. (2022). SARS-CoV-2 Susceptibility and ACE2 Gene Variations Within Diverse Ethnic Backgrounds. Frontiers in Genetics, 13, 888025. https://doi.org/10.3389/FGENE.2022.888025/BIBTEXVolz, E., Mishra, S., Chand, M., Barrett, J. C., Johnson, R., Geidelberg, L., Hinsley, W. R., Laydon, D. J., Dabrera, G., O’Toole, Á., Amato, R., Ragonnet-Cronin, M., Harrison, I., Jackson, B., Ariani, C. V., Boyd, O., Loman, N. J., McCrone, J. T., Gonçalves, S., … Ferguson, N. M. (2021). Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature, 593(7858), 266–269. https://doi.org/10.1038/S41586-021-03470-XWalls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020). Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell, 181(2), 281. https://doi.org/10.1016/J.CELL.2020.02.058Wang, N., Li, S. Y., Yang, X. Lou, Huang, H. M., Zhang, Y. J., Guo, H., Luo, C. M., Miller, M., Zhu, G., Chmura, A. A., Hagan, E., Zhou, J. H., Zhang, Y. Z., Wang, L. F., Daszak, P., & Shi, Z. L. (2018). Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China. Virologica Sinica, 33(1), 104. https://doi.org/10.1007/S12250-018-0012-7WHO COVID-19 weekly epidemiological update vol. 74... - Google Académico. (n.d.). Retrieved January 2, 2024, from https://scholar.google.com/scholar?q=WHO+COVID-19+weekly+epidemiological+update+vol.+74+January+2022+World+Health+organization+Wolf, J. M., Wolf, L. M., Bello, G. L., Maccari, J. G., & Nasi, L. A. (2023). Molecular evolution of SARS‐CoV‐2 from December 2019 to August 2022. Journal of Medical Virology, 95(1). https://doi.org/10.1002/JMV.28366Wong, S. K., Li, W., Moore, M. J., Choe, H., & Farzan, M. (2004). A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2. Journal of Biological Chemistry, 279(5), 3197–3201. https://doi.org/10.1074/jbc.C300520200Wu, C. rong, Yin, W. chao, Jiang, Y., & Xu, H. E. (2022). Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19. In Acta Pharmacologica Sinica (Vol. 43, Issue 12, pp. 3021–3033). Springer Nature. https://doi.org/10.1038/s41401-021-00851-wWu, F., Zhao, S., Yu, B., Chen, Y.-M., Wang, W., Song, Z.-G., Hu, Y., Tao, Z.-W., Tian, J.-H., Pei, Y.-Y., Yuan, M.-L., Zhang, Y.-L., Dai, F.-H., Liu, Y., Wang, Q.-M., Zheng, J.-J., Xu, L., Holmes, E. C., & Zhang, Y.-Z. (2008). A new coronavirus associated with human respiratory disease in China. Nature, 579. https://doi.org/10.1038/s41586-020-2008-3Xiao, X., Newman, C., Buesching, C. D., Macdonald, D. W., & Zhou, Z.-M. (123 C.E.). Animal sales from Wuhan wet markets immediately prior to the COVID-19 pandemic. Scientific Reports |, 11, 11898. https://doi.org/10.1038/s41598-021-91470-2Xie, X., Liu, Y., Liu, J., Zhang, X., Zou, J., Fontes-Garfias, C. R., Xia, H., Swanson, K. A., Cutler, M., Cooper, D., Menachery, V. D., Weaver, S. C., Dormitzer, P. R., & Shi, P. Y. (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature Medicine, 27(4), 620–621. https://doi.org/10.1038/S41591-021-01270-4Yadav, R., Chaudhary, J. K., Jain, N., Chaudhary, P. K., Khanra, S., Dhamija, P., Sharma, A., Kumar, A., & Handu, S. (2021). cells Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19. 10, 821. https://doi.org/10.3390/cellsYan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y., & Zhou, Q. (2020). Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. In Science (Vol. 367).Yang, J., Petitjean, S. J. L., Koehler, M., Zhang, Q., Dumitru, A. C., Chen, W., Derclaye, S., Vincent, S. P., Soumillion, P., & Alsteens, D. (2020). Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-18319-6Yoshimoto, F. K. (1234). The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2 or n-COV19), the Cause of COVID-19. The Protein Journal, 39, 198–216. https://doi.org/10.1007/s10930-020-09901-4Zeberg, H., & Pääbo, S. (2020). The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature 2020 587:7835, 587(7835), 610–612. https://doi.org/10.1038/s41586-020-2818-3Zhu, L., Marsh, J. W., Griffith, M. P., Collins, K., Srinivasa, V., Waggle, K., Van Tyne, D., Snyder, G. M., Phan, T., Wells, A., Marroquin, O. C., & Harrison, L. H. (2022). Predictive model for severe COVID-19 using SARS-CoV-2 whole-genome sequencing and electronic health record data, March 2020-May 2021. PLoS ONE, 17(7). https://doi.org/10.1371/JOURNAL.PONE.0271381Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., Zhao, X., Huang, B., Shi, W., Lu, R., Niu, P., Zhan, F., Ma, X., Wang, D., Xu, W., Wu, G., Gao, G. F., Tan, W., & China Novel Coronavirus Investigating and Research Team. (2020). A Novel Coronavirus from Patients with Pneumonia in China, 2019. The New England Journal of Medicine, 382(8), 727–733. https://doi.org/10.1056/NEJMoa2001017Glowacka, I., Bertram, S., Müller, M. A., Allen, P., Soilleux, E., Pfefferle, S., Steffen, I., Tsegaye, T. S., He, Y., Gnirss, K., Niemeyer, D., Schneider, H., Drosten, C., & Pöhlmann, S. (2011b). Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response. Journal of Virology, 85(9), 4122–4134. https://doi.org/10.1128/JVI.02232-10BibliotecariosEstudiantesInvestigadoresPersonal de apoyo escolarPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/86453/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL1030666404.2024.pdf1030666404.2024.pdfapplication/pdf1416032https://repositorio.unal.edu.co/bitstream/unal/86453/2/1030666404.2024.pdf194bcde4506763c6ad73fd6f45efd53dMD52THUMBNAIL1030666404.2024.pdf.jpg1030666404.2024.pdf.jpgGenerated Thumbnailimage/jpeg5594https://repositorio.unal.edu.co/bitstream/unal/86453/3/1030666404.2024.pdf.jpg4df2a62f88cd2b5ade038a7f5a3f48a6MD53unal/86453oai:repositorio.unal.edu.co:unal/864532024-07-16 23:05:09.03Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.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