Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana
ilustraciones, diagramas
- Autores:
-
Gómez Muñoz, Laura Alejandra
- Tipo de recurso:
- Fecha de publicación:
- 2022
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/84652
- Palabra clave:
- 570 - Biología::572 - Bioquímica
610 - Medicina y salud::616 - Enfermedades
540 - Química y ciencias afines::543 - Química analítica
COVID-19
SARS-CoV-2
Metabolomics
Lipidomics
Prognostic factors
Metabolómica
Lipidómica
Factores pronósticos
- Rights
- openAccess
- License
- Atribución-NoComercial-SinDerivadas 4.0 Internacional
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oai:repositorio.unal.edu.co:unal/84652 |
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UNACIONAL2 |
network_name_str |
Universidad Nacional de Colombia |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana |
dc.title.translated.eng.fl_str_mv |
Evaluation of the metabolomic profile and its relationship with the clinical spectrum of positive subjects for SARS-COV-2 in a Bogota population |
title |
Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana |
spellingShingle |
Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana 570 - Biología::572 - Bioquímica 610 - Medicina y salud::616 - Enfermedades 540 - Química y ciencias afines::543 - Química analítica COVID-19 SARS-CoV-2 Metabolomics Lipidomics Prognostic factors Metabolómica Lipidómica Factores pronósticos |
title_short |
Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana |
title_full |
Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana |
title_fullStr |
Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana |
title_full_unstemmed |
Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana |
title_sort |
Evaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotana |
dc.creator.fl_str_mv |
Gómez Muñoz, Laura Alejandra |
dc.contributor.advisor.none.fl_str_mv |
Sandoval Hernández, Adrián Gabriel Cala Molina, Monica Patricia |
dc.contributor.author.none.fl_str_mv |
Gómez Muñoz, Laura Alejandra |
dc.contributor.educationalvalidator.none.fl_str_mv |
Arboleda Granados Humberto Santamaria Torres Mary Andrea |
dc.contributor.graphicaldesigner.none.fl_str_mv |
Gómez Muñoz Lilia Nataly |
dc.contributor.researchgroup.spa.fl_str_mv |
Muerte Celular |
dc.contributor.cvlac.spa.fl_str_mv |
Gómez-Muñoz, L. A |
dc.subject.ddc.spa.fl_str_mv |
570 - Biología::572 - Bioquímica 610 - Medicina y salud::616 - Enfermedades 540 - Química y ciencias afines::543 - Química analítica |
topic |
570 - Biología::572 - Bioquímica 610 - Medicina y salud::616 - Enfermedades 540 - Química y ciencias afines::543 - Química analítica COVID-19 SARS-CoV-2 Metabolomics Lipidomics Prognostic factors Metabolómica Lipidómica Factores pronósticos |
dc.subject.proposal.eng.fl_str_mv |
COVID-19 SARS-CoV-2 Metabolomics Lipidomics Prognostic factors |
dc.subject.proposal.spa.fl_str_mv |
Metabolómica Lipidómica Factores pronósticos |
description |
ilustraciones, diagramas |
publishDate |
2022 |
dc.date.issued.none.fl_str_mv |
2022-12-20 |
dc.date.accessioned.none.fl_str_mv |
2023-09-05T20:11:57Z |
dc.date.available.none.fl_str_mv |
2023-09-05T20:11:57Z |
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/84652 |
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/84652 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 |
Alsharif W, Qurashi A. Effectiveness of COVID-19 diagnosis and management tools: A review. Radiogr (London, Engl 1995). 2021 May 1;27(2):682. Available from: /pmc/articles/PMC7505601/ COVID Live Update: Cases and Deaths from the Coronavirus - Worldometer. Available from: https://www.worldometers.info/coronavirus/?utm_campaign=homeAdvegas1? El Coronavirus en Colombia. Available from: https://coronaviruscolombia.gov.co/Covid19/index.html OMS O mundial de la salud. Nuevo coronavirus 2019. Available from: https://www.who.int/es/emergencies/diseases/novel-coronavirus-2019?gclid=EAIaIQobChMI_8TIx6iE9AIViYKGCh0H1ADqEAAYASAAEgLfDPD_BwE Jiang S, Hillyer C, Du L. Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses. Trends Immunol2020 May 1;41(5):355. Available from: /pmc/articles/PMC7129017/ Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England). 2020 Feb 15;395(10223):497. Available from: /pmc/articles/PMC7159299/ Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat Nanotechnol. 2020 Apr 1;15(4):1. Available from: /pmc/articles/PMC7094976/ OMS. La OMS interrumpe los grupos de tratamiento de la COVID-19 con hidroxicloroquina y con la combinación lopinavir/ritonavir. Available from: https://www.who.int/es/news/item/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19 Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis. 2021 Jan 1;21(1):39. Available from: /pmc/articles/PMC7561304/ Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov. 2020 May 1;19(5):305–6. Ura T, Yamashita A, Mizuki N, Okuda K, Shimada M. New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates. Vaccine. 2021 Jan 8;39(2):197. Available from: /pmc/articles/PMC7685034/ Chakraborty S, Mallajosyula V, Tato CM, Tan GS, Wang TT. SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand? Adv Drug Deliv Rev. 2021 May 1;172:314. Available from: /pmc/articles/PMC7816567/ OMS. Enfermedad por el coronavirus (COVID-19): Vacunas. Available from: https://www.who.int/es/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-(covid-19)-vaccines?adgroupsurvey=%7Badgroupsurvey%7D&gclid=Cj0KCQiAi9mPBhCJARIsAHchl1xgy5gL27gOo_lHlJ7Je7rmbUnhm8OQcOJwqZrFxb2yXkrV OMS. Lo que debe saber sobre la vacuna de Pfizer-BioNTech (BNT162b2) contra la COVID-19. Available from: https://www.who.int/es/news-room/feature-stories/detail/who-can-take-the-pfizer-biontech-covid-19--vaccine-what-you-need-to-know Awadasseid A, Wu Y, Tanaka Y, Zhang W. Current advances in the development of SARS-CoV-2 vaccines. Int J Biol Sci. 2021;17(1):8. Available from: /pmc/articles/PMC7757035/ Baig AM. Computing the Effects of SARS-CoV-2 on RespirationRegulatory Mechanisms in COVID-19. ACS Chem Neurosci. 2020 Aug 19;11(16):2416. Available from: /pmc/articles/PMC7422910/ Irabien-Ortiz Á, Carreras-Mora J, Sionis A, Pàmies J, Montiel J, Tauron M. Fulminant myocarditis due to COVID-19. Rev Española Cardiol (English Ed. 2020 Jun 1;73(6):503–4. Available from: http://www.revespcardiol.org/en-fulminant-myocarditis-due-covid-19-articulo-S1885585720301651 Garot J, Amour J, Pezel T, Dermoch F, Messadaa K, Felten M-L, et al. SARS-CoV-2 Fulminant Myocarditis. JACC Case Reports. 2020 Jul;2(9):1342. Available from: /pmc/articles/PMC7274592/ Gauchotte G, Venard V, Segondy M, Cadoz C, Esposito-Fava A, Barraud D, et al. SARS-Cov-2 fulminant myocarditis: an autopsy and histopathological case study. Int J Legal Med. 2021 Mar 1;135(2):1. Available from: /pmc/articles/PMC7779100/ Schrimpe-Rutledge AC, Codreanu SG, Sherrod SD, McLean JA. Untargeted metabolomics strategies – Challenges and Emerging Directions. J Am Soc Mass Spectrom. 2016 Dec 1;27(12):1897. Available from: /pmc/articles/PMC5110944/ Jang C, Chen L, Rabinowitz JD. Metabolomics and isotope tracing. Cell. 2018 May 3;173(4):822. Available from: /pmc/articles/PMC6034115/ Sreepadmanabh M, Sahu AK, Chande A. COVID-19: Advances in diagnostic tools, treatment strategies, and vaccine development. J Biosci. 2020 Dec 1;45(1). Available from: /pmc/articles/PMC7683586/ V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 2020 193. 2020 Oct 28;19(3):155–70. Available from: https://www.nature.com/articles/s41579-020-00468-6 Naqvi AAT, Fatima K, Mohammad T, Fatima U, Singh IK, Singh A, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165878. Available from: /pmc/articles/PMC7293463/ B Hu, H Guo, P Zhou, ZL Shi. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021 Mar 1;19(3):141–54. Available from: https://pubmed.ncbi.nlm.nih.gov/33024307/ Chung JY, Thone MN, Kwon YJ. COVID-19 vaccines: The status and perspectives in delivery points of view. Adv Drug Deliv Rev. 2021 Mar 1;170:1. Available from: /pmc/articles/PMC7759095/ Ahn D-G, Shin H-J, Kim M-H, Lee S, Kim H-S, Myoung J, et al. Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19). J Microbiol Biotechnol. 2020 Mar 28;30(3):313–24. Available from: https://www.jmb.or.kr/journal/view.html?doi=10.4014/jmb.2003.03011 Gao Z, Xu Y, Sun C, Wang X, Guo Y, Qiu S, et al. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect. 2021 Feb 1;54(1):12. Available from: /pmc/articles/PMC7227597/ Organization PAH. Epidemiological Update: Coronavirus disease (COVID-19). Pan Am Heal Organ. 2021 Aug 21; Available from: https://iris.paho.org/handle/10665.2/54717 Atzrodt CL, Maknojia I, McCarthy RDP, Oldfield TM, Po J, Ta KTL, et al. A Guide to COVID‐19: a global pandemic caused by the novel coronavirus SARS‐CoV‐2. Febs J. 2020 Sep 1;287(17):3633–50. Available from: /pmc/articles/PMC7283703/?report=abstract OMS. Seguimiento de las variantes del SARS-CoV-2. 2021. Available from: https://www.who.int/es/activities/tracking-SARS-CoV-2-variants/tracking-SARS-CoV-2-variants Yan W, Zheng Y, Zeng X, He B, Cheng W. Structural biology of SARS-CoV-2: open the door for novel therapies. Signal Transduct Target Ther 2022 71. 2022 Jan 27;7(1):1–28. Available from: https://www.nature.com/articles/s41392-022-00884-5 Instituto Nacional de salud de C. Noticias coronavirus-casos. 2021. Available from: https://www.ins.gov.co/Noticias/Paginas/coronavirus-casos.aspx Instituto Nacional de salud de C. COVID-19 en Colombia, Reporte diario. 2022. Available from: https://www.ins.gov.co/Noticias/paginas/coronavirus.aspx Organización Panamericana de la Salud (OPS). REPORTE: Situación COVID-19 Colombia. 2022. Fehr AR, Perlman S. Coronaviruses: An Overview of Their Replication and Pathogenesis. Coronaviruses. 2015 Feb 26;1282:1. Available from: /pmc/articles/PMC4369385/ Wang F, Kream RM, Stefano GB. An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development. Med Sci Monit. 2020;26:e924700-1. Available from: /pmc/articles/PMC7218962/ Hardenbrook NJ, Zhang P. A structural view of the SARS-CoV-2 virus and its assembly. Curr Opin Virol. 2022 Feb 1;52:123–34. Ke Z, Oton J, Qu K, Cortese M, Zila V, McKeane L, et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nat 2020 5887838. 2020 Aug 17;588(7838):498–502. Available from: https://www.nature.com/articles/s41586-020-2665-2 Alfonso Accinelli R, Zhang Xu CM, Ju Wang J-D, Yachachin-Chávez JM, Cáceres-Pizarro JA, Tafur-Bances KB, et al. COVID-19: LA PANDEMIA POR EL NUEVO VIRUS SARS-CoV-2. Rev Peru Med Exp Salud Publica. 2020 Apr 20;37(2):302–11. Available from: https://www.scielosp.org/pdf/rpmesp/2020.v37n2/302-311/es Kirtipal N, Bharadwaj S, Kang SG. From SARS to SARS-CoV-2, insights on structure, pathogenicity and immunity aspects of pandemic human coronaviruses. Infect Genet Evol. 2020 Nov 1;85:104502. Available from: /pmc/articles/PMC7425554/ Benavides-Rosero MF, Benavides-Rosero MF. COVID-19 y la pandemia global causada por un nuevo coronavirus. Univ y Salud. 2020 Dec 10;22(3):299–314. Available from: http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0124-71072020000400299&lng=en&nrm=iso&tlng=es Harrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 Transmission and Pathogenesis. Trends Immunol. 2020 Dec 1;41(12):1100. Available from: /pmc/articles/PMC7556779/ Arya R, Kumari S, Pandey B, Mistry H, Bihani SC, Das A, et al. Structural insights into SARS-CoV-2 proteins. J Mol Biol. 2021 Jan 22;433(2):166725. Available from: /pmc/articles/PMC7685130/ Giovanetti M, Benedetti F, Campisi G, Ciccozzi A, Fabris S, Ceccarelli G, et al. Evolution patterns of SARS-CoV-2: Snapshot on its genome variants. Biochem Biophys Res Commun. 2021 Jan 29;538:88. Available from: /pmc/articles/PMC7836704/ Flower TG, Buffalo CZ, Hooy RM, Allaire M, Ren X, Hurley JH. Structure of SARS-cov-2 ORF8, a rapidly evolving immune evasion protein. Proc Natl Acad Sci U S A. 2021 Jan 12;118(2). Available from: /pmc/articles/PMC7812859/ Huang Y, Yang C, Xu X feng, Xu W, Liu S wen. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020 419. 2020 Aug 3;41(9):1141–9. Available from: https://www.nature.com/articles/s41401-020-0485-4 Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 2021 231. 2021 Oct 5;23(1):3–20. Available from: https://www.nature.com/articles/s41580-021-00418-x Groves DC, Rowland-Jones SL, Angyal A. The D614G mutations in the SARS-CoV-2 spike protein: Implications for viral infectivity, disease severity and vaccine design. Biochem Biophys Res Commun. 2021 Jan 29;538:104. Available from: /pmc/articles/PMC7643658/ Zhang J, Cai Y, Xiao T, Lu J, Peng H, Sterling SM, et al. Structural impact on SARS-CoV-2 spike protein by D614G substitution. Science. 2021 Apr 30;372(6541):525. Available from: /pmc/articles/PMC8139424/ Wang MY, Zhao R, Gao LJ, Gao XF, Wang DP, Cao JM. SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development. Front Cell Infect Microbiol. 2020 Nov 25;10. Available from: /pmc/articles/PMC7723891/ Zhou P, Yang X Lou, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar 12;579(7798):270. Available from: /pmc/articles/PMC7095418/ Scialo F, Daniele A, Amato F, Pastore L, Matera MG, Cazzola M, et al. ACE2: The Major Cell Entry Receptor for SARS-CoV-2. Lung. 2020 Dec 1;198(6):867. Available from: /pmc/articles/PMC7653219/ Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 May 28;581(7809):465–9. Available from: https://pubmed.ncbi.nlm.nih.gov/32235945/ Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020 May 28;181(5):1016. Available from: /pmc/articles/PMC7252096/ Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020 Dec 1;12(1). Available from: /pmc/articles/PMC7039956/ Suryamohan K, Diwanji D, Stawiski EW, Gupta R, Miersch S, Liu J, et al. Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2. Commun Biol 2021 41. 2021 Apr 12;4(1):1–11. Available from: https://www.nature.com/articles/s42003-021-02030-3 Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet (London, England). 2020 Feb 22;395(10224):565. Available from: /pmc/articles/PMC7159086/ Mariano G, Farthing RJ, Lale-Farjat SLM, Bergeron JRC. Structural Characterization of SARS-CoV-2: Where We Are, and Where We Need to Be. Front Mol Biosci. 2020 Dec 17;7:344. Li C, Lee A, Grigoryan L, Arunachalam PS, Scott MKD, Trisal M, et al. Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine. Nat Immunol. 2022 Apr 1;23(4):543. Available from: /pmc/articles/PMC8989677/ Tian JH, Patel N, Haupt R, Zhou H, Weston S, Hammond H, et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021 Dec 1;12(1). Available from: /pmc/articles/PMC7809486/ Xia X. Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design. Viruses. 2021 Jan 1;13(1). Available from: /pmc/articles/PMC7829931/ Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603–15. Available from: /pmc/articles/PMC7745181/ Kang YF, Sun C, Zhuang Z, Yuan RY, Zheng Q, Li JP, et al. Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates. ACS Nano. 2021 Feb 23;15(2):2738–52. Available from: /pmc/articles/PMC7839421/ Yadav R, Chaudhary JK, Jain N, Chaudhary PK, Khanra S, Dhamija P, et al. Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19. Cells. 2021 Apr 1;10(4). Available from: /pmc/articles/PMC8067447/ Lu S, Ye Q, Singh D, Cao Y, Diedrich JK, Yates JR, et al. The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nat Commun. 2021 Dec 1;12(1). Available from: /pmc/articles/PMC7820290/ Wang W, Chen J, Yu X, Lan HY. Signaling mechanisms of SARS-CoV-2 Nucleocapsid protein in viral infection, cell death and inflammation. Int J Biol Sci. 2022;18(12):4704. Available from: /pmc/articles/PMC9305276/ Karjee S, Mukherjee SK. RNAi suppressor: The hidden weapon of SARS-CoV. J Biosci. 2020 Dec 1;45(1). Available from: /pmc/articles/PMC7363689/ Kadam SB, Sukhramani GS, Bishnoi P, Pable AA, Barvkar VT. SARS‐CoV‐2, the pandemic coronavirus: Molecular and structural insights. J Basic Microbiol. 2021 Mar 1;61(3):180. Available from: /pmc/articles/PMC8013332/ Cao Y, Yang R, Lee I, Zhang W, Sun J, Wang W, et al. Characterization of the SARS‐CoV‐2 E Protein: Sequence, Structure, Viroporin, and Inhibitors. Protein Sci. 2021 Jun 1;30(6):1114. Available from: /pmc/articles/PMC8138525/ Noori R, Sardar M. An outlook on potential protein targets of COVID-19 as a druggable site. Mol Biol Rep [Internet]. 2022 Nov 1;49(11):10729–48. Available from: https://link.springer.com/article/10.1007/s11033-022-07724-3 Zhang Z, Nomura N, Muramoto Y, Ekimoto T, Uemura T, Liu K, et al. Structure of SARS-CoV-2 membrane protein essential for virus assembly. Nat Commun 2022 131. 2022 Aug 5;13(1):1–12. Available from: https://www.nature.com/articles/s41467-022-32019-3 Shen L, Bard JD, Triche TJ, Judkins AR, Biegel JA, Gai X. Emerging variants of concern in SARS-CoV-2 membrane protein: a highly conserved target with potential pathological and therapeutic implications. Emerg Microbes Infect. 2021;10(1):885. Available from: /pmc/articles/PMC8118436/ Hu Y, Wen J, Tang L, Zhang H, Zhang X, Li Y, et al. The M Protein of SARS-CoV: Basic Structural and Immunological Properties. Genomics Proteomics Bioinformatics. 2003;1(2):118. Available from: /pmc/articles/PMC5172243/ Sui L, Zhao Y, Wang W, Wu P, Wang Z, Yu Y, et al. SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1. Front Immunol. 2021 May 18;12. Available from: /pmc/articles/PMC8168463/ Thomas S. The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET. Pathog Immun [Internet]. 2020;5(1):342. Available from: /pmc/articles/PMC7608487/ Pizzato M, Baraldi C, Boscato Sopetto G, Finozzi D, Gentile C, Gentile MD, et al. SARS-CoV-2 and the Host Cell: A Tale of Interactions. Front Virol. 2022 Jan 12;0:46. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004 Jun;203(2):631. Available from: /pmc/articles/PMC7167720/ Volz E, Hill V, McCrone JT, Price A, Jorgensen D, O’Toole Á, et al. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell. 2021 Jan 7;184(1):64. Available from: /pmc/articles/PMC7674007/ Tang T, Jaimes JA, Bidon MK, Straus MR, Daniel S, Whittaker GR. Proteolytic Activation of SARS-CoV-2 Spike at the S1/S2 Boundary: Potential Role of Proteases beyond Furin. ACS Infect Dis. 2021 Feb 12;7(2):264–72. Available from: https://pubs.acs.org/doi/full/10.1021/acsinfecdis.0c00701 Örd M, Faustova I, Loog M. 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. Sci Reports 2020 101. 2020 Oct 9;10(1):1–10. Available from: https://www.nature.com/articles/s41598-020-74101-0 Yang H, Rao Z. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nat Rev Microbiol 2021 1911. 2021 Sep 17;19(11):685–700. Available from: https://www.nature.com/articles/s41579-021-00630-8 Casari I, Manfredi M, Metharom P, Falasca M. Dissecting lipid metabolism alterations in SARS-CoV-2. Prog Lipid Res. 2021 Apr 1;82:101092. Klein S, Cortese M, Winter SL, Wachsmuth-Melm M, Neufeldt CJ, Cerikan B, et al. SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography. Nat Commun 2020 111. 2020 Nov 18;11(1):1–10. Available from: https://www.nature.com/articles/s41467-020-19619-7 Ma’ayan A. Complex systems biology. J R Soc Interface. 2017 Sep 1;14(134). Available from: /pmc/articles/PMC5636275/ Murray R, Granner D, Mayes P, Rodwell V. Bioquímica de Harper. 11a ed. D.F México: Editorial El Manual Moderno, S.A; 1988. 9 p. Macías Alvia A, Astudillo Hurtado JR, Holguín Cedeño DM, Vite Solórzano FA, Scott Álava MM, Vallejo Valdivieso PA, et al. INTRODUCCIÓN AL ESTUDIO DE LA BIOQUÍMICA. Editorial Área de Innovación y Desarrollo SL, editor. ALICANTE; 2018. 1–120 p. Lebeau G, Vagner D, Frumence É, Ah-Pine F, Guillot X, Nobécourt E, et al. Deciphering SARS-CoV-2 Virologic and Immunologic Features. Int J Mol Sci. 2020 Aug 2;21(16):1–40. Available from: /pmc/articles/PMC7460647/ Kell DB, Oliver SG. The metabolome 18 years on: a concept comes of age. Metabolomics. 2016 Oct 1;12(9). Available from: /pmc/articles/PMC5009154/ Alseekh S, Fernie AR. Metabolomics 20 years on: what have we learned and what hurdles remain? Plant J. 2018 Jun 1;94(6):933–42. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/tpj.13950 Bujak R, Struck-Lewicka W, Markuszewski MJ, Kaliszan R. Metabolomics for laboratory diagnostics. J Pharm Biomed Anal. 2015 Sep 10;113:108–20. Rinschen MM, Ivanisevic J, Giera M, Siuzdak G. Identification of bioactive metabolites using activity metabolomics. Nat Rev Mol Cell Biol. 2019 Jun 1;20(6):353. Available from: /pmc/articles/PMC6613555/ Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol. 2016 Jul 1;17(7):451. Available from: /pmc/articles/PMC5729912/ MetCore U. Acerca de metabolómica. Available from: https://metcore.uniandes.edu.co/es/acerca-de-metabolomica Seger C, Salzmann L. After another decade: LC–MS/MS became routine in clinical diagnostics. Clin Biochem. 2020 Aug 1;82:2–11. Li J, Zhu HJ. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters. Mol 2020, Vol 25, Page 2718. 2020 Jun 11;25(11):2718. Available from: https://www.mdpi.com/1420-3049/25/11/2718/htm Roberts LD, Souza AL, Gerszten RE, Clish CB. Targeted Metabolomics. Curr Protoc Mol Biol. 2012 Apr;CHAPTER(SUPPL.98):Unit30.2. Available from: /pmc/articles/PMC3334318/ Ochoa B. La lipidómica, una nueva herramienta al servicio de la salud. Gac Med Bilbao. 2006 Jun 6;103:101–2. Available from: https://www.elsevier.es/es-revista-gaceta-medica-bilbao-316-pdf-S0304485806745346 Yang K, Han X. Lipidomics: Techniques, applications, and outcomes related to biomedical sciences. Trends Biochem Sci. 2016 Nov 1;41(11):954. Available from: /pmc/articles/PMC5085849/ Meikle TG, Huynh K, Giles C, Meikle PJ. Clinical lipidomics: realizing the potential of lipid profiling. J Lipid Res. 2021;62. Available from: /pmc/articles/PMC8528718/ Horton R, Mora L, Scrimgeour G, Perry M, Rawn D. Principios de Bioquímica. 4a ed. Fuerte R, editor. México: Pearson education; 2008. Li A, Hines KM, Xu L. Lipidomics by HILIC-Ion Mobility-Mass Spectrometry. Methods Mol Biol. 2020;2084:119. Available from: /pmc/articles/PMC7255642/ Züllig T, Trötzmüller M, Köfeler HC. Lipidomics from sample preparation to data analysis: a primer. Anal Bioanal Chem. 2020 Apr 1;412(10):2191. Available from: /pmc/articles/PMC7118050/ Züllig T, Köfeler HC. High resolution mass spectrometry in lipidomics. Mass Spectrom Rev. 2021 May 1;40(3):162. Available from: /pmc/articles/PMC8049033/ Zhou B, Xiao JF, Tuli L, Ressom HW. LC-MS-based metabolomics. Mol Biosyst. 2012;8(2):470. Available from: /pmc/articles/PMC3699692/ Li W, Jie Z, Tse F. Handbook of LC-MS Bioanalysis: Best Practices, Experimental Protocols, and Regulations. Jhon Wiley. Canada; 2013. 704 p. Available from: https://books.google.com.co/books?id=yYOuAAAAQBAJ&printsec=frontcover&dq=LC-MS&hl=es&sa=X&redir_esc=y#v=onepage&q=LC-MS&f=false Barnes S, Benton HP, Casazza K, Cooper SJ, Cui X, Du X, et al. Training in metabolomics research. I. Designing the experiment, collecting and extracting samples and generating metabolomics data. J Mass Spectrom. 2016 Jul 1;51(7):461. Available from: /pmc/articles/PMC4964969/ Dunn WB, Wilson ID, Nicholls AW, Broadhurst D. The importance of experimental design and QC samples in large-scale and MS-driven untargeted metabolomic studies of humans. Bioanalysis. 2012 Sep;4(18):2249–64. Available from: https://pubmed.ncbi.nlm.nih.gov/23046267/ Lee AY, Troisi J, Symes SJK. Experimental design in metabolomics. Metabolomics Perspect. 2022 Jan 1;27–61. EMBL-EBI. Designing a metabolomics study. Available from: https://www.ebi.ac.uk/training/online/courses/metabolomics-introduction/designing-a-metabolomics-study/ Jacyna J, Kordalewska M, Markuszewski MJ. Design of Experiments in metabolomics-related studies: An overview. J Pharm Biomed Anal. 2019 Feb 5;164:598–606. Méndez Rodríguez KB, Santoyo Treviño MJ, Saldaña Villanueva K, Rodríguez Aguilar M, Flores Ramírez R, Pérez Vázquez FJ. Metabolomics as a new tool for timely diagnosis in noncommunicable diseases. Rev salud Ambient. 2019;19(2):109–15. Libiseller G, Dvorzak M, Kleb U, Gander E, Eisenberg T, Madeo F, et al. IPO: a tool for automated optimization of XCMS parameters. BMC Bioinformatics. 2015 Apr 16;16(1). Available from: /pmc/articles/PMC4404568/ Andaluz sociedad grupo regional analítica E de química. BOLETÍN GRASEQA Metabolómica. García Reyes JF, editor. 2012;56. Naz S, Moreira Dos Santos DC, García A, Barbas C. Analytical protocols based on LC-MS, GC-MS and CE-MS for nontargeted metabolomics of biological tissues. Bioanalysis. 2014;6(12):1657–77. Available from: https://pubmed.ncbi.nlm.nih.gov/25077626/ Mastrangelo A, Ferrarini A, Rey-Stolle F, García A, Barbas C. From sample treatment to biomarker discovery: A tutorial for untargeted metabolomics based on GC-(EI)-Q-MS. Anal Chim Acta. 2015 Nov 5;900:21–35. Jiye A, Trygg J, Gullberg J, Johansson AI, Jonsson P, Antti H, et al. Extraction and GC/MS analysis of the human blood plasma metabolome. Anal Chem. 2005 Dec 15;77(24):8086–94. Available from: https://pubmed.ncbi.nlm.nih.gov/16351159/ Garcia A, Barbas C. Gas chromatography-mass spectrometry (GC-MS)-based metabolomics. Methods Mol Biol. 2011;708:191–204. Available from: https://pubmed.ncbi.nlm.nih.gov/21207291/ Nishikaze T. Sialic acid derivatization for glycan analysis by mass spectrometry. Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(9):523. Available from: /pmc/articles/PMC6856002/ David V, Moldoveanu SC, Galaon T. Derivatization procedures and their analytical performances for HPLC determination in bioanalysis. Biomed Chromatogr. 2021 Jan 1;35(1):e5008. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/bmc.5008 Akula RK, Kwon YU. Bioenzymatic and Chemical Derivatization of Renewable Fatty Acids. Biomolecules. 2019 Oct 1;9(10). Available from: /pmc/articles/PMC6843907/ Marshall DD, Powers R. Beyond the Paradigm: Combining Mass Spectrometry and Nuclear Magnetic Resonance for Metabolomics. Prog Nucl Magn Reson Spectrosc. 2017 May 1;100:1. Available from: /pmc/articles/PMC5448308/ Perez HL, Evans CA. Chemical derivatization in bioanalysis. http://dx.doi.org/104155/bio15182. 2015 Nov 3;7(19):2435–7. Available from: https://www.future-science.com/doi/full/10.4155/bio.15.182 Domingues P, García A, Skrzydlewska E. Advanced Analytical Chemistry for Life Sciences. Bialystok: Liberlibro.com A.C.; Available from: https://www.umb.edu.pl/photo/pliki/projekty_umb/aac/aaclifesci-manual-spanish_with-cover.pdf Wu D, Shu T, Yang X, Song J-X, Zhang M, Yao C, et al. Plasma metabolomic and lipidomic alterations associated with COVID-19. Natl Sci Rev. 2020 Jul 1;7(7):1157–68. Available from: https://academic.oup.com/nsr/article/7/7/1157/5826189 Zheng F, Lin Y, Boulas P. Development and validation of a novel HILIC method for the quantification of low-levels of cuprizone in cuprizone-containing chow. Sci Reports 2021 111. 2021 Sep 9;11(1):1–10. Available from: https://www.nature.com/articles/s41598-021-97590-z Unsihuay D, Mesa Sanchez D, Laskin J. Quantitative Mass Spectrometry Imaging of Biological Systems. Annu Rev Phys Chem. 2021 Apr 20;72:307. Available from: /pmc/articles/PMC8161172/ Bantscheff M, Schirle M, Sweetman G, Rick J, Kuster B. Quantitative mass spectrometry in proteomics: a critical review. Anal Bioanal Chem 2007 3894. 2007 Aug 1;389(4):1017–31. Available from: https://link.springer.com/article/10.1007/s00216-007-1486-6 Han X, Aslanian A, Yates JR. Mass Spectrometry for Proteomics. Curr Opin Chem Biol. 2008 Oct ;12(5):483. Available from: /pmc/articles/PMC2642903/ Nauta SP, Poeze M, Heeren RMA, Porta Siegel T. Clinical use of mass spectrometry (imaging) for hard tissue analysis in abnormal fracture healing. Clin Chem Lab Med. 2020 Jun 1;58(6):897–913. Available from: https://www.degruyter.com/document/doi/10.1515/cclm-2019-0857/html Buchberger AR, DeLaney K, Johnson J, Li L. Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights. Anal Chem. 2018 Jan 2;90(1):240. Available from: /pmc/articles/PMC5959842/ Indelicato S, Bongiorno D, Ceraulo L. Recent Approaches for Chemical Speciation and Analysis by Electrospray Ionization (ESI) Mass Spectrometry. Front Chem. 2020 Jan 20;8:625945. Available from: /pmc/articles/PMC7855954/ Ryan DJ, Spraggins JM, Caprioli RM. Protein Identification Strategies in MALDI Imaging Mass Spectrometry: A Brief Review. Curr Opin Chem Biol. 2019 Feb 1;48:64. Available from: /pmc/articles/PMC6382520/ Milewska A, Ner-Kluza J, Dabrowska A, Bodzon-Kulakowska A, Pyrc K, Suder P. MASS SPECTROMETRY IN VIROLOGICAL SCIENCES. Mass Spectrom Rev. 2020 Sep 1;39(5–6):499–522. Available from: /pmc/articles/PMC7228374/ Pitt JJ. Principles and Applications of Liquid Chromatography-Mass Spectrometry in Clinical Biochemistry. Clin Biochem Rev. 2009 Feb;30(1):19. Available from: /pmc/articles/PMC2643089/ Fang Z, Gonzalez FJ. LC–MS‑based metabolomics: an update. Arch Toxicol. 2014;88(8):1491. Available from: /pmc/articles/PMC6310611/ Fiehn O. Metabolomics by Gas Chromatography-Mass Spectrometry: the combination of targeted and untargeted profiling. Curr Protoc Mol Biol. 2016 Apr 1;114:30.4.1. Available from: /pmc/articles/PMC4829120/ KK Pasikanti, PC Ho, EC Chan. Gas chromatography/mass spectrometry in metabolic profiling of biological fluids. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Aug 15;871(2):202–11. Available from: https://pubmed.ncbi.nlm.nih.gov/18479983/ UNLP F de CA y F-. INTRODUCCIÓN A LAS SEPARCIONES ANALÍTICAS. Available from: https://aulavirtual.agro.unlp.edu.ar/pluginfile.php/35288/mod_resource/content/1/2 cromatografia 2017.pdf JW H. Gas chromatography-mass spectrometry. Methods Mol Biol. 2006;324:53–74. Available from: https://pubmed.ncbi.nlm.nih.gov/16761371/ Gomis Yagües V. Tema 4. Cromatografía de líquidos de alta resolución. 2008. Available from: http://hdl.handle.net/10045/8248 Buszewski B, Noga S. Hydrophilic interaction liquid chromatography (HILIC)—a powerful separation technique. Anal Bioanal Chem. 2012 Jan;402(1):231. Available from: /pmc/articles/PMC3249561/ Boersema PJ, Mohammed S, Heck AJR. Hydrophilic interaction liquid chromatography (HILIC) in proteomics. Anal Bioanal Chem. 2008 May 9;391(1):151–9. Available from: https://link.springer.com/article/10.1007/s00216-008-1865-7 Paczkowska M, Mizera M, Tężyk A, Zalewski P, Dzitko J, Cielecka-Piontek J. Hydrophilic interaction chromatography (HILIC) for the determination of cetirizine dihydrochloride. Arab J Chem. 2019 Dec 1;12(8):4204–11. Harvey KA, Walker CL, Xu Z, Whitley P, Pavlina TM, Hise M, et al. Oleic acid inhibits stearic acid-induced inhibition of cell growth and pro-inflammatory responses in human aortic endothelial cells. J Lipid Res. 2010 Dec;51(12):3470. Available from: /pmc/articles/PMC2975719/ Stubbs BJ, Koutnik AP, Goldberg EL, Upadhyay V, Turnbaugh PJ, Verdin E, et al. Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections. Med (New York, N.y). 2020 Dec 12;1(1):43. Available from: /pmc/articles/PMC7362813/ Fahy E, Subramaniam S, Alex Brown H, Glass CK, Merrill AH, Murphy RC, et al. A comprehensive classification system for lipids1. J Lipid Res. 2005 May 1;46(5):839–61. Available from: http://www.jlr.org/article/S0022227520339687/fulltext Gomez-Gomez A, Rodríguez-Morató J, Haro N, Marín-Corral J, Masclans JR, Pozo OJ. Untargeted detection of the carbonyl metabolome by chemical derivatization and liquid chromatography-tandem mass spectrometry in precursor ion scan mode: Elucidation of COVID-19 severity biomarkers. Anal Chim Acta. 2022 Mar 1;1196. Available from: https://pubmed.ncbi.nlm.nih.gov/35151400/ Shi D, Yan R, Lv L, Jiang H, Lu Y, Sheng J, et al. The serum metabolome of COVID-19 patients is distinctive and predictive. Metabolism. 2021 May 1;118:154739. Available from: /pmc/articles/PMC7920809/ Landaas S, Jakobs C. The occurrence of 2-hydroxyisovaleric acid in patients with lactic acidosis and ketoacidosis. Clin Chim Acta. 1977 Aug 1;78(3):489–93. Available from: https://pubmed.ncbi.nlm.nih.gov/884872/ Patel U, Deluxe L, Salama C, Jimenez AR, Whiting A, Lubin C, et al. Evaluation of Characteristics and Outcomes for Patients with Diabetic Ketoacidosis (DKA) With and Without COVID-19 in Elmhurst Queens During Similar Three-Month Periods in 2019 and 2020. Cureus. 2021 Jul 16;13(7). Available from: /pmc/articles/PMC8364784/ Gupta GS. The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients. Inflammation. 2022 Dec 1;45(6):2091. Available from: /pmc/articles/PMC9117991/ Stromberg S, Baxter BA, Dooley G, LaVergne SM, Gallichotte E, Dutt T, et al. Relationships between plasma fatty acids in adults with mild, moderate, or severe COVID-19 and the development of post-acute sequelae. Front Nutr. 2022 Sep 14;9. Available from: /pmc/articles/PMC9515579/ Leonard J V. Recent advances in amino acid and organic acid metabolism. J Inherit Metab Dis. 2007 Apr;30(2):134–8. Available from: https://pubmed.ncbi.nlm.nih.gov/17237988/ Papagianni M. Organic Acids. Compr Biotechnol Second Ed. 2011 Jan 1;1:109–20. Rees CA, Rostad CA, Mantus G, Anderson EJ, Chahroudi A, Jaggi P, et al. Brief Report: Altered amino acid profile in patients with SARS-CoV-2 infection. Proc Natl Acad Sci U S A. 2021 Jun 6;118(25). Available from: /pmc/articles/PMC8237604/ Atila A, Alay H, Yaman ME, Akman TC, Cadirci E, Bayrak B, et al. The serum amino acid profile in COVID-19. Amino Acids. 2021 Oct 1;53(10):1569. Available from: /pmc/articles/PMC8487804/ Páez-Franco JC, Maravillas-Montero JL, Mejía-Domínguez NR, Torres-Ruiz J, Tamez-Torres KM, Pérez-Fragoso A, et al. Metabolomics analysis identifies glutamic acid and cystine imbalances in COVID-19 patients without comorbid conditions. Implications on redox homeostasis and COVID-19 pathophysiology. PLoS One. 2022 Sep 1;17(9). Available from: /pmc/articles/PMC9488784/ Kalyanaraman B. Reactive oxygen species, proinflammatory and immunosuppressive mediators induced in COVID-19: overlapping biology with cancer. RSC Chem Biol. 2021 Oct 10;2(5):1402. Available from: /pmc/articles/PMC8496060/ Laforge M, Elbim C, Frère C, Hémadi M, Massaad C, Nuss P, et al. Tissue damage from neutrophil-induced oxidative stress in COVID-19. Nat Rev Immunol. 2020 Sep 1;20(9):515. Available from: /pmc/articles/PMC7388427/ Kim HY, Lee H, Kim SH, Jin H, Bae J, Choi HK. Discovery of potential biomarkers in human melanoma cells with different metastatic potential by metabolic and lipidomic profiling. Sci Rep. 2017 Dec 1;7(1). Available from: /pmc/articles/PMC5562697/ Bharadwaj S, Singh M, Kirtipal N, Kang SG. SARS-CoV-2 and Glutamine: SARS-CoV-2 Triggered Pathogenesis via Metabolic Reprograming of Glutamine in Host Cells. Front Mol Biosci. 2021 Jan 11;7:462. Lieber C. Pathogenesis and treatment of alcoholic liver disease: progress over the last 50 years - PubMed. Rocz Akad Med Bialymst. 2005;50:7–20. Available from: https://pubmed.ncbi.nlm.nih.gov/16363067/ McMenamy RH, Vang J, Drapanas T. Amino acid and alpha-keto acid concentrations in plasma and blood of the liverless dog. Am J Physiol. 1965;209(5):1046–52. Available from: https://pubmed.ncbi.nlm.nih.gov/5849485/ Yudkoff M, Blazer-Yost B, Cohn R, Segal S. On the clinical significance of the plasma alpha-amino-n-butyric acid:leucine ratio. Am J Clin Nutr. 1979;32(2):282–5. Available from: https://pubmed.ncbi.nlm.nih.gov/420125/ Darling PB, Grunow J, Rafii M, Brookes S, Ball RO, Pencharz PB. Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans. Am J Physiol Endocrinol Metab. 2000;278(5). Available from: https://pubmed.ncbi.nlm.nih.gov/10780944/ Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG. Free amino acid and dipeptide changes in the body fluids from Alzheimer’s disease subjects. Amino Acids. 2007 Feb;32(2):213–24. Available from: https://pubmed.ncbi.nlm.nih.gov/17031479/ Yang J, Chen T, Sun L, Zhao Z, Qi X, Zhou K, et al. Potential metabolite markers of schizophrenia. Mol Psychiatry. 2013 Jan;18(1):67. Available from: /pmc/articles/PMC3526727/ Ni Y, Xie G, Jia W. Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery. J Proteome Res. 2014 Sep 5;13(9):3857–70. Available from: https://pubmed.ncbi.nlm.nih.gov/25105552/ Cheng Y, Xie G, Chen T, Qiu Y, Zou X, Zheng M, et al. Distinct urinary metabolic profile of human colorectal cancer. J Proteome Res. 2012 Feb 3;11(2):1354–63. Available from: https://pubmed.ncbi.nlm.nih.gov/22148915/ Woo HI, Chun MR, Yang JS, Lim SW, Kim MJ, Kim SW, et al. Plasma Amino Acid Profiling in Major Depressive Disorder Treated With Selective Serotonin Reuptake Inhibitors. CNS Neurosci Ther. 2015 May 1;21(5):417. Available from: /pmc/articles/PMC6495833/ Adachi Y, Toyoshima K, Nishimoto R, Ueno S, Tanaka T, Imaizumi A, et al. Association between plasma α-aminobutyric acid and depressive symptoms in older community-dwelling adults in Japan. Geriatr Gerontol Int. 2019 Mar 1;19(3):254–8. Available from: https://pubmed.ncbi.nlm.nih.gov/30561103/ Chiarla C, Giovannini I, Siegel JH. Characterization of alpha-amino-n-butyric acid correlations in sepsis. Transl Res. 2011;158(6):328–33. Available from: https://pubmed.ncbi.nlm.nih.gov/22061040/ Lee YK, Chang WC, Prakash E, Peng YJ, Tu Z, Lin CH, et al. Carbohydrate Ligands for COVID-19 Spike Proteins. Viruses. 2022 Feb 1;14(2). Available from: /pmc/articles/PMC8880561/ Del-Corso A, Cappiello M, Moschini R, Balestri F, Mura U, Ipata PL. The furanosidic scaffold of d-ribose: a milestone for cell life. Biochem Soc Trans. 2019 Dec 20;47(6):1931–40. Available from: /biochemsoctrans/article/47/6/1931/221031/The-furanosidic-scaffold-of-d-ribose-a-milestone Alhammad YMO, Kashipathy MM, Roy A, Gagné J-P, McDonald P, Gao P, et al. The SARS-CoV-2 Conserved Macrodomain Is a Mono-ADP-Ribosylhydrolase. J Virol. 2021 Jan 13;95(3). Available from: /pmc/articles/PMC7925111/ Frick DN, Virdi RS, Vuksanovic N, Dahal N, Silvaggi NR. Molecular Basis for ADP-Ribose Binding to the Mac1 Domain of SARS-CoV-2 nsp3. Biochemistry. 2020 Jul 21;59(28):2608–15. Available from: /pmc/articles/PMC7341687/ Li Y, Zhang D, Gao X, Wang X, Zhang L. 2′- and 3′-Ribose Modifications of Nucleotide Analogues Establish the Structural Basis to Inhibit the Viral Replication of SARS-CoV-2. J Phys Chem Lett. 2022;4111–8. Noguchi C, Kamitori K, Hossain A, Hoshikawa H, Katagi A, Dong Y, et al. D-Allose Inhibits Cancer Cell Growth by Reducing GLUT1 Expression. Tohoku J Exp Med. 2016 Jan 30;238(2):131–41. Gao D, Kawai N, Nakamura T, Lu F, Fei Z, Tamiya T. Anti-inflammatory Effect of D-Allose in Cerebral Ischemia/Reperfusion Injury in Rats. Neurol Med Chir (Tokyo). 2013;53(6):365–74. Lv L, Jiang H, Chen Y, Gu S, Xia J, Zhang H, et al. The faecal metabolome in COVID-19 patients is altered and associated with clinical features and gut microbes. Anal Chim Acta. 2021 Apr 1;1152:338267. Available from: /pmc/articles/PMC7847702/ Zhao J, Zhang G, Zhang Y, Yi D, Li Q, Ma L, et al. 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides: SARS-CoV-2 RNA-dependent RNA polymerase inhibitors. Antiviral Res. 2021 Dec 1;196:105209. Available from: /pmc/articles/PMC8600920/ Matchett WH. Inhibition of Tryptophan Synthetase by Indoleacrylic Acid. J Bacteriol. 1972 Apr;110(1):146. Available from: /pmc/articles/PMC247391/?report=abstract Wlodarska M, Luo C, Kolde R, d’Hennezel E, Annand JW, Heim CE, et al. Indoleacrylic acid produced by commensal Peptostreptococcus species suppresses inflammation. Cell Host Microbe. 2017 Jul 7;22(1):25. Available from: /pmc/articles/PMC5672633/ Espadinha M, Barcherini V, Gonçalves LM, Molins E, Antunes AMM, Santos MMM. Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma. Pharmaceuticals. 2021 Mar 1;14(3):208. Available from: /pmc/articles/PMC8001353/ Fawazy NG, Panda SS, Mostafa A, Kariuki BM, Bekheit MS, Moatasim Y, et al. Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties. Sci Rep. 2022 Dec 1;12(1):13880. Available from: /pmc/articles/PMC9380671/ Jochum M, Lee MD, Curry K, Zaksas V, Vitalis E, Treangen T, et al. Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease. Sci Rep. 2022 Dec 1;12(1). Available from: /pmc/articles/PMC9729217/ Chowdhury P, Pathak P. Neuroprotective immunity by essential nutrient “Choline” for the prevention of SARS CoV2 infections: An in silico study by molecular dynamics approach. Chem Phys Lett. 2020 Dec 12;761:138057. Available from: /pmc/articles/PMC7532804/ Orfei MD, Porcari DE, D’Arcangelo S, Maggi F, Russignaga D, Ricciardi E. A New Look on Long-COVID Effects: The Functional Brain Fog Syndrome. J Clin Med. 2022 Oct 1;11(19). Available from: /pmc/articles/PMC9573330/ Al-kuraishy HM, Al-Buhadily AK, Al-Gareeb AI, Alorabi M, Hadi Al-Harcan NA, El-Bouseary MM, et al. Citicoline and COVID-19: vis-à-vis conjectured. Naunyn-Schmiedeberg’s Arch Pharmacol 2022 39512. 2022 Sep 5;395(12):1463–75. Available from: https://link.springer.com/article/10.1007/s00210-022-02284-6 Feher J. Pancreatic and Biliary Secretion. Quant Hum Physiol. 2012 Jan 1;721–30. Thuy PX, Bao TDD, Moon EY. Ursodeoxycholic acid ameliorates cell migration retarded by the SARS-CoV-2 spike protein in BEAS-2B human bronchial epithelial cells. Biomed Pharmacother. 2022 Jun 1;150:113021. Available from: /pmc/articles/PMC9035373/ |
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Atribución-NoComercial-SinDerivadas 4.0 Internacional |
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Universidad Nacional de Colombia |
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Bogotá - Ciencias - Maestría en Ciencias - Bioquímica |
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Facultad de Ciencias |
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Bogotá, Colombia |
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Universidad Nacional de Colombia - Sede Bogotá |
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Universidad Nacional de Colombia |
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Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Sandoval Hernández, Adrián Gabrielc6996deb221d930e2db873621dbffb44Cala Molina, Monica Patriciab01869ac7e69ffb2f562f1fb8c6b9a85Gómez Muñoz, Laura Alejandra8dbea7a31fae9d462720fa06731acf74Arboleda Granados HumbertoSantamaria Torres Mary AndreaGómez Muñoz Lilia NatalyMuerte CelularGómez-Muñoz, L. A2023-09-05T20:11:57Z2023-09-05T20:11:57Z2022-12-20https://repositorio.unal.edu.co/handle/unal/84652Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, diagramasIntroducción: Recientemente la enfermedad por el coronavirus SARS-CoV-2, denominada COVID-19, se convirtió en pandemia causando más de 6,38 millones de muertes en el mundo, y en Colombia más de 6,3 millones de casos con más de 142 mil fallecidos, con una tasa de letalidad del 2,5 %. La enfermedad se caracterizó por presentar una prognosis heterogénea con una baja predictibilidad y elevada mortalidad. Objetivo: Evaluar la relación entre el espectro clínico de la COVID 19 y los cambios en el metaboloma del plasma sanguíneo de sujetos positivos para SARS-CoV-2 en una población bogotana. Metodología: Se recolectaron 100 muestras de plasma sanguíneo en colaboración con la Clínica Colsanitas y Unisanitas, agrupados según sus características clínicas en grupos leve, moderado y severo, más un grupo control. El análisis metabolómico y lipidómico multiplataforma no dirigido se realizó por GC/MS y LC/MS en MetCore, de la Universidad de los Andes, los análisis estadísticos se realizaron usando MetaboAnalyst 5.0 y el paquete deducer del software R. Resultados y análisis: Se encontraron 148 metabolitos alterados entre los grupos experimentales, incluyendo carbohidratos como la ribosa, alosa y manitol, lípidos como las fosfocolinas, lisofosfocolinas, lisofosfatidilcolinas y aminoácidos como lisina, acido glutámico y aminobutanoico, asociados con falla multiorgánica y procesos inflamatorios. Conclusiones: Los metabolitos encontrados en este estudio correlacionan con los reportados para otras poblaciones como europeas y asiáticas. Se identificaron incrementados en casos severos el ácido glutámico, el ácido 2-hidroxi-3-metilbutírico, y disminuida la ribosa que podría considerarse factores pronósticos de estado crítico para COVID-19. (Texto tomado de la fuente)Introduction: Recently, the SARS-CoV-2 coronavirus disease called COVID-19 became a pandemic, causing 6.38 million deaths worldwide. In Colombia, there have been 6.3 million cases and 142,000 deaths, with a rate lethality of 2.5%. The disease was characterized by presenting a heterogeneous prognosis with low predictability and high mortality. Objective: To record metabolomic changes in a group of SARS-CoV-2 positive patients at clinical onset as potential markers of severe COVID-19 disease progression. Methodology: 100 blood plasma samples were collected in collaboration with Colsanitas hospital and Unisanitas, grouped according to their clinical characteristics into mild, moderate, and severe groups, plus a control group. Non-targeted cross-platform metabolomic and lipidomic analysis was performed by GC/MS and LC/MS at MetCore, Andes university, and statistical analyzes were performed using MetaboAnalyst 5.0 and the R software deducer package. Results and analysis: 148 altered metabolites were found between the experimental groups, including carbohydrates such as ribose, allose and mannitol, lipids such as phosphocholines, lysophosphocholines, lysophosphaditylcholines and amino acids such as lysine, glutamic and aminobutanoic acid, associated with multiple organ failure and inflammatory processes. Conclusion: The metabolites found in this study correlate with those reported for other populations, such as Europeans and Asians. Increased glutamic acid, 2-hydroxy-3-methylbutyric acid, and decreased ribose were identified in severe cases, which could be considered critical prognostic factors for COVID-19.MaestríaMagíster en Ciencias - Bioquímicaxxii, 154 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - BioquímicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá570 - Biología::572 - Bioquímica610 - Medicina y salud::616 - Enfermedades540 - Química y ciencias afines::543 - Química analíticaCOVID-19SARS-CoV-2MetabolomicsLipidomicsPrognostic factorsMetabolómicaLipidómicaFactores pronósticosEvaluación del perfil metabolómico y su relación con el espectro clínico de sujetos positivos para SARS-CoV-2 en una población bogotanaEvaluation of the metabolomic profile and its relationship with the clinical spectrum of positive subjects for SARS-COV-2 in a Bogota populationTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMAlsharif W, Qurashi A. Effectiveness of COVID-19 diagnosis and management tools: A review. Radiogr (London, Engl 1995). 2021 May 1;27(2):682. Available from: /pmc/articles/PMC7505601/COVID Live Update: Cases and Deaths from the Coronavirus - Worldometer. Available from: https://www.worldometers.info/coronavirus/?utm_campaign=homeAdvegas1?El Coronavirus en Colombia. Available from: https://coronaviruscolombia.gov.co/Covid19/index.htmlOMS O mundial de la salud. Nuevo coronavirus 2019. Available from: https://www.who.int/es/emergencies/diseases/novel-coronavirus-2019?gclid=EAIaIQobChMI_8TIx6iE9AIViYKGCh0H1ADqEAAYASAAEgLfDPD_BwEJiang S, Hillyer C, Du L. Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses. Trends Immunol2020 May 1;41(5):355. Available from: /pmc/articles/PMC7129017/Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England). 2020 Feb 15;395(10223):497. Available from: /pmc/articles/PMC7159299/Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat Nanotechnol. 2020 Apr 1;15(4):1. Available from: /pmc/articles/PMC7094976/OMS. La OMS interrumpe los grupos de tratamiento de la COVID-19 con hidroxicloroquina y con la combinación lopinavir/ritonavir. Available from: https://www.who.int/es/news/item/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect Dis. 2021 Jan 1;21(1):39. Available from: /pmc/articles/PMC7561304/Thanh Le T, Andreadakis Z, Kumar A, Gómez Román R, Tollefsen S, Saville M, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov. 2020 May 1;19(5):305–6.Ura T, Yamashita A, Mizuki N, Okuda K, Shimada M. New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates. Vaccine. 2021 Jan 8;39(2):197. Available from: /pmc/articles/PMC7685034/Chakraborty S, Mallajosyula V, Tato CM, Tan GS, Wang TT. SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand? Adv Drug Deliv Rev. 2021 May 1;172:314. Available from: /pmc/articles/PMC7816567/OMS. Enfermedad por el coronavirus (COVID-19): Vacunas. Available from: https://www.who.int/es/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-(covid-19)-vaccines?adgroupsurvey=%7Badgroupsurvey%7D&gclid=Cj0KCQiAi9mPBhCJARIsAHchl1xgy5gL27gOo_lHlJ7Je7rmbUnhm8OQcOJwqZrFxb2yXkrVOMS. Lo que debe saber sobre la vacuna de Pfizer-BioNTech (BNT162b2) contra la COVID-19. Available from: https://www.who.int/es/news-room/feature-stories/detail/who-can-take-the-pfizer-biontech-covid-19--vaccine-what-you-need-to-knowAwadasseid A, Wu Y, Tanaka Y, Zhang W. Current advances in the development of SARS-CoV-2 vaccines. Int J Biol Sci. 2021;17(1):8. Available from: /pmc/articles/PMC7757035/Baig AM. Computing the Effects of SARS-CoV-2 on RespirationRegulatory Mechanisms in COVID-19. ACS Chem Neurosci. 2020 Aug 19;11(16):2416. Available from: /pmc/articles/PMC7422910/Irabien-Ortiz Á, Carreras-Mora J, Sionis A, Pàmies J, Montiel J, Tauron M. Fulminant myocarditis due to COVID-19. Rev Española Cardiol (English Ed. 2020 Jun 1;73(6):503–4. Available from: http://www.revespcardiol.org/en-fulminant-myocarditis-due-covid-19-articulo-S1885585720301651Garot J, Amour J, Pezel T, Dermoch F, Messadaa K, Felten M-L, et al. SARS-CoV-2 Fulminant Myocarditis. JACC Case Reports. 2020 Jul;2(9):1342. Available from: /pmc/articles/PMC7274592/Gauchotte G, Venard V, Segondy M, Cadoz C, Esposito-Fava A, Barraud D, et al. SARS-Cov-2 fulminant myocarditis: an autopsy and histopathological case study. Int J Legal Med. 2021 Mar 1;135(2):1. Available from: /pmc/articles/PMC7779100/Schrimpe-Rutledge AC, Codreanu SG, Sherrod SD, McLean JA. Untargeted metabolomics strategies – Challenges and Emerging Directions. J Am Soc Mass Spectrom. 2016 Dec 1;27(12):1897. Available from: /pmc/articles/PMC5110944/Jang C, Chen L, Rabinowitz JD. Metabolomics and isotope tracing. Cell. 2018 May 3;173(4):822. Available from: /pmc/articles/PMC6034115/Sreepadmanabh M, Sahu AK, Chande A. COVID-19: Advances in diagnostic tools, treatment strategies, and vaccine development. J Biosci. 2020 Dec 1;45(1). Available from: /pmc/articles/PMC7683586/V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 2020 193. 2020 Oct 28;19(3):155–70. Available from: https://www.nature.com/articles/s41579-020-00468-6Naqvi AAT, Fatima K, Mohammad T, Fatima U, Singh IK, Singh A, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165878. Available from: /pmc/articles/PMC7293463/B Hu, H Guo, P Zhou, ZL Shi. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021 Mar 1;19(3):141–54. Available from: https://pubmed.ncbi.nlm.nih.gov/33024307/Chung JY, Thone MN, Kwon YJ. COVID-19 vaccines: The status and perspectives in delivery points of view. Adv Drug Deliv Rev. 2021 Mar 1;170:1. Available from: /pmc/articles/PMC7759095/Ahn D-G, Shin H-J, Kim M-H, Lee S, Kim H-S, Myoung J, et al. Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19). J Microbiol Biotechnol. 2020 Mar 28;30(3):313–24. Available from: https://www.jmb.or.kr/journal/view.html?doi=10.4014/jmb.2003.03011Gao Z, Xu Y, Sun C, Wang X, Guo Y, Qiu S, et al. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect. 2021 Feb 1;54(1):12. Available from: /pmc/articles/PMC7227597/Organization PAH. Epidemiological Update: Coronavirus disease (COVID-19). Pan Am Heal Organ. 2021 Aug 21; Available from: https://iris.paho.org/handle/10665.2/54717Atzrodt CL, Maknojia I, McCarthy RDP, Oldfield TM, Po J, Ta KTL, et al. A Guide to COVID‐19: a global pandemic caused by the novel coronavirus SARS‐CoV‐2. Febs J. 2020 Sep 1;287(17):3633–50. Available from: /pmc/articles/PMC7283703/?report=abstractOMS. Seguimiento de las variantes del SARS-CoV-2. 2021. Available from: https://www.who.int/es/activities/tracking-SARS-CoV-2-variants/tracking-SARS-CoV-2-variantsYan W, Zheng Y, Zeng X, He B, Cheng W. Structural biology of SARS-CoV-2: open the door for novel therapies. Signal Transduct Target Ther 2022 71. 2022 Jan 27;7(1):1–28. Available from: https://www.nature.com/articles/s41392-022-00884-5Instituto Nacional de salud de C. Noticias coronavirus-casos. 2021. Available from: https://www.ins.gov.co/Noticias/Paginas/coronavirus-casos.aspxInstituto Nacional de salud de C. COVID-19 en Colombia, Reporte diario. 2022. Available from: https://www.ins.gov.co/Noticias/paginas/coronavirus.aspxOrganización Panamericana de la Salud (OPS). REPORTE: Situación COVID-19 Colombia. 2022.Fehr AR, Perlman S. Coronaviruses: An Overview of Their Replication and Pathogenesis. Coronaviruses. 2015 Feb 26;1282:1. Available from: /pmc/articles/PMC4369385/Wang F, Kream RM, Stefano GB. An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development. Med Sci Monit. 2020;26:e924700-1. Available from: /pmc/articles/PMC7218962/Hardenbrook NJ, Zhang P. A structural view of the SARS-CoV-2 virus and its assembly. Curr Opin Virol. 2022 Feb 1;52:123–34.Ke Z, Oton J, Qu K, Cortese M, Zila V, McKeane L, et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions. Nat 2020 5887838. 2020 Aug 17;588(7838):498–502. Available from: https://www.nature.com/articles/s41586-020-2665-2Alfonso Accinelli R, Zhang Xu CM, Ju Wang J-D, Yachachin-Chávez JM, Cáceres-Pizarro JA, Tafur-Bances KB, et al. COVID-19: LA PANDEMIA POR EL NUEVO VIRUS SARS-CoV-2. Rev Peru Med Exp Salud Publica. 2020 Apr 20;37(2):302–11. Available from: https://www.scielosp.org/pdf/rpmesp/2020.v37n2/302-311/esKirtipal N, Bharadwaj S, Kang SG. From SARS to SARS-CoV-2, insights on structure, pathogenicity and immunity aspects of pandemic human coronaviruses. Infect Genet Evol. 2020 Nov 1;85:104502. Available from: /pmc/articles/PMC7425554/Benavides-Rosero MF, Benavides-Rosero MF. COVID-19 y la pandemia global causada por un nuevo coronavirus. Univ y Salud. 2020 Dec 10;22(3):299–314. Available from: http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0124-71072020000400299&lng=en&nrm=iso&tlng=esHarrison AG, Lin T, Wang P. Mechanisms of SARS-CoV-2 Transmission and Pathogenesis. Trends Immunol. 2020 Dec 1;41(12):1100. Available from: /pmc/articles/PMC7556779/Arya R, Kumari S, Pandey B, Mistry H, Bihani SC, Das A, et al. Structural insights into SARS-CoV-2 proteins. J Mol Biol. 2021 Jan 22;433(2):166725. Available from: /pmc/articles/PMC7685130/Giovanetti M, Benedetti F, Campisi G, Ciccozzi A, Fabris S, Ceccarelli G, et al. Evolution patterns of SARS-CoV-2: Snapshot on its genome variants. Biochem Biophys Res Commun. 2021 Jan 29;538:88. Available from: /pmc/articles/PMC7836704/Flower TG, Buffalo CZ, Hooy RM, Allaire M, Ren X, Hurley JH. Structure of SARS-cov-2 ORF8, a rapidly evolving immune evasion protein. Proc Natl Acad Sci U S A. 2021 Jan 12;118(2). Available from: /pmc/articles/PMC7812859/Huang Y, Yang C, Xu X feng, Xu W, Liu S wen. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin 2020 419. 2020 Aug 3;41(9):1141–9. Available from: https://www.nature.com/articles/s41401-020-0485-4Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol 2021 231. 2021 Oct 5;23(1):3–20. Available from: https://www.nature.com/articles/s41580-021-00418-xGroves DC, Rowland-Jones SL, Angyal A. The D614G mutations in the SARS-CoV-2 spike protein: Implications for viral infectivity, disease severity and vaccine design. Biochem Biophys Res Commun. 2021 Jan 29;538:104. Available from: /pmc/articles/PMC7643658/Zhang J, Cai Y, Xiao T, Lu J, Peng H, Sterling SM, et al. Structural impact on SARS-CoV-2 spike protein by D614G substitution. Science. 2021 Apr 30;372(6541):525. Available from: /pmc/articles/PMC8139424/Wang MY, Zhao R, Gao LJ, Gao XF, Wang DP, Cao JM. SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development. Front Cell Infect Microbiol. 2020 Nov 25;10. Available from: /pmc/articles/PMC7723891/Zhou P, Yang X Lou, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar 12;579(7798):270. Available from: /pmc/articles/PMC7095418/Scialo F, Daniele A, Amato F, Pastore L, Matera MG, Cazzola M, et al. ACE2: The Major Cell Entry Receptor for SARS-CoV-2. Lung. 2020 Dec 1;198(6):867. Available from: /pmc/articles/PMC7653219/Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020 May 28;581(7809):465–9. Available from: https://pubmed.ncbi.nlm.nih.gov/32235945/Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020 May 28;181(5):1016. Available from: /pmc/articles/PMC7252096/Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020 Dec 1;12(1). Available from: /pmc/articles/PMC7039956/Suryamohan K, Diwanji D, Stawiski EW, Gupta R, Miersch S, Liu J, et al. Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2. Commun Biol 2021 41. 2021 Apr 12;4(1):1–11. Available from: https://www.nature.com/articles/s42003-021-02030-3Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet (London, England). 2020 Feb 22;395(10224):565. Available from: /pmc/articles/PMC7159086/Mariano G, Farthing RJ, Lale-Farjat SLM, Bergeron JRC. Structural Characterization of SARS-CoV-2: Where We Are, and Where We Need to Be. Front Mol Biosci. 2020 Dec 17;7:344.Li C, Lee A, Grigoryan L, Arunachalam PS, Scott MKD, Trisal M, et al. Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine. Nat Immunol. 2022 Apr 1;23(4):543. Available from: /pmc/articles/PMC8989677/Tian JH, Patel N, Haupt R, Zhou H, Weston S, Hammond H, et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021 Dec 1;12(1). Available from: /pmc/articles/PMC7809486/Xia X. Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design. Viruses. 2021 Jan 1;13(1). Available from: /pmc/articles/PMC7829931/Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603–15. Available from: /pmc/articles/PMC7745181/Kang YF, Sun C, Zhuang Z, Yuan RY, Zheng Q, Li JP, et al. Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates. ACS Nano. 2021 Feb 23;15(2):2738–52. Available from: /pmc/articles/PMC7839421/Yadav R, Chaudhary JK, Jain N, Chaudhary PK, Khanra S, Dhamija P, et al. Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19. Cells. 2021 Apr 1;10(4). Available from: /pmc/articles/PMC8067447/Lu S, Ye Q, Singh D, Cao Y, Diedrich JK, Yates JR, et al. The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein. Nat Commun. 2021 Dec 1;12(1). Available from: /pmc/articles/PMC7820290/Wang W, Chen J, Yu X, Lan HY. Signaling mechanisms of SARS-CoV-2 Nucleocapsid protein in viral infection, cell death and inflammation. Int J Biol Sci. 2022;18(12):4704. Available from: /pmc/articles/PMC9305276/Karjee S, Mukherjee SK. RNAi suppressor: The hidden weapon of SARS-CoV. J Biosci. 2020 Dec 1;45(1). Available from: /pmc/articles/PMC7363689/Kadam SB, Sukhramani GS, Bishnoi P, Pable AA, Barvkar VT. SARS‐CoV‐2, the pandemic coronavirus: Molecular and structural insights. J Basic Microbiol. 2021 Mar 1;61(3):180. Available from: /pmc/articles/PMC8013332/Cao Y, Yang R, Lee I, Zhang W, Sun J, Wang W, et al. Characterization of the SARS‐CoV‐2 E Protein: Sequence, Structure, Viroporin, and Inhibitors. Protein Sci. 2021 Jun 1;30(6):1114. Available from: /pmc/articles/PMC8138525/Noori R, Sardar M. An outlook on potential protein targets of COVID-19 as a druggable site. Mol Biol Rep [Internet]. 2022 Nov 1;49(11):10729–48. Available from: https://link.springer.com/article/10.1007/s11033-022-07724-3Zhang Z, Nomura N, Muramoto Y, Ekimoto T, Uemura T, Liu K, et al. Structure of SARS-CoV-2 membrane protein essential for virus assembly. Nat Commun 2022 131. 2022 Aug 5;13(1):1–12. Available from: https://www.nature.com/articles/s41467-022-32019-3Shen L, Bard JD, Triche TJ, Judkins AR, Biegel JA, Gai X. Emerging variants of concern in SARS-CoV-2 membrane protein: a highly conserved target with potential pathological and therapeutic implications. Emerg Microbes Infect. 2021;10(1):885. Available from: /pmc/articles/PMC8118436/Hu Y, Wen J, Tang L, Zhang H, Zhang X, Li Y, et al. The M Protein of SARS-CoV: Basic Structural and Immunological Properties. Genomics Proteomics Bioinformatics. 2003;1(2):118. Available from: /pmc/articles/PMC5172243/Sui L, Zhao Y, Wang W, Wu P, Wang Z, Yu Y, et al. SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1. Front Immunol. 2021 May 18;12. Available from: /pmc/articles/PMC8168463/Thomas S. The Structure of the Membrane Protein of SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET. Pathog Immun [Internet]. 2020;5(1):342. Available from: /pmc/articles/PMC7608487/Pizzato M, Baraldi C, Boscato Sopetto G, Finozzi D, Gentile C, Gentile MD, et al. SARS-CoV-2 and the Host Cell: A Tale of Interactions. Front Virol. 2022 Jan 12;0:46.Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004 Jun;203(2):631. Available from: /pmc/articles/PMC7167720/Volz E, Hill V, McCrone JT, Price A, Jorgensen D, O’Toole Á, et al. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell. 2021 Jan 7;184(1):64. Available from: /pmc/articles/PMC7674007/Tang T, Jaimes JA, Bidon MK, Straus MR, Daniel S, Whittaker GR. Proteolytic Activation of SARS-CoV-2 Spike at the S1/S2 Boundary: Potential Role of Proteases beyond Furin. ACS Infect Dis. 2021 Feb 12;7(2):264–72. Available from: https://pubs.acs.org/doi/full/10.1021/acsinfecdis.0c00701Örd M, Faustova I, Loog M. 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. Sci Reports 2020 101. 2020 Oct 9;10(1):1–10. Available from: https://www.nature.com/articles/s41598-020-74101-0Yang H, Rao Z. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nat Rev Microbiol 2021 1911. 2021 Sep 17;19(11):685–700. Available from: https://www.nature.com/articles/s41579-021-00630-8Casari I, Manfredi M, Metharom P, Falasca M. Dissecting lipid metabolism alterations in SARS-CoV-2. Prog Lipid Res. 2021 Apr 1;82:101092.Klein S, Cortese M, Winter SL, Wachsmuth-Melm M, Neufeldt CJ, Cerikan B, et al. SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography. Nat Commun 2020 111. 2020 Nov 18;11(1):1–10. Available from: https://www.nature.com/articles/s41467-020-19619-7Ma’ayan A. Complex systems biology. J R Soc Interface. 2017 Sep 1;14(134). Available from: /pmc/articles/PMC5636275/Murray R, Granner D, Mayes P, Rodwell V. Bioquímica de Harper. 11a ed. D.F México: Editorial El Manual Moderno, S.A; 1988. 9 p.Macías Alvia A, Astudillo Hurtado JR, Holguín Cedeño DM, Vite Solórzano FA, Scott Álava MM, Vallejo Valdivieso PA, et al. INTRODUCCIÓN AL ESTUDIO DE LA BIOQUÍMICA. Editorial Área de Innovación y Desarrollo SL, editor. ALICANTE; 2018. 1–120 p.Lebeau G, Vagner D, Frumence É, Ah-Pine F, Guillot X, Nobécourt E, et al. Deciphering SARS-CoV-2 Virologic and Immunologic Features. Int J Mol Sci. 2020 Aug 2;21(16):1–40. Available from: /pmc/articles/PMC7460647/Kell DB, Oliver SG. The metabolome 18 years on: a concept comes of age. Metabolomics. 2016 Oct 1;12(9). Available from: /pmc/articles/PMC5009154/Alseekh S, Fernie AR. Metabolomics 20 years on: what have we learned and what hurdles remain? Plant J. 2018 Jun 1;94(6):933–42. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/tpj.13950Bujak R, Struck-Lewicka W, Markuszewski MJ, Kaliszan R. Metabolomics for laboratory diagnostics. J Pharm Biomed Anal. 2015 Sep 10;113:108–20.Rinschen MM, Ivanisevic J, Giera M, Siuzdak G. Identification of bioactive metabolites using activity metabolomics. Nat Rev Mol Cell Biol. 2019 Jun 1;20(6):353. Available from: /pmc/articles/PMC6613555/Johnson CH, Ivanisevic J, Siuzdak G. Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol. 2016 Jul 1;17(7):451. Available from: /pmc/articles/PMC5729912/MetCore U. Acerca de metabolómica. Available from: https://metcore.uniandes.edu.co/es/acerca-de-metabolomicaSeger C, Salzmann L. After another decade: LC–MS/MS became routine in clinical diagnostics. Clin Biochem. 2020 Aug 1;82:2–11.Li J, Zhu HJ. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters. Mol 2020, Vol 25, Page 2718. 2020 Jun 11;25(11):2718. Available from: https://www.mdpi.com/1420-3049/25/11/2718/htmRoberts LD, Souza AL, Gerszten RE, Clish CB. Targeted Metabolomics. Curr Protoc Mol Biol. 2012 Apr;CHAPTER(SUPPL.98):Unit30.2. Available from: /pmc/articles/PMC3334318/Ochoa B. La lipidómica, una nueva herramienta al servicio de la salud. Gac Med Bilbao. 2006 Jun 6;103:101–2. Available from: https://www.elsevier.es/es-revista-gaceta-medica-bilbao-316-pdf-S0304485806745346Yang K, Han X. Lipidomics: Techniques, applications, and outcomes related to biomedical sciences. Trends Biochem Sci. 2016 Nov 1;41(11):954. Available from: /pmc/articles/PMC5085849/Meikle TG, Huynh K, Giles C, Meikle PJ. Clinical lipidomics: realizing the potential of lipid profiling. J Lipid Res. 2021;62. Available from: /pmc/articles/PMC8528718/Horton R, Mora L, Scrimgeour G, Perry M, Rawn D. Principios de Bioquímica. 4a ed. Fuerte R, editor. México: Pearson education; 2008.Li A, Hines KM, Xu L. Lipidomics by HILIC-Ion Mobility-Mass Spectrometry. Methods Mol Biol. 2020;2084:119. Available from: /pmc/articles/PMC7255642/Züllig T, Trötzmüller M, Köfeler HC. Lipidomics from sample preparation to data analysis: a primer. Anal Bioanal Chem. 2020 Apr 1;412(10):2191. Available from: /pmc/articles/PMC7118050/Züllig T, Köfeler HC. High resolution mass spectrometry in lipidomics. Mass Spectrom Rev. 2021 May 1;40(3):162. Available from: /pmc/articles/PMC8049033/Zhou B, Xiao JF, Tuli L, Ressom HW. LC-MS-based metabolomics. Mol Biosyst. 2012;8(2):470. Available from: /pmc/articles/PMC3699692/Li W, Jie Z, Tse F. Handbook of LC-MS Bioanalysis: Best Practices, Experimental Protocols, and Regulations. Jhon Wiley. Canada; 2013. 704 p. Available from: https://books.google.com.co/books?id=yYOuAAAAQBAJ&printsec=frontcover&dq=LC-MS&hl=es&sa=X&redir_esc=y#v=onepage&q=LC-MS&f=falseBarnes S, Benton HP, Casazza K, Cooper SJ, Cui X, Du X, et al. Training in metabolomics research. I. Designing the experiment, collecting and extracting samples and generating metabolomics data. J Mass Spectrom. 2016 Jul 1;51(7):461. Available from: /pmc/articles/PMC4964969/Dunn WB, Wilson ID, Nicholls AW, Broadhurst D. The importance of experimental design and QC samples in large-scale and MS-driven untargeted metabolomic studies of humans. Bioanalysis. 2012 Sep;4(18):2249–64. Available from: https://pubmed.ncbi.nlm.nih.gov/23046267/Lee AY, Troisi J, Symes SJK. Experimental design in metabolomics. Metabolomics Perspect. 2022 Jan 1;27–61.EMBL-EBI. Designing a metabolomics study. Available from: https://www.ebi.ac.uk/training/online/courses/metabolomics-introduction/designing-a-metabolomics-study/Jacyna J, Kordalewska M, Markuszewski MJ. Design of Experiments in metabolomics-related studies: An overview. J Pharm Biomed Anal. 2019 Feb 5;164:598–606.Méndez Rodríguez KB, Santoyo Treviño MJ, Saldaña Villanueva K, Rodríguez Aguilar M, Flores Ramírez R, Pérez Vázquez FJ. Metabolomics as a new tool for timely diagnosis in noncommunicable diseases. Rev salud Ambient. 2019;19(2):109–15.Libiseller G, Dvorzak M, Kleb U, Gander E, Eisenberg T, Madeo F, et al. IPO: a tool for automated optimization of XCMS parameters. BMC Bioinformatics. 2015 Apr 16;16(1). Available from: /pmc/articles/PMC4404568/Andaluz sociedad grupo regional analítica E de química. BOLETÍN GRASEQA Metabolómica. García Reyes JF, editor. 2012;56.Naz S, Moreira Dos Santos DC, García A, Barbas C. Analytical protocols based on LC-MS, GC-MS and CE-MS for nontargeted metabolomics of biological tissues. Bioanalysis. 2014;6(12):1657–77. Available from: https://pubmed.ncbi.nlm.nih.gov/25077626/Mastrangelo A, Ferrarini A, Rey-Stolle F, García A, Barbas C. From sample treatment to biomarker discovery: A tutorial for untargeted metabolomics based on GC-(EI)-Q-MS. Anal Chim Acta. 2015 Nov 5;900:21–35.Jiye A, Trygg J, Gullberg J, Johansson AI, Jonsson P, Antti H, et al. Extraction and GC/MS analysis of the human blood plasma metabolome. Anal Chem. 2005 Dec 15;77(24):8086–94. Available from: https://pubmed.ncbi.nlm.nih.gov/16351159/Garcia A, Barbas C. Gas chromatography-mass spectrometry (GC-MS)-based metabolomics. Methods Mol Biol. 2011;708:191–204. Available from: https://pubmed.ncbi.nlm.nih.gov/21207291/Nishikaze T. Sialic acid derivatization for glycan analysis by mass spectrometry. Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(9):523. Available from: /pmc/articles/PMC6856002/David V, Moldoveanu SC, Galaon T. Derivatization procedures and their analytical performances for HPLC determination in bioanalysis. Biomed Chromatogr. 2021 Jan 1;35(1):e5008. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/bmc.5008Akula RK, Kwon YU. Bioenzymatic and Chemical Derivatization of Renewable Fatty Acids. Biomolecules. 2019 Oct 1;9(10). Available from: /pmc/articles/PMC6843907/Marshall DD, Powers R. Beyond the Paradigm: Combining Mass Spectrometry and Nuclear Magnetic Resonance for Metabolomics. Prog Nucl Magn Reson Spectrosc. 2017 May 1;100:1. Available from: /pmc/articles/PMC5448308/Perez HL, Evans CA. Chemical derivatization in bioanalysis. http://dx.doi.org/104155/bio15182. 2015 Nov 3;7(19):2435–7. Available from: https://www.future-science.com/doi/full/10.4155/bio.15.182Domingues P, García A, Skrzydlewska E. Advanced Analytical Chemistry for Life Sciences. Bialystok: Liberlibro.com A.C.; Available from: https://www.umb.edu.pl/photo/pliki/projekty_umb/aac/aaclifesci-manual-spanish_with-cover.pdfWu D, Shu T, Yang X, Song J-X, Zhang M, Yao C, et al. Plasma metabolomic and lipidomic alterations associated with COVID-19. Natl Sci Rev. 2020 Jul 1;7(7):1157–68. Available from: https://academic.oup.com/nsr/article/7/7/1157/5826189Zheng F, Lin Y, Boulas P. Development and validation of a novel HILIC method for the quantification of low-levels of cuprizone in cuprizone-containing chow. Sci Reports 2021 111. 2021 Sep 9;11(1):1–10. Available from: https://www.nature.com/articles/s41598-021-97590-zUnsihuay D, Mesa Sanchez D, Laskin J. Quantitative Mass Spectrometry Imaging of Biological Systems. Annu Rev Phys Chem. 2021 Apr 20;72:307. Available from: /pmc/articles/PMC8161172/Bantscheff M, Schirle M, Sweetman G, Rick J, Kuster B. Quantitative mass spectrometry in proteomics: a critical review. Anal Bioanal Chem 2007 3894. 2007 Aug 1;389(4):1017–31. Available from: https://link.springer.com/article/10.1007/s00216-007-1486-6Han X, Aslanian A, Yates JR. Mass Spectrometry for Proteomics. Curr Opin Chem Biol. 2008 Oct ;12(5):483. Available from: /pmc/articles/PMC2642903/Nauta SP, Poeze M, Heeren RMA, Porta Siegel T. Clinical use of mass spectrometry (imaging) for hard tissue analysis in abnormal fracture healing. Clin Chem Lab Med. 2020 Jun 1;58(6):897–913. Available from: https://www.degruyter.com/document/doi/10.1515/cclm-2019-0857/htmlBuchberger AR, DeLaney K, Johnson J, Li L. Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights. Anal Chem. 2018 Jan 2;90(1):240. Available from: /pmc/articles/PMC5959842/Indelicato S, Bongiorno D, Ceraulo L. Recent Approaches for Chemical Speciation and Analysis by Electrospray Ionization (ESI) Mass Spectrometry. Front Chem. 2020 Jan 20;8:625945. Available from: /pmc/articles/PMC7855954/Ryan DJ, Spraggins JM, Caprioli RM. Protein Identification Strategies in MALDI Imaging Mass Spectrometry: A Brief Review. Curr Opin Chem Biol. 2019 Feb 1;48:64. Available from: /pmc/articles/PMC6382520/Milewska A, Ner-Kluza J, Dabrowska A, Bodzon-Kulakowska A, Pyrc K, Suder P. MASS SPECTROMETRY IN VIROLOGICAL SCIENCES. Mass Spectrom Rev. 2020 Sep 1;39(5–6):499–522. Available from: /pmc/articles/PMC7228374/Pitt JJ. Principles and Applications of Liquid Chromatography-Mass Spectrometry in Clinical Biochemistry. Clin Biochem Rev. 2009 Feb;30(1):19. Available from: /pmc/articles/PMC2643089/Fang Z, Gonzalez FJ. LC–MS‑based metabolomics: an update. Arch Toxicol. 2014;88(8):1491. Available from: /pmc/articles/PMC6310611/Fiehn O. Metabolomics by Gas Chromatography-Mass Spectrometry: the combination of targeted and untargeted profiling. Curr Protoc Mol Biol. 2016 Apr 1;114:30.4.1. Available from: /pmc/articles/PMC4829120/KK Pasikanti, PC Ho, EC Chan. Gas chromatography/mass spectrometry in metabolic profiling of biological fluids. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Aug 15;871(2):202–11. Available from: https://pubmed.ncbi.nlm.nih.gov/18479983/UNLP F de CA y F-. INTRODUCCIÓN A LAS SEPARCIONES ANALÍTICAS. Available from: https://aulavirtual.agro.unlp.edu.ar/pluginfile.php/35288/mod_resource/content/1/2 cromatografia 2017.pdfJW H. Gas chromatography-mass spectrometry. Methods Mol Biol. 2006;324:53–74. Available from: https://pubmed.ncbi.nlm.nih.gov/16761371/Gomis Yagües V. Tema 4. Cromatografía de líquidos de alta resolución. 2008. Available from: http://hdl.handle.net/10045/8248Buszewski B, Noga S. Hydrophilic interaction liquid chromatography (HILIC)—a powerful separation technique. Anal Bioanal Chem. 2012 Jan;402(1):231. Available from: /pmc/articles/PMC3249561/Boersema PJ, Mohammed S, Heck AJR. Hydrophilic interaction liquid chromatography (HILIC) in proteomics. Anal Bioanal Chem. 2008 May 9;391(1):151–9. Available from: https://link.springer.com/article/10.1007/s00216-008-1865-7Paczkowska M, Mizera M, Tężyk A, Zalewski P, Dzitko J, Cielecka-Piontek J. Hydrophilic interaction chromatography (HILIC) for the determination of cetirizine dihydrochloride. Arab J Chem. 2019 Dec 1;12(8):4204–11.Harvey KA, Walker CL, Xu Z, Whitley P, Pavlina TM, Hise M, et al. Oleic acid inhibits stearic acid-induced inhibition of cell growth and pro-inflammatory responses in human aortic endothelial cells. J Lipid Res. 2010 Dec;51(12):3470. Available from: /pmc/articles/PMC2975719/Stubbs BJ, Koutnik AP, Goldberg EL, Upadhyay V, Turnbaugh PJ, Verdin E, et al. Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections. Med (New York, N.y). 2020 Dec 12;1(1):43. Available from: /pmc/articles/PMC7362813/Fahy E, Subramaniam S, Alex Brown H, Glass CK, Merrill AH, Murphy RC, et al. A comprehensive classification system for lipids1. J Lipid Res. 2005 May 1;46(5):839–61. Available from: http://www.jlr.org/article/S0022227520339687/fulltextGomez-Gomez A, Rodríguez-Morató J, Haro N, Marín-Corral J, Masclans JR, Pozo OJ. Untargeted detection of the carbonyl metabolome by chemical derivatization and liquid chromatography-tandem mass spectrometry in precursor ion scan mode: Elucidation of COVID-19 severity biomarkers. Anal Chim Acta. 2022 Mar 1;1196. Available from: https://pubmed.ncbi.nlm.nih.gov/35151400/Shi D, Yan R, Lv L, Jiang H, Lu Y, Sheng J, et al. The serum metabolome of COVID-19 patients is distinctive and predictive. Metabolism. 2021 May 1;118:154739. Available from: /pmc/articles/PMC7920809/Landaas S, Jakobs C. The occurrence of 2-hydroxyisovaleric acid in patients with lactic acidosis and ketoacidosis. Clin Chim Acta. 1977 Aug 1;78(3):489–93. Available from: https://pubmed.ncbi.nlm.nih.gov/884872/Patel U, Deluxe L, Salama C, Jimenez AR, Whiting A, Lubin C, et al. Evaluation of Characteristics and Outcomes for Patients with Diabetic Ketoacidosis (DKA) With and Without COVID-19 in Elmhurst Queens During Similar Three-Month Periods in 2019 and 2020. Cureus. 2021 Jul 16;13(7). Available from: /pmc/articles/PMC8364784/Gupta GS. The Lactate and the Lactate Dehydrogenase in Inflammatory Diseases and Major Risk Factors in COVID-19 Patients. Inflammation. 2022 Dec 1;45(6):2091. Available from: /pmc/articles/PMC9117991/Stromberg S, Baxter BA, Dooley G, LaVergne SM, Gallichotte E, Dutt T, et al. Relationships between plasma fatty acids in adults with mild, moderate, or severe COVID-19 and the development of post-acute sequelae. Front Nutr. 2022 Sep 14;9. Available from: /pmc/articles/PMC9515579/Leonard J V. Recent advances in amino acid and organic acid metabolism. J Inherit Metab Dis. 2007 Apr;30(2):134–8. Available from: https://pubmed.ncbi.nlm.nih.gov/17237988/Papagianni M. Organic Acids. Compr Biotechnol Second Ed. 2011 Jan 1;1:109–20.Rees CA, Rostad CA, Mantus G, Anderson EJ, Chahroudi A, Jaggi P, et al. Brief Report: Altered amino acid profile in patients with SARS-CoV-2 infection. Proc Natl Acad Sci U S A. 2021 Jun 6;118(25). Available from: /pmc/articles/PMC8237604/Atila A, Alay H, Yaman ME, Akman TC, Cadirci E, Bayrak B, et al. The serum amino acid profile in COVID-19. Amino Acids. 2021 Oct 1;53(10):1569. Available from: /pmc/articles/PMC8487804/Páez-Franco JC, Maravillas-Montero JL, Mejía-Domínguez NR, Torres-Ruiz J, Tamez-Torres KM, Pérez-Fragoso A, et al. Metabolomics analysis identifies glutamic acid and cystine imbalances in COVID-19 patients without comorbid conditions. Implications on redox homeostasis and COVID-19 pathophysiology. PLoS One. 2022 Sep 1;17(9). Available from: /pmc/articles/PMC9488784/Kalyanaraman B. Reactive oxygen species, proinflammatory and immunosuppressive mediators induced in COVID-19: overlapping biology with cancer. RSC Chem Biol. 2021 Oct 10;2(5):1402. Available from: /pmc/articles/PMC8496060/Laforge M, Elbim C, Frère C, Hémadi M, Massaad C, Nuss P, et al. Tissue damage from neutrophil-induced oxidative stress in COVID-19. Nat Rev Immunol. 2020 Sep 1;20(9):515. Available from: /pmc/articles/PMC7388427/Kim HY, Lee H, Kim SH, Jin H, Bae J, Choi HK. Discovery of potential biomarkers in human melanoma cells with different metastatic potential by metabolic and lipidomic profiling. Sci Rep. 2017 Dec 1;7(1). Available from: /pmc/articles/PMC5562697/Bharadwaj S, Singh M, Kirtipal N, Kang SG. SARS-CoV-2 and Glutamine: SARS-CoV-2 Triggered Pathogenesis via Metabolic Reprograming of Glutamine in Host Cells. Front Mol Biosci. 2021 Jan 11;7:462.Lieber C. Pathogenesis and treatment of alcoholic liver disease: progress over the last 50 years - PubMed. Rocz Akad Med Bialymst. 2005;50:7–20. Available from: https://pubmed.ncbi.nlm.nih.gov/16363067/McMenamy RH, Vang J, Drapanas T. Amino acid and alpha-keto acid concentrations in plasma and blood of the liverless dog. Am J Physiol. 1965;209(5):1046–52. Available from: https://pubmed.ncbi.nlm.nih.gov/5849485/Yudkoff M, Blazer-Yost B, Cohn R, Segal S. On the clinical significance of the plasma alpha-amino-n-butyric acid:leucine ratio. Am J Clin Nutr. 1979;32(2):282–5. Available from: https://pubmed.ncbi.nlm.nih.gov/420125/Darling PB, Grunow J, Rafii M, Brookes S, Ball RO, Pencharz PB. Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans. Am J Physiol Endocrinol Metab. 2000;278(5). Available from: https://pubmed.ncbi.nlm.nih.gov/10780944/Fonteh AN, Harrington RJ, Tsai A, Liao P, Harrington MG. Free amino acid and dipeptide changes in the body fluids from Alzheimer’s disease subjects. Amino Acids. 2007 Feb;32(2):213–24. Available from: https://pubmed.ncbi.nlm.nih.gov/17031479/Yang J, Chen T, Sun L, Zhao Z, Qi X, Zhou K, et al. Potential metabolite markers of schizophrenia. Mol Psychiatry. 2013 Jan;18(1):67. Available from: /pmc/articles/PMC3526727/Ni Y, Xie G, Jia W. Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery. J Proteome Res. 2014 Sep 5;13(9):3857–70. Available from: https://pubmed.ncbi.nlm.nih.gov/25105552/Cheng Y, Xie G, Chen T, Qiu Y, Zou X, Zheng M, et al. Distinct urinary metabolic profile of human colorectal cancer. J Proteome Res. 2012 Feb 3;11(2):1354–63. Available from: https://pubmed.ncbi.nlm.nih.gov/22148915/Woo HI, Chun MR, Yang JS, Lim SW, Kim MJ, Kim SW, et al. Plasma Amino Acid Profiling in Major Depressive Disorder Treated With Selective Serotonin Reuptake Inhibitors. CNS Neurosci Ther. 2015 May 1;21(5):417. Available from: /pmc/articles/PMC6495833/Adachi Y, Toyoshima K, Nishimoto R, Ueno S, Tanaka T, Imaizumi A, et al. Association between plasma α-aminobutyric acid and depressive symptoms in older community-dwelling adults in Japan. Geriatr Gerontol Int. 2019 Mar 1;19(3):254–8. Available from: https://pubmed.ncbi.nlm.nih.gov/30561103/Chiarla C, Giovannini I, Siegel JH. Characterization of alpha-amino-n-butyric acid correlations in sepsis. Transl Res. 2011;158(6):328–33. Available from: https://pubmed.ncbi.nlm.nih.gov/22061040/Lee YK, Chang WC, Prakash E, Peng YJ, Tu Z, Lin CH, et al. Carbohydrate Ligands for COVID-19 Spike Proteins. Viruses. 2022 Feb 1;14(2). Available from: /pmc/articles/PMC8880561/Del-Corso A, Cappiello M, Moschini R, Balestri F, Mura U, Ipata PL. The furanosidic scaffold of d-ribose: a milestone for cell life. Biochem Soc Trans. 2019 Dec 20;47(6):1931–40. Available from: /biochemsoctrans/article/47/6/1931/221031/The-furanosidic-scaffold-of-d-ribose-a-milestoneAlhammad YMO, Kashipathy MM, Roy A, Gagné J-P, McDonald P, Gao P, et al. The SARS-CoV-2 Conserved Macrodomain Is a Mono-ADP-Ribosylhydrolase. J Virol. 2021 Jan 13;95(3). Available from: /pmc/articles/PMC7925111/Frick DN, Virdi RS, Vuksanovic N, Dahal N, Silvaggi NR. Molecular Basis for ADP-Ribose Binding to the Mac1 Domain of SARS-CoV-2 nsp3. Biochemistry. 2020 Jul 21;59(28):2608–15. Available from: /pmc/articles/PMC7341687/Li Y, Zhang D, Gao X, Wang X, Zhang L. 2′- and 3′-Ribose Modifications of Nucleotide Analogues Establish the Structural Basis to Inhibit the Viral Replication of SARS-CoV-2. J Phys Chem Lett. 2022;4111–8.Noguchi C, Kamitori K, Hossain A, Hoshikawa H, Katagi A, Dong Y, et al. D-Allose Inhibits Cancer Cell Growth by Reducing GLUT1 Expression. Tohoku J Exp Med. 2016 Jan 30;238(2):131–41.Gao D, Kawai N, Nakamura T, Lu F, Fei Z, Tamiya T. Anti-inflammatory Effect of D-Allose in Cerebral Ischemia/Reperfusion Injury in Rats. Neurol Med Chir (Tokyo). 2013;53(6):365–74.Lv L, Jiang H, Chen Y, Gu S, Xia J, Zhang H, et al. The faecal metabolome in COVID-19 patients is altered and associated with clinical features and gut microbes. Anal Chim Acta. 2021 Apr 1;1152:338267. Available from: /pmc/articles/PMC7847702/Zhao J, Zhang G, Zhang Y, Yi D, Li Q, Ma L, et al. 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides: SARS-CoV-2 RNA-dependent RNA polymerase inhibitors. Antiviral Res. 2021 Dec 1;196:105209. Available from: /pmc/articles/PMC8600920/Matchett WH. Inhibition of Tryptophan Synthetase by Indoleacrylic Acid. J Bacteriol. 1972 Apr;110(1):146. Available from: /pmc/articles/PMC247391/?report=abstractWlodarska M, Luo C, Kolde R, d’Hennezel E, Annand JW, Heim CE, et al. Indoleacrylic acid produced by commensal Peptostreptococcus species suppresses inflammation. Cell Host Microbe. 2017 Jul 7;22(1):25. Available from: /pmc/articles/PMC5672633/Espadinha M, Barcherini V, Gonçalves LM, Molins E, Antunes AMM, Santos MMM. Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma. Pharmaceuticals. 2021 Mar 1;14(3):208. Available from: /pmc/articles/PMC8001353/Fawazy NG, Panda SS, Mostafa A, Kariuki BM, Bekheit MS, Moatasim Y, et al. Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties. Sci Rep. 2022 Dec 1;12(1):13880. Available from: /pmc/articles/PMC9380671/Jochum M, Lee MD, Curry K, Zaksas V, Vitalis E, Treangen T, et al. Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease. Sci Rep. 2022 Dec 1;12(1). Available from: /pmc/articles/PMC9729217/Chowdhury P, Pathak P. Neuroprotective immunity by essential nutrient “Choline” for the prevention of SARS CoV2 infections: An in silico study by molecular dynamics approach. Chem Phys Lett. 2020 Dec 12;761:138057. Available from: /pmc/articles/PMC7532804/Orfei MD, Porcari DE, D’Arcangelo S, Maggi F, Russignaga D, Ricciardi E. A New Look on Long-COVID Effects: The Functional Brain Fog Syndrome. J Clin Med. 2022 Oct 1;11(19). Available from: /pmc/articles/PMC9573330/Al-kuraishy HM, Al-Buhadily AK, Al-Gareeb AI, Alorabi M, Hadi Al-Harcan NA, El-Bouseary MM, et al. Citicoline and COVID-19: vis-à-vis conjectured. Naunyn-Schmiedeberg’s Arch Pharmacol 2022 39512. 2022 Sep 5;395(12):1463–75. Available from: https://link.springer.com/article/10.1007/s00210-022-02284-6Feher J. Pancreatic and Biliary Secretion. Quant Hum Physiol. 2012 Jan 1;721–30.Thuy PX, Bao TDD, Moon EY. Ursodeoxycholic acid ameliorates cell migration retarded by the SARS-CoV-2 spike protein in BEAS-2B human bronchial epithelial cells. Biomed Pharmacother. 2022 Jun 1;150:113021. Available from: /pmc/articles/PMC9035373/Estudio de factores pronósticos de ingreso a unidad de Cuidado Intensivo y mortalidad a través de perfiles metabolómicos en sujetos positivos para SARS-CoV-2 en una población bogotanaDirección de investigación y extensión, Universidad Nacional de ColombiaLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/84652/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL1013648404.2022.pdf1013648404.2022.pdfTesis de Maestría en Ciencias - Bioquímicaapplication/pdf4877511https://repositorio.unal.edu.co/bitstream/unal/84652/2/1013648404.2022.pdfeafd05bcbb1da8e2b7060fc3bb935a71MD52THUMBNAIL1013648404.2022.pdf.jpg1013648404.2022.pdf.jpgGenerated Thumbnailimage/jpeg6144https://repositorio.unal.edu.co/bitstream/unal/84652/3/1013648404.2022.pdf.jpg81fb9d98eff18e0acb9853f912ebafeaMD53unal/84652oai:repositorio.unal.edu.co:unal/846522024-08-18 23:13:05.732Repositorio Institucional Universidad Nacional de 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