Purpose of a case: use of silymarin / silibinin as a molecular analogue of remdesivir for the treatment of patients diagnosed of COVID-19 with acute mild or moderate respiratory difficulty syndrome. Case report.
DOI:
https://doi.org/10.54495/Rev.Cientifica.v30i2.286Keywords:
SARS-COV2, COVID 19, Optional treatmentAbstract
The respiratory disease caused by SARS-CoV2 is an infectious-contagious viral disease that affects our population, especially older adults and young adults throughout the world. One of the main causes of this pathology is the limited immunization capacity at a global level, especially in developing countries, to combat outbreaks of this disease. It develops in phases of very characteristic respiratory symptoms which can guide an early diagnosis, otherwise it may require hospitalization for treatment; At a global and local level, different therapies have been tried without complete success. Presumptive diagnosis is clinical and confirmatory through nasopharyngeal swabs, which isolate beta virus, SARS-CoV-2 coronavirus, a name issued by the World Health Organization, who declared the pandemic for this disease in particular. A case of a patient with the disease caused by the virus in question is presented who comes to our health home, for not accessing a more complex hospital unit, due to hospital saturation, with a mild to moderate respiratory syndrome, in view of the impossibility of accessing other treatments, we started the administration of silymarin/silibinin in daily doses twice a day. In order for the treatment tested with different molecules to have a common denominator, which is based on attacking the cascade of inflammatory cytokines derived from the activation of the STAT3 receptor and the modulation of type 1 IFG; with corticotherapy mainly dexamethasone, or methylprednisolone, and molecules such as Remdesivir, Sofosbuvir and Ribavirin, which continue to be the focus of discussion, so optional treatments are being evaluated to combat the effects of this disease. The incidence of this disease is global, being higher in underdeveloped countries which do not have an appropriate immunization program.
Downloads
References
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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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. DOI: https://doi.org/10.2139/ssrn.3555145
https://doi.org/10.1016/j.cell.2020.04.035 DOI: https://doi.org/10.1016/j.cell.2020.04.035
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Mauro Antonio Falconi García, Juan Esteban Guevara Betancur
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License 4.0 that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
