CARVEDILOL AS A POTENTIAL ADDITION TO THE COVID-19 THERAPEUTIC ARSENAL
DOI:
https://doi.org/10.22159/ijpps.2020v12i6.38057Keywords:
Carvedilol, SARS-CoV-2, COVID-19Abstract
No single therapeutic agent has been recognized so far as the ultimate treatment for COVID-19 and many treatment strategies rely on associating different medications with proven or hypothetical anti-viral effects. Carvedilol is a third-generation beta-blocker displaying potential inhibitory properties on several key enzymatic processes and pathways involved in SARS-CoV-2 or other coronaviruses replication, in addition to the modulatory effect on several inflammatory messengers of COVID-19. These data could provide a reasonable hypothetical background for further investigating specific anti-SARS-CoV-2 effects and could pave the way for further clinical verification.
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Ma Z, Liu X, Zhang Q, Yu Z, Gao D. Carvedilol suppresses malignant proliferation of mammary epithelial cells through inhibition of the ROS‑mediated PI3K/AKT signaling pathway. Oncol Rep 2019;41:811-8.
Liu B, Liu YJ. Carvedilol promotes retinal ganglion cell survival following optic nerve injury via ASK1-p38 MAPK pathway. CNS Neurol Disord: Drug Targets 2019;18:695-704.
Zawadzka K, Nowak M, Piwonski I, Lisowska K. The synergy of ciprofloxacin and carvedilol against staphylococcus aureus-prospects of a new treatment strategy? Molecules 2019;24:4104.
Kurum T, Tatli E, Yuksel M. Effects of carvedilol on plasma levels of pro-inflammatory cytokines in patients with ischemic and nonischemic dilated cardiomyopathy. Cardiovasc Dis 2007;34:52–9.
Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the anti-viral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents 2020;105938. http://doi:10.1016/j.ijantimicag.2020.105938.
Saijonmaa O, Nyman T, Fyhrquist F. Carvedilol inhibits basal and stimulated ACE production in human endothelial cells. J Cardiovasc Pharmacol 2004;43:616-21.
Meng D, Li Z, Wang G, Ling L, Wu Y, Zhang C. Carvedilol attenuates liver fibrosis by suppressing autophagy and promoting apoptosis in hepatic stellate cells. Biomed Pharmacother 2018;108:1617-27.
Banerjee S, Narayanan K, Mizutani T, Makino S. Murine coronavirus replication-induced p38 mitogen-activated protein kinase activation promotes interleukin-6 production and virus replication in cultured cells. J Virol 2002;76:5937-48.
Park J, Ha H, Kim MS, Ahn HJ, Huh KH, Kim YS. Carvedilol inhibits platelet-derived growth factor-induced extracellular matrix synthesis by inhibiting cellular reactive oxygen species and mitogen-activated protein kinase activation. J Heart Lung Transplant 2006;25:683-9.
Kalinowski L, Dobrucki LW, Szczepanska Konkel M, Jankowski M, Martyniec L, Angielski S, et al. Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action. Circulation 2003;107:2747-52.
Akerstrom S, Mousavi Jazi M, Klingstrom J, Leijon M, Lundkvist A, Mirazimi A. Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol 2005;79:1966-9.
Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharma Sin B 2020. https://doi.org/10.1016/j.apsb.2020.02.008
Nash CA, Wei W, Irannejad R, Smrcka AV. Golgi localized β1-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLCε to regulate cardiac hypertrophy. Elife 2019;8:e48167. https://doi:10.7554/eLife.48167
Yang Z, Kirton HM, MacDougall DA, Boyle JP, Deuchars J, Frater B, et al. The Golgi apparatus is a functionally distinct Ca2+store regulated by the PKA and Epac branches of the β1-adrenergic signaling pathway. Sci Signal 2015;8:ra101.
Brignoni M, Pignataro OP, Rodriguez ML, Alvarez A, Vega Salas DE, Rodriguez-Boulan E, et al. Cyclic AMP modulates the rate of 'constitutive' exocytosis of apical membrane proteins in Madin-Darby canine kidney cells. J Cell Sci 1995;108:1931-43.
Xiaohua C, Binghong Z, Yueming Q, Yurou C, Jie X, Yong F, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. medRxiv 2020. https://doi.org/10.1101/2020.02.29.20029520
Herold T, Jurinovic V, Arnreich C, Hellmuth JC, Von Bergwelt-Baildon M, Klein M, et al. Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. medRxiv 2020. https://doi.org/10.1101/2020.04.01.20047381
Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci Chin Life Sci 2020;63:364-74.
DeDiego ML, Nieto Torres JL, Regla Nava JA, Jimenez Guardeno JM, Fernandez-Delgado R, et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol 2014;88:913-24.
Yang SP, Ho LJ, Lin YL, Cheng SM, Tsao TP, Chang DM, Hsu YL, et al. Carvedilol, a new antioxidative beta-blocker, blocks in vitro human peripheral blood T cell activation by downregulating NF-kappa B activity. Cardiovasc Res 2003;59:776-87.
Blumenfeld JD, Sealey JE, Mann SJ, Bragat A, Marion R, Pecker MS, et al. Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects. Am J Hypertens 1999;12:451-9.
Baglivo M, Baronio M, Natalini G, Beccari T, Chiurazzi P, Fulcheri E, et al. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? Acta Biomed 2020;91:161-4.
Pratelli A, Colao V. Role of the lipid rafts in the life cycle of canine coronavirus. J Gen Virol 2015;96:331-7.
Glende J, Schwegmann Wessels C, Al-Falah M, Pfefferle S, Qu X, Deng H, et al. Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2. Virology 2008;381:215–21.
Wen X, Tan F, Jing Z, Liu Z. Preparation and study the 1:2 inclusion complex of carvedilol with beta-cyclodextrin. J Pharm Biomed Anal 2004;34:517-23.
CK Oh Assignee, Smith Kline Beecham. Novel formulations of carvedilol. Patent No: WO03028649; 2003.
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Anti-viral Res 2020. https://doi.org/10.1016/ j.antiviral.2020.104787.
