A propósito de un caso: uso de la silimarina/silibinina como análogo molecular del remdesivir para el tratamiento de pacientes diagnosticados de COVID-19 con síndrome de dificultad respiratoria aguda leve o moderado. Reporte de caso

Mauro Antonio  Falconi García; Juan Esteban  Guevara Betancur

doi:10.54495/Rev.Cientifica.v30i2.286

Autores/as

Mauro Antonio Falconi García Centro de Atención ambulatorio El Batán IESS, Quito, Ecuador,
Juan Esteban Guevara Betancur Centro de Atención ambulatorio El Batán IESS, Quito, Ecuador,

DOI:

https://doi.org/10.54495/Rev.Cientifica.v30i2.286

Palabras clave:

SARS-COV2, COVID 19, Tratamiento opcional.

Resumen

La enfermedad respiratoria causada por el SARS-CoV2 es una enfermedad de origen viral infectocontagiosa que afecta a nuestra población en especial adultos mayores y adultos jóvenes en todo el mundo. Una de las principales causas de esta patología es la limitada capacidad de inmunización a nivel global en especial en países en desarrollo para combatir los brotes de esta enfermedad. Se desarrolla en fases de sintomatología respiratoria muy característica lo cual puede orientar para un diagnóstico temprano, de lo contrario puede requerir hospitalización para tratamiento; a nivel mundial y local se han intentado diferentes terapéuticas sin éxito completo. El diagnóstico presuntivo es clínico y el confirmatorio por medio de hisopados nasofaríngeos, que aíslan virus beta, coronavirus SARS–CoV-2, nombre emitido por la Organización Mundial de la Salud, quien declaró la pandemia para esta enfermedad en particular. Se presenta un caso de paciente con la enfermedad producida por el virus en mención que acude a nuestra casa de salud, por no acceder a una unidad hospitalaria de mayor complejidad, por la saturación hospitalaria, con un síndrome respiratorio leve a moderado, en vista de la imposibilidad de acceder a otros tratamientos iniciamos la administración de silimarina/silibinina en dosis diarias dos veces por dia. Con el fin de que el tratamiento probado con diferentes moléculas sea común denominador del mismo que se basa en el atacar la cascada de citocinas inflamatorias derivadas por la activación del receptor STAT3 y la modulación del IFG tipo 1; con corticoterapia principalmente dexametasona, o metilprednisolona, y moléculas como Remdesivir, Sofosbuvir y Ribavirin, las cuales continúan en foco de discusión por lo que se evalúan tratamientos opcionales para combatir los efectos de esta enfermedad. La incidencia de esta enfermedad es global, mostrándose más alta en países subdesarrollados los cuales no cuentan con un apropiado programa de inmunización.

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Citas

Abenavoli, L., Izzo, A. A., Milić, N., Cicala, C., Santini, A., & Capasso, R. (2018). Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytotherapy Research, 32(11), 2202-2213.

https://doi.org/10.1002/ptr.6171

Agarwal, C., Tyagi, A., Kaur, M., & Agarwal, R. (2007). Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells. Carcinogenesis, 28(7), 1463-1470.

https://doi.org/10.1093/carcin/bgm042

Ahn, D. G., Choi, J. K., Taylor, D. R., & Oh, J. W. (2012). Biochemical characterization of a recombinant SARS coronavirus nsp12 RNA-dependent RNA polymerase capable of copying viral RNA templates. Archives of Virology, 157(11), 2095-2104.

https://doi.org/10.1007/s00705-012-1404-x

Bijak, M. (2017). Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.) Chemistry, bioavailability, and metabolism. Molecules, 22(11), 1942.

https://doi.org/10.3390/molecules22111942

Bosch-Barrera, J., Queralt, B., & Menendez, J. A. (2017). Targeting STAT3 with silibinin to improve cancer therapeutics. Cancer Treatment Reviews, 58, 61-69.

https://doi.org/10.1016/j.ctrv.2017.06.003

Carnesecchi, S., Dunand-Sauthier, I., Zanetti, F., Singovski, G., Deffert, C., Donati, Y., Cagarelli T, Pache JC, Krause KH, Reith W, & Barazzone-Argiroffo, C. (2014). NOX1 is responsible for cell death through STAT3 activation in hyperoxia and is associated with the pathogenesis of acute respiratory distress syndrome. International Journal of Clinical and Experimental Pathology, 7(2), 537-551.

Channappanavar, R., Fehr, A. R., Vijay, R., Mack, M., Zhao, J., Meyerholz, D. K., & Perlman, S. (2016). Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host & Microbe, 19(2), 181-193.

https://doi.org/10.1016/j.chom.2016.01.007

Chen, G., Wu, D. I., Guo, W., Cao, Y., Huang, D., Wang, H., Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J., & Ning, Q. (2020). Clinical and immunological features of severe and moderate coronavirus disease 2019. The Journal of Clinical Investigation, 130(5), 2620-2629.

https://doi.org/10.1172/JCI137244

Favalli, E. G., Biggioggero, M., Maioli, G., & Caporali, R. (2020). Baricitinib for COVID-19: a suitable treatment?. The Lancet Infectious Diseases, 20(9), 1012-1013.

https://doi.org/10.1016/S1473-3099(20)30262-0

Fleming, S. B. (2016). Viral inhibition of the IFN-induced JAK/STAT signalling pathway: development of live attenuated vaccines by mutation of viral-encoded IFN-antagonists. Vaccines, 4(3), 23.

https://doi.org/10.3390/vaccines4030023

Gao, H., & Ward, P. A. (2007). STAT3 and suppressor of cytokine signaling 3: potential targets in lung inflammatory responses. Expert Opinion on Therapeutic Targets, 11(7), 869-880.

https://doi.org/10.1517/14728222.11.7.869

Gao, Y., Li, T., Han, M., Li, X., Wu, D., Xu, Y., Zhu Y, Liu Y, Wang X., & Wang, L. (2020). Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID‐19. Journal of Medical Virology, 92(7), 791-796.

https://doi.org/10.1002/jmv.25770

Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., Cao, L., Wang T, Sun Q, Ming Z, Zhang L, Ge J, Zheng L, Zhang Y, Wang H, Zhu Y, Zhu C, Hu T, Hua T, Zhang B, Yang X, Li J, Yang H, Liu Z, Xu W, Guddat LW, Wang Q, Lou Z., & Rao, Z. (2020). Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 368(6492), 779-782.

https://doi.org/10.1126/science.abb7498

Grein, J., Ohmagari, N., Shin, D., Diaz, G., Asperges, E., Castagna, A., Feldt, T., Green, G., Green, L., Lescure, F. X., Nicastri, E., Oda, R., Yo, K., Quiros-Roldan, E., Studemeister, A., Redinski, J., Ahmed, S., Bernett, J., Daniel Chelliah, D., Chen, D., ... & Flanigan, T. (2020). Compassionate use of remdesivir for patients with severe Covid-19. New England Journal of Medicine, 382(24), 2327-2336.

https://doi.org/10.1056/NEJMoa2007016

Guan, W. J., Ni, Z. Y., Hu, Y., Liang, W. H., Ou, C. Q., He, J. X., Liu, L., Shan, H., Lei, C. L., Hui, D.S., Du, B., Li, L. J., Zeng, G., Yuen, K.Y., Chen, R.C., Tang, C. L., Wang, T., Chen, P. Y., Xiang, J., Li, S. Y., ... & Zhong, N. S. (2019). China medical treatment expert group for Covid-19. Clinical Characteristics of Coronavirus Disease, 382(18), 1708-1720.

https://doi.org/10.1056/NEJMoa2002032

Hackett, E. S., Twedt, D. C., & Gustafson, D. L. (2013). Milk thistle and its derivative compounds: a review of opportunities for treatment of liver disease. Journal of Veterinary Internal Medicine, 27(1), 10-16.

https://doi.org/10.1111/jvim.12002

Kim, N. C., Graf, T. N., Sparacino, C. M., Wani, M. C., & Wall, M. E. (2003). Complete isolation and characterization of silybins and isosilybins from milk thistle (Silybum marianum). Organic & Biomolecular Chemistry, 1(10), 1,684-1,689.

https://doi.org/10.1039/b300099k

Kindler, E., & Thiel, V. (2016). SARS-CoV and IFN: too little, too late. Cell Host & Microbe, 19(2), 139-141.

https://doi.org/10.1016/j.chom.2016.01.012

Kirchdoerfer, R. N., & Ward, A. B. (2019). Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nature Communications, 10(1), 1-9.

https://doi.org/10.1038/s41467-019-10280-3

Li, S. W., Wang, C. Y., Jou, Y. J., Yang, T. C., Huang, S. H., Wan, L., Lin, Y. J., & Lin, C. W. (2016). SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway. Scientific Reports, 6(1), 1-13.

https://doi.org/10.1038/srep25754

Liao, M., Liu, Y., Yuan, J., Wen, Y., Xu, G., Zhao, J., Chen, L., Li, J., Wang, X., Wang, F., Liu, L., Zhang, S., & Zhang, Z. (2020). Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19 . Nature Medicine, 26(6),842-844.

https://doi.org/10.1038/s41591-020-0901-9

Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou W., Zhao, L., Chen, J., ... & Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet, 395(10224), 565-574.

https://doi.org/10.1016/S0140-6736(20)30251-8

Pedersen, S. F., & Ho, Y. C. (2020). SARS-CoV-2: a storm is raging. The Journal of Clinical Investigation, 130(5), 2202-2205.

https://doi.org/10.1172/JCI137647

Pérez-Sánchez, A., Cuyàs, E., Ruiz-Torres, V., Agulló-Chazarra, L., Verdura, S., González-Álvarez, I., Bermejo, M., Joven, J., Micol, V., Bosch-Barrera, J., & Menendez, J. A. (2019). Intestinal permeability study of clinically relevant formulations of silibinin in Caco-2 cell monolayers. International Journal of Molecular Sciences, 20(7), 1606.

https://doi.org/10.3390/ijms20071606

Praveen, D., Puvvada, R. C., & Aanandhi, V. (2020). Janus kinase inhibitor baricitinib is not an ideal option for management of COVID-19. International Journal of Antimicrobial Agents, 55(5), 105967.

https://doi.org/10.1016/j.ijantimicag.2020.105967

Priego, N., Zhu, L., Monteiro, C., Mulders, M., Wasilewski, D., Bindeman, W., Doglio L, Martínez L, Martínez-Saez E, Ramón y Cajal S, Megías D, Hernández-Encinas E, Blanco-Aparicio C, Martínez L, Zarzuela E, Muñoz J, Fustero-Torre C, Piñeiro-Yáñez E, Hernández-Laín A, Bertero L, ... & Valiente, M. (2018). STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis. Nature Medicine, 24(7), 1024-1035.

https://doi.org/10.1038/s41591-018-0044-4

Rho, J. K., Choi, Y. J., Jeon, B. S., Choi, S. J., Cheon, G. J., Woo, S. K., Kim H.R., Kim C.H., Choi C.M., & Lee, J. C. (2010). Combined treatment with silibinin and epidermal growth factor receptor tyrosine kinase inhibitors overcomes drug resistance caused by T790M mutation. Molecular Cancer Therapeutics, 9(12), 3233-3243.

https://doi.org/10.1158/1535-7163.MCT-10-0625

Son, Y., Lee, H. J., Rho, J. K., Chung, S. Y., Lee, C. G., Yang, K., Kim, S. H., Lee, M., Shin, I. S., & Kim, J. S. (2015). The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer. BMC Pulmonary Medicine, 15(1), 1-10.

https://doi.org/10.1186/s12890-015-0055-6

Tian, L., Li, W., & Wang, T. (2017). Therapeutic effects of silibinin on LPS-induced acute lung injury by inhibiting NLRP3 and NF-κB signaling pathways. Microbial Pathogenesis, 108, 104-108.

https://doi.org/10.1016/j.micpath.2017.05.011

Tyagi, A., Singh, R. P., Ramasamy, K., Raina, K., Redente, E. F., Dwyer-Nield, L. D., Radcliffe, R. A., Malkinson, A. M., & Agarwal, R. (2009). Growth inhibition and regression of lung tumors by silibinin: modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-κB and signal transducers and activators of transcription 3. Cancer Prevention Research, 2(1), 74-83.

https://doi.org/10.1158/1940-6207.CAPR-08-0095

Verdura, S., Cuyàs, E., Llorach-Parés, L., Pérez-Sánchez, A., Micol, V., Nonell-Canals, A., Joven, J., Valiente, M., Sánchez-Martínez, M., Bosch-Barrera, J., & Menendez, J. A. (2018). Silibinin is a direct inhibitor of STAT3. Food and Chemical Toxicology, 116, 161-172.

https://doi.org/10.1016/j.fct.2018.04.028

World Health Organization. (28 de abril de 2019). Coronavirus Disease (COVID-19) Outbreak. https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

Wu, C., Liu, Y., Yang, Y., Zhang, P., Zhong, W., Wang, Y., Wang, Q., Xu, Y., Li, M., Li, X., Zheng, M., Chen, L., & Li, H. (2020). Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B, 10(5), 766-788.

https://doi.org/10.1016/j.apsb.2020.02.008

Zhang, B., Wang, B., Cao, S., Wang, Y., & Wu, D. (2017). Silybin attenuates LPS-induced lung injury in mice by inhibiting NF-κB signaling and NLRP3 activation. International Journal of Molecular Medicine, 39(5), 1111-1118.

https://doi.org/10.3892/ijmm.2017.2935

Zhang, C., Wu, Z., Li, J. W., Zhao, H., & Wang, G. Q. (2020). Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. International Journal of Antimicrobial Agents, 55(5), 105954.

https://doi.org/10.1016/j.ijantimicag.2020.105954

Zhang, D., Guo, R., Lei, L., Liu, H., Wang, Y., Wang, Y., Qian, H., Dai, T., Zhang, T., Lai, Y., Wang, J., Liu, Z., Chen, T., He, A., O'Dwyer, M., & Hu, J. (2020). COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome. Journal of Leukocyte Biology, 109, 13-22.

https://doi.org/10.1002/JLB.4HI0720-470R

Zhang, J., Luo, Y., Wang, X., Zhu, J., Li, Q., Feng, J., He, D., Zhong, Z., Zheng, X., Lu, J., Zou, D., & Luo, J. (2019). Global transcriptional regulation of STAT3-and MYC-mediated sepsis-induced ARDS. Therapeutic Advances in Respiratory Disease, 13, 1753466619879840.

https://doi.org/10.1177/1753466619879840

Zheng, R., Ma, J., Wang, D., Dong, W., Wang, S., Liu, T., Xie, R., Liu, L., Wang, B., & Cao, H. (2018). Chemopreventive effects of silibinin on colitis-associated tumorigenesis by inhibiting IL-6/STAT3 signaling pathway. Mediators of Inflammation, 2018.

https://doi.org/10.1155/2018/1562010

Ziegler, C. G., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., Cao, y., Yousif, A. S., Blake, J.B., Hauser, M., Feldman, J., Muus, C., Wadsworthll, M. H., Kaser, S. W., Hughes, T. K., Doran, B., Gatter, G. J., Vukovic, M., Taliaferro, F., Mead, B. E., ... & Zhang, K. (2020). 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, 181(5), 1016-1035.

https://doi.org/10.1016/j.cell.2020.04.035