Potencial uso terapéutico del ARN de interferencia contra la COVID-19

Dany A. Cuello-Almarales, Luis Enrique Almaguer Mederos, Dennis Almaguer-Gotay

Texto completo:

XML PDF

Resumen

Introducción: El SARS-CoV-2 es el agente causal de la COVID-19, enfermedad respiratoria que ha causado miles de víctimas fatales a escala global, y para la cual no existe ninguna terapia curativa efectiva.

Objetivo: Reflejar la relevancia potencial de la tecnología de ARN de interferencia (ARNi), como alternativa terapéutica contra la COVID-19.

Material y métodos: Se consultaron las bases de datos especializadas en busca de artículos publicados hasta abril de 2020. Se emplearon descriptores específicos y operadores booleanos. Se empleó la estrategia de búsqueda avanzada para la selección de los artículos, teniendo en cuenta la calidad metodológica o validez de los estudios.

Desarrollo: Fueron identificadas evidencias de aplicación a nivel experimental de la tecnología de ARNi contra el SARS-CoV. Se han diseñado y evaluado varios ARNs pequeños interferentes y ARNs pequeños con estructura en lazo, orientados al silenciamiento de genes esenciales del SARS-CoV, incluyendo aquellos que codifican las proteínas S, RdRp, M, E, N, 3a/3b y 7a/7b. Se comprobó la efectividad de los ARNi en el silenciamiento de sus genes diana. Aunque la mayoría de estas investigaciones se han realizado en sistemas in vitro, también se ha comprobado la utilidad terapéutica de la administración intranasal de ARNi en un modelo de SARS-CoV in vivo.

Conclusiones: La tecnología de ARNi ha mostrado potencialidades como estrategia terapéutica contra el SARS-CoV en modelos celulares y animales. Dadas las similitudes a nivel genómico y en cuanto al proceso patogénico entre SARS-CoV y SARS-CoV-2, esta tecnología es potencialmente aplicable el tratamiento de la COVID-19.

Palabras clave

COVID-19, SARS-CoV, SARS-CoV-2, ARN de interferencia, terapia antiviral.

Referencias

Guarner J. Three emerging coronaviruses in two decades: the story of SARS, MERS, and now COVID-19. Am J Clin Pathol. 2020; 153(4):1-2.

Xiaowei L, Manman G, Yizhao P, Liesu M, Shemin L. Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis [Internet]. 2020 [Citado 26/03/2020];10:[Aprox. 2p.]. Disponible en: https://doi.org/10.1016/j.jpha.2020.03.001

Hussin A. Rothana, Siddappa N. Byrareddy. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of Autoimmunity [Internet]. 2020 [Citado 26/03/2020];109:[Aprox. 2p.]. Disponible en: https://doi.org/10.1016/j.jaut.2020.102433

Zhe X, Lei S, Yijin W, Jiyuan Z, Lei H, Chao Z, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Resp Med [Internet]. 2020 [Citado 26/03/2020];8:[Aprox. 2p.]. Disponible en: https://doi.org/10.1016/S2213-2600(20)30076-X

Hui DS, Azha EI, Kim YJ, Memish ZA, Myoungdon Oh, Zumla A. Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis. 2018; 18: 217-27.

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270-3.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395 (10224):565-74.

Pietro HG, Daniele M, Carmine C, Federico MG. Master regulator analysis of the SARS-CoV-2/Human interactome. J Clin Med [Internet]. 2020 [Citado 26/03/2020];9:[Aprox. 2p.]. Disponible en: https://doi.org/10.3390/jcm9040982

Zhu N, Dingyu Z, Wenling W, Xingwang L, Bo Y, Jingdong S, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020; 382:727-33.

Lai CC, Liu YH, Wang CY, Wang YH, Hsueh SC, Yen MY, et al. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS -CoV-2): Facts and myths. J Microbiol Immunol Infect [Internet]. 2020 [Citado 26/03/2020];53:[Aprox. 2p.]. Disponible en: https://doi.org/10.1016/j.jmii.2020.02.012

The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Vital Surveillances: The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19). China CDC Wkly [Internet]. 2020 [Citado 26/03/2020];2:[Aprox. 2p.]. Disponible en: http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51

Zhang XN, Xiong W, Wang JD, Hu YW, Xiang L, Yuan ZH. siRNA-mediated inhibition of HBV replication and expression. World J Gastroenterol. 2004; 10(20):2967-71.

Ashfaq UA, Yousaf MZ, Aslam M, Ejaz R, Jahan S, Ullah O. siRNAs: Potential therapeutic agents against Hepatitis C Virus. Virol J. 2011; 8:276.

Qin XF, An DS, Chen IS, Baltimore D. Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci USA. 2003; 100:183-8.

Chang JW, Yi Lin C. Antiviral applications of RNAi for coronavirus. Expert Opin Investig Drugs. 2006;15(2):89-97.

Zhang Y, Li T, Fu L, Yu C, Li Y, Xu X, et al. Silencing SARS-CoV spike protein expression in cultured cells by RNA interference. FEBS Lett. 2004; 560:141-6.

Wu CJ, Huang HW, Liu CY, Hong CF, Chan YL. Inhibition of SARS-CoV replication by siRNA. Antiviral Res. 2005; 65(1):45-8.

Kurreck J. RNA interference: from basic research to therapeutic applications. Angew Chem Int Ed Engl. 2009; 48(8):1378-98.

Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020; 579(7798):265-9.

World health Organization. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) [Internet]. Geneva: World Health Organization; 2020 [Citado 26/03/2020]. Disponible en: https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf

Lai M, Holmes KV. Coronaviridae: the viruses and their replication. In: Knipe D, Howley P. Fields’ Virology. Philadelphia: Lippincott Williams & Wilkins; 2001.p. 1163-85.

Adnan Y, Muhammad IS, Chang KK, Ki Byung L. RNA Interference (RNAi) Induced Gene Silencing: A Promising Approach of Hi-Tech Plant Breeding. Int J Biol Sci. 2014; 10(10): 1150-8.

Davidson BL, McCray PB Jr. Current prospects for RNA interference-based therapies. Nat Rev Genet. 2011; 12(5):329-40.

Saxena S, Jónsson ZO, Dutta A. Small RNAs with imperfect match to endogenous mRNA repress translation. Implications for off-target activity of small inhibitory RNA in mammalian cells. J Biol Chem. 2003; 278(45):44312-9.

Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci. 2003; 100(17):9779-84.

Clemens MJ, Elia A. The double-stranded RNA-dependent protein kinase PKR: structure and function. J. Interferon & Cytokine Res. 1997; 17:503-24.

Elbashir S M, Lendeckel W, Tuschl T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 2001; 15(2):188-200.

Chen SY, Shiau AL, Li YT, Lin YS, Lee CH, Wu CL, et al. Suppression of collagen-induced arthritis by intra-articular lentiviral vector-mediated delivery of Toll-like receptor 7 short hairpin RNA gene. Gene Ther. 2012; 19(7):752-60.

Pushparaj PN, Aarthi JJ, Manikandan J, Kumar SD. siRNA. miRNA, and shRNA: in vivo applications. J Dent Res. 2008; 87(11):992-1003.

Taxman DJ, Livingstone LR, Zhang J, Conti BJ, Locca HA, Williams KL, et al. Criteria for effective design, construction, and gene knockdown by shRNA vectors. BMC Biotechnol [Internet]. 2006 [Citado 26/03/2020];6:[Aprox. 2p.]. Disponible en: https://doi.org/10.1186/1472-6750-6-7

Linda BC, Katherine AH. Viral vector-mediated RNA interference. Curr Opin Pharmacol. 2010; 10(5):534-42.

Jacque JM, Triques K, Stevenson M. Modulation of HIV-1 replication by RNA interference. Nature. 2002; 418(6896):435-8.

Stephen JB, Fawzi FB, Nigel AJ, Millan M. RNA interference for viral infections. Current Drug Targets. 2012; 13(11):1411-20.

Belasio EF, Raimondo M, Suligoi B, Buttò S. HIV virology and pathogenetic mechanisms of infection: a brief overview. Ann Ist Super Sanita. 2010; 46(1):5-14.

Novina CD, Murray MF, Dykxhoorn DM, Beresford PJ, Riess J, Lee SK, et al. siRNA-directed inhibition of HIV-1 infection. Nat Med 2002; 8(7): 681-6.

Das AT, Brummelkamp TR, Westerhout EM, Vink M, Madiredjo M, Bernards R, et al. Human Immunodeficiency Virus Type 1 escapes from RNA interference-mediated inhibition. J Virol. 2004; 78(5): 2601-5.

Surabhi RM, Gaynor RB. RNA Interference directed against viral and cellular targets inhibits Human Immunodeficiency Virus Type 1 replication. J Virol. 2002; 76(24):12963-73.

Catarina CS, Pedro RL, Francisco M, Joana GO, Miguel C, Ana M, et al. Inhibition of HIV replication through siRNA carried by CXCR4 targeted chimeric nanobody. Cellular and Molecular Life Sciences [Internet]. 2019 [Citado 26/03/2020];75:[Aprox. 2p.]. Disponible en: https://doi.org/10.1007/s0001 8-019-03334 -8

Lee NS, Dohjima T, Bauer G, Li H, Li MJ, Ehsani A, et al. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat Biotechnol. 2002; 20:500-5.

Alesia L, Minna MP. RNA interference as a prospective tool for the control of human viral infections. Front Microbiol [Internet]. 2018 [Citado 26/03/2020];9:[Aprox. 2p.]. Disponible en: https://doi.org/10.3389/fmicb.2018.02151

Flisiak R, Jaroszewicz, Lucejko M. siRNA drug development against hepatitis B virus infection. Expert Opin Biol Ther. 2018; 18(6):609-17.

Bitko V, Barik S. Phenotypic silencing of cytoplasmic genes using sequence-specific double-stranded short interfering RNA and its application in the reverse genetics of wild type negative-strand RNA viruses. BMC Microbiol. 2001; 1:34.

Fujii T, Nakamura T, Iwamoto A. Current concepts in SARS treatment. J Infect Chemother. 2004; 10(1):1-7.

Palacios MC, Santos E, Velázquez C, León MJ. COVID-19, una emergencia de salud pública mundial. Rev Clin Esp [Internet]. 2020 [Citado 26/03/2020];220:[Aprox. 2p.]. Disponible en: https://doi.org/10.1016/j.rce.2020.03.001

Pang J, Wang MX, Ang IYH, Tan SHX, Lewis RF, Chen JI P, et al. Potential rapid diagnostics, vaccine and therapeutics for 2019 Novel Coronavirus (2019-nCoV): A systematic review. J Clin Med. 2020; 9(3):623.

Hoffmann M, Kleine Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020; 16;181(2):271-80.

Xu J, Zhao S, Teng T, Abualgasim EA, Zhu W, Xie L, et al. Systematic comparison of two animal-to-human transmitted human coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses [Internet]. 2020 [Citado 26/03/2020];22(2):244. Disponible en: https:// doi.org/10.3390/v12020244

Vennema H, Heijnen L, Zijderveld A, Horzinek MC, Spaan WJ. Intracellular transport of recombinant coronavirus spike proteins: implications for virus assembly. J Virol. 1990; 64(1):339-46.

Ming LH, Bojian Z, Ying P, Joseph SM, Leo LM, Kwok Y, et al. Inhibition of SARS-associated coronavirus infection and replication by RNA interference. JAMA. 2003; 290:2665-6.

Thiel V, Herold J, Schelle B, Siddell SG. Viral replicase gene products suffice for coronavirus discontinuous transcription. J Virol. 2001; 75(14):6676-81.

Thiel V, Ivanov KA, Putics Á, Hertzig T, Schelle B, Bayer S, et al. Mechanisms and enzymes involved in SARS coronavirus genome expression. J Gen Virol. 2003; 84(9):2305-15.

Zhi W, Ren L, Zhao X, Hung T, Meng A, Wang J, et al. Inhibition of Severe Acute Respiratory Syndrome Virus Replication by Small Interfering RNAs in Mammalian Cells. J Virol. 2004; 78(14): 7523-7.

Xue Z, Kailang W, Xin Y, Ying Z, Jianguo W. Inhibition of SARS-CoV gene expression by adenovirus-delivered small hairpin RNA. Intervirology. 2007; 50(2):63-70.

Ying W, Ying Li C, Fan Y, Yun Z, Shu Hui W, Li L. Small interfering RNA Effectively inhibits the expression of SARS coronavirus membrane gene at two novel targeting sites. Molecules. 2010; 15(10): 7197-207.

Fang X, Gao J, Zheng H, Li B, Kong L, Zhang Y, et al. The membrane protein of SARS-CoV suppresses NF-kappaB activation. J Med Virol. 2007; 79:1431-9.

Siu KL, Kok KH, Nog MH, Poon VK, Yuen KY, Zheng BJ, et al. Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex. J Biol Chem. 2009; 284(24):16202-9.

Akerström S, Mirazimi A, Tan YJ. Inhibition of SARS-CoV replication cycle by small interference RNAs silencing specific SARS proteins, 7a/7b, 3a/3b and S. Antiviral Res. 2007; 73(3):219-27.

Li BJ, Tang Q, Cheng D, Qin C, Xie FY, Wei Q, et al. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in rhesus macaque. Nat Med. 2005; 11(9):944-51.

Almaguer LE, Cuello DA, Almaguer D. Rol de los genes ACE2 y TMPRSS2 en la susceptibilidad/gravedad a la COVID-19. Anal Acad Cienc Cuba [Internet]. 2020 [Citado 26/03/2020];10(2):[Aprox. 2p.]. Disponible en:

http://www.revistaccuba.sld.cu/index.php/revacc/article/view/799

Comentarios sobre este artículo

Ver todos los comentarios
 |  Añadir comentario

Licencia de Creative Commons
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.