Actuality. Severe acute respiratory syndrome- (SARS) is a pandemic (called as SARS-CoV-2 or COVID-19), severely affected by transmission and fatal disease caused by unknown coronavirus family of RNA virus (SARS-COV). The phenotype can range from asymptomatic to fulminate cytokine storm which leads to multiorgan failure resulting in death. Still, the world is eagerly waiting for antiviral drugs to stop the coronavirus infection. Previous studies found that indomethacin had the ability to inhibit the RNA and DNA virus replication.
Objectives. Discuss the possibility of clinical treatment of inflammation caused by SARS-COV-2 with indomethacin.
Materials and methods. Analysis of scientific publications in the international electronic scientometric database PubMed by keywords for the period 1991-2020. Comparison with clinical cases.
Results. Interleukins, Interferons, and metabolites formed by the enzyme cyclooxygenase (COX 1/COX 2) are active against some RNA viruses. Experts have divided the SARS infection into three phases (phase-1, 2, 3) based on the severity of the infection. In phase-3 there was “cytokine storm” due to exuberant inflammation observed which can damage organs and even fatal. We investigated the effect of indomethacin on the COX inhibitor on coronavirus replication and cytokine storm in reducing the hyperinflammatory state. Indomethacin is a potent inhibitor of SARS CoV-2.
Conclusion. Indomethacin can be considered safe and effective for the prevention and treatment of coronavirus infection also antiviral activity.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 January 24; 395 (10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5
Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Feb 03; 579: 270-273. https://doi.org/10.1038/s41586-020-2012-7
Xu H, Zhong L, Deng J, Peng J., Dan H., Zeng X., Li T. & Chen Q. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020 Feb 24; 12: article 8. https://doi.org/10.1038/s41368-020-0074-x
Cao Y., Li L., Feng Z., Wan Sh., P. Huang, Sun X., Wen F., Huang X., Ning G. & Wang W. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discovery. 2020 Feb 24; 6(1): article 11. https://doi.org/10.1038/s41421-020-0147-1
Shi1 Y., Wang Y., Shao Ch., Huang J., Gan J., Huang X., Bucci E., Piacentini M., Ippolito G., Melino G. COVID-19 infection: the perspectives on immune responses. Cell Death & Differentiation. Cell Death & Differentiation. 2020 March 23. 27: 1451-4. https://doi.org/10.1038/s41418-020-0530-3 https://doi.org/10.1038/s41418-020-0530-3
Goodman RB, Strieter RM, Martin DP, Steinberg KP, Milberg JA, Maunder RJ, Kunkel SL, Walz A, Hudson LD, Martin TR. Inﬂammatory cytokines in patients with persistence of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1996;154:602-11. PMID: 8810593. https://doi.org/10.1164/ajrccm.154.3.8810593
Arend WP. Interleukin-1 receptor antagonist. Adv Immunol. 1993; 54: 167-227. PMID: 8379462. https://doi.org/10.1016/s0065-2776(08)60535-0
Burger D, Chicheportiche R, Giri JG, Dayer JM. The inhibitory activity of human interleukin-1 receptor antagonist is enhanced by type II interleukin-1 soluble receptor and hindered by type I interleukin-1 soluble receptor. J Clin Invest. 1995 July 1; 96: 38-41. PMID: 7615809. https://doi.org/10.1172/jci118045
Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, Kritas SK. Induction of pro- inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. Journal of Biological Regulators and Homeostatic Agents. 2020 Mar 01; 34(2):327-31. PMID: 32171193. https://doi.org/10.23812/conti-e
Brunton LL, Parker L, Blumenthal DK, Buxton ILO. Goodman and Gilman’s Manual of Pharmacology and Therapeutics. New York: McGraw-Hill Medical, 2008:446-47.
Amici C, Di Caro A, Ciucci A, Chiappa L., Castilletti C., Martella V., Decaro N., Buonavoglia C., Capobianchi M.R., Santoro M.G. Indomethacin has a potent antiviral activity against SARS coronavirus. Antivir Ther 2006;11(8):1021-30. PMID: 17302372. https://pubmed.ncbi.nlm.nih.gov/17302372/
Brunton LL, Parker L, Blumenthal DK, Buxton ILO. Goodman and Gilman’s Manual of Pharmacology and Therapeutics. New York, NY: McGraw‐Hill Medical; 2008: 446‐7.
Day M. Covid‐19: ibuprofen should not be used for managing symptoms say doctors and scientists. BMJ. 2020 March 17; 368: m1086. https://doi.org/10.1136/bmj.m1086
Gupta R, Misra A. Contentious issues and evolving concepts in the clinical presentation and management of patients with COVID‐19 infection with reference to use of therapeutic and other drugs used in co‐morbid diseases (Hypertension, diabetes, etc.). Diabetes Metab Syndr. 2020; 14(3): 251‐4. PMID: 32247213. https://doi.org/10.1016/j.dsx.2020.03.012
Updated: WHO now doesn’t recommend avoiding ibuprofen for COVID‐19 symptoms. https://www.sciencealert.com/who‐recommends‐to‐avoid‐taking‐ibuforfin‐for‐covid‐19‐symptoms.
Chmiel JF, Konstan MW, Accurso FJ, Lymp J, Mayer-Hamblett H, VanDevanter DR, Rose LM, Ramsey BW, Assessment of Induced Sputum in Cystic Fibrosis Study Group. Use of ibuprofen to assess inflammatory biomarkers in induced sputum: implications for clinical trials in cystic fibrosis. J Cyst Fibros. 2015 Nov; 14(6): 720‐6. PMID: 25869324. https://doi.org/10.1016/j.jcf.2015.03.007
Zhang W, Zhao Y, Zhang F,Wang Q.,Li T., Liu Z., Wang J., Qin Y., Zhang X., Yan X., Zeng, and Zhang Sh. The use of anti‐inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID‐19): the perspectives of clinical immunologists from China. Clin Immunol. 2020 Mar 25; 214: 108393. PMID: 32222466. https://dx.doi.org/10.1016%2Fj.clim.2020.108393
Lucas S. The Pharmacology of Indomethacin. Headache. 2016 Feb 11; 56(2): 436-46. https://doi.org/10.1111/head.12769
Draper MP, Martell RL, Levy SB. Indomethacin-mediated reversal of multidrug resistance and drug efflux in human and murine cell lines overexpressing MRP, but not P-glycoprotein. Br. J. Cancer. 1997; 75(6): 810-5. PMID: 9062400. https://doi.org/10.1038/bjc.1997.145
Vane JR, Botting RM. Mechanism of action of anti-inflam-matory drugs. Scand J Rheumatol Suppl. 1996;102:9-21. PMID: 8628981. https://doi.org/10.3109/03009749609097226
Tegeder I, Pfeilschifter J, Geisslinger G. Cyclooxygenase- independent actions of cyclooxygenase inhibitors. FASEB J 2001 Oct; 15(12):2057-72. PMID: 11641233. https://doi.org/10.1096/fj.01-0390rev
Amici C, La Frazia S, Brunelli C, Balsamo M, Angelini M, Santoro MG. Inhibition of viral protein translation by indomethacin in vesicular stomatitis virus infection: role of eIF2α kinase PKR. Cell. Microbiol. 2015 Sep;17(9):1391-404. PMID: 25856684.https://dx.doi.org/10.1111%2Fcmi.12446
Hoppmann RA, Peden JG, Ober SK. Central nervous system side effects of nonsteroidal anti-inflammatory drugs. Aseptic meningitis, psychosis, and cognitive dysfunction. Arch. Intern. Med. 1991 Jul;151(7):1309-13. PMID: 2064481
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