Antioxidants and COVID-19

Silvio DE Flora, Roumen Balansky, Sebastiano LA Maestra, Silvio DE Flora, Roumen Balansky, Sebastiano LA Maestra

Abstract

Conflict of interest statement

Conflict of interest statement The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Some agents endowed with antioxidant properties that have been shown or suspected to play a role in COVID-19 prevention and/or adjuvant therapy. The quercetin formula is shown as an example of flavonoids and curcumin is shown as an example of Nrf2 activators.
Fig. 2.
Fig. 2.
Schematic representation of the glutathione cycle and ability of thiols to scavenge ROS. Abbreviations: GSH, reduced glutathione; GSSG, oxidized glutathione; GR, glutathione reductase; GPx, glutathione peroxidase; GLC, glutamate cysteine ligase; L-Cys, L-Cysteine; NAC, N-acetylcysteine; ROS, reactive oxygen species.
Fig. 3.
Fig. 3.
NAC and GSH trigger two parallel channels that attenuate inflammation either by inhibiting NFκB-dependent pro-inflammatory genes and/or by stimulating Nrf2-dependent anti-inflammatory genes (see Text for details).

References

    1. Oter S, Jin S, Cucullo L, Dorman HJ. Oxidants and antioxidants: friends or foes? Oxid Antioxid Med Sci 2012;1:1-4.
    1. Pryor WA, Prier DG, Church DF. Electron-spin resonance study of mainstream and sidestream cigarette smoke: nature of the free radicals in gas-phase smoke and in cigarette tar. Environ Health Perspect 1983;47:345-55.
    1. Kontoghiorghes GJ, Kolnagou A, Kontoghiorghe CN, Mourouzidis L, Timoshnikov VA, Polyakov NE. Trying to solve the puzzle of the interaction of ascorbic acid and iron: redox, chelation and therapeutic implications. Medicines (Basel) 2020;7:E45.
    1. García-Sánchez A, Miranda-Díaz AG, Cardona-Muñoz EG. The role of oxidative stress in physiopathology and pharmacological treatment with pro- and antioxidant properties in chronic diseases. Oxid Med Cell Longev 2020;2020:2082145.
    1. Delgado-Roche L, Mesta F. Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Arch Med Res 2020;51:384-7.
    1. Khomich OA, Kochetkov SN, Bartosch B, Ivanov AV. Redox biology of respiratory viral infections. Viruses 2018;10:392.
    1. Komaravelli N, Casola A. Respiratory viral infections and subversion of cellular antioxidant defenses. J Pharmacogenomics Pharmacoproteomics 2014;5:1000141.
    1. De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J 1997;10:1535-41.
    1. Mata M, Morcillo E, Gimeno C, Cortijo J. N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV). Biochem Pharmacol 2011;82:548-55.
    1. Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J, Jr. N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochem Pharmacol 2010;1:79:413-20.
    1. Zhang RH, Li CH, Wang CL, Xu M-J, Xu T, Wei D, Liu B-J, Wang G-H, Tian S-F. N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury. Int Immunopharmacol 2014;22:1-8.
    1. Ghezzi P, Ungheri D. Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model. Int J Immunopathol Pharmacol 2004;17:99-102.
    1. Garozzo A, Tempera G, Ungheri D, Timpanaro R, Castro A. N-acetylcysteine synergizes with oseltamivir in protecting mice from lethal influenza infection. Int J Immunopathol Pharmacol 2007;20:349-54.
    1. Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol 2020;20:269-70.
    1. Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal 2020;10:102-8. . 10.1016/j.jpha.2020.03.001
    1. Puelles VG, Lütgehetmann M, Lindenmeyer MT, Sperhake JP, Wong MN, Allweiss L, Chilla S, Heinemann A, Wanner N, Liu S, Braun F, Lu S, Pfefferle S, Schröder AS, Edler C, Gross O, Glatzel M, Wichmann D, Wiech T, Kluge S, Pueschel K, Aepfelbacher M, Huber TB. Multiorgan and Renal Tropism of SARS-CoV-2. N Engl J Med 2020;383:590-592. . 10.1056/NEJMc2011400
    1. Lang JP, Wang X, Moura FA, Siddiqi HK, Morrow DA, Bohula EA. A current review of COVID-19 for the cardiovascular specialist. Am Heart J 2020;226:29-44. . 10.1016/j.ahj.2020.04.025
    1. Divani AA, Andalib S, Di Napoli M, Lattanzi S, Hussain MS, Biller J, McCullough LD, Azarpazhooh MR, Seletska A, Mayer SA, Torbey M. Coronavirus Disease 2019 and stroke: clinical manifestations and pathophysiological insights. J Stroke Cerebrovasc Dis 2020;29:104941.
    1. van den Brand JM, Haagmans BL, van Riel D, Osterhaus AD, Kuiken T. The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. J Comp Pathol 2014;151:83-112.
    1. Schönrich G, Raftery MJ, Samstag Y. Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression. Adv Biol Regul 2020;77:100741.
    1. Blaser H, Dostert C, Mak TW, Brenner D. TNF and ROS Crosstalk in Inflammation. Trends Cell Biol 2016;26:249-61.
    1. Sandoval R, Lazcano P, Ferrari F, Pinto-Pardo N, González-Billault C, Utreras E. TNF-α increases production of reactive oxygen species through Cdk5 activation in nociceptive neurons. Front Physiol 2018;9:65.
    1. Checconi P, De Angelis M, Marcocci ME, Fraternale A, Magnani Palamara AT, Nencioni L. Redox-modulating agents in the treatment of viral infections. Int J Mol Sci 2020;21:4084.
    1. Wu J. Tackle the free radicals damage in COVID-19. Nitric Oxide 2020;102:39-41.
    1. Soto ME, Guarner-Lans V, Soria-Castro E, Manzano Pech L, Pérez-Torres I. Is Antioxidant therapy a useful complementary measure for Covid-19 treatment? An algorithm for its application. Medicina (Kaunas) 2020;56:386.
    1. Diniz LRL, Bezerra Filho CDSM, Fielding BC, de Sousa DP. Natural antioxidants: a review of studies on human and animal coronavirus. Oxid Med Cell Longev 2020;2020:3173281.
    1. Iddir M, Brito A, Dingeo G, Fernandez Del Campo S, Samouda H, La Frano MR, Bohn T. Strengthening the immune system and reducing inflammation and oxidative stress through diet and nutrition: considerations during the COVID-19 crisis. Nutrients 2020;12:1562.
    1. Emerald M. Nutrients in prevention and maintenance of COVID-19 and other viral diseases. In: Functional Foods and Viral Diseases, First Edition, Chapter 8. Dallas, TX, USA: Food Science Publisher; 2020, pp. 175-202.
    1. BourBour F, Mirzaei Dahka S, Gholamalizadeh M, Akbari ME, Shadnoush M, Haghighi M, Taghvaye-Masoumi H, Ashoori N, Doaei S. Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus. Arch Physiol Biochem 2020:1-10.
    1. Russo M, Moccia S, Spagnuolo C, Tedesco I, Russo GL. Roles of flavonoids against coronavirus infection. Chem Biol Interact. 2020;328:109211.
    1. Levy E, Delvin E, Marcil V, Spahis S. Can phytotherapy with polyphenols serve as a powerful approach for the prevention and therapy tool of novel coronavirus disease 2019 (COVID-19)? Am J Physiol Endocrinol Metab 2020;319:E689-E708.
    1. Colunga Biancatelli RML, Berrill M, Catravas JD, Marik PE. Quercetin and vitamin C: an experimental, synergistic therapy for the prevention and treatment of SARS-CoV-2 related disease (COVID-19). Front Immunol 2020;11:1451.
    1. Abian O, Ortega-Alarcon D, Jimenez-Alesanco A, Ceballos Laita L, Vega S, Reyburn HT, Rizzuti B, Velazquez-Campoy A. Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening. Int J Biol Macromol 2020;164:1693-703.
    1. Loffredo L, Violi F. COVID-19 and cardiovascular injury: a role for oxidative stress and antioxidant treatment? Int J Cardiol 2020;312:136.
    1. Obi J, Pastores SM, Ramanathan LV, Yang J, Halpern NA. Treating sepsis with vitamin C, thiamine, and hydrocortisone: exploring the quest for the magic elixir. J Crit Care 2020;57:231-9.
    1. Liu F, Zhu Y, Zhang J, Li Y, Peng Z. Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial. BMJ Open 2020;10:e039519.
    1. Bahrampour Juybari K, Pourhanifeh MH, Hosseinzadeh A, Hemati K, Mehrzadi S. Melatonin potentials against viral infections including COVID-19: current evidence and new findings. Virus Res 2020;287:198108.
    1. Feitosa EL, Júnior FTDSS, Nery Neto JAO, Matos LFL, Moura MHS, Rosales TO, De Freitas GBL. COVID-19: rational discovery of the therapeutic potential of melatonin as a SARS-CoV-2 main protease inhibitor. Int J Med Sci 2020;17:2133-46.
    1. El-Missiry MA, El-Missiry ZMA, Othman AI. Melatonin is a potential adjuvant to improve clinical outcomes in individuals with obesity and diabetes with coexistence of Covid-19. Eur J Pharmacol 2020;882:173329.
    1. Shneider A, Kudriavtsev A, Vakhrusheva A. Can melatonin reduce the severity of COVID-19 pandemic? Int Rev Immunol 2020;39:153-62.
    1. Acuña-Castroviejo D, Escames G, Figueira JC, de la Oliva P, Borobia AM, Acuña-Fernández C. Clinical trial to test the efficacy of melatonin in COVID-19. J Pineal Res 2020;69:e12683.
    1. Pahan P, Pahan K. Smooth or risky revisit of an old malaria drug for COVID-19? J Neuroimmune Pharmacol 2020;15:174-80.
    1. Ibrahim H, Perl A, Smith D, Lewis T, Kon Z, Goldenberg R, Yarta K, Staniloae C, Williams M. Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine. Clin Immunol 2020;219:108544.
    1. Zhong LLD, Lam WC, Yang W, Chan KW, Sze SCW, Miao J, Yung KKL, Bian Z, Wong VT. Potential targets for treatment of Coronavirus Disease 2019 (COVID-19): a review of Qing-Fei-Pai-Du-Tang and its major herbs. Am J Chin Med 2020;48:1051-71.
    1. McCord JM, Hybertson BM, Cota-Gomez A, Geraci KP, Gao B. Nrf2 Activator PB125® as a potential therapeutic agent against COVID-19. Antioxidants (Basel) 2020;9:518.
    1. Liu Z, Ying Y. The inhibitory effect of curcumin on virus-induced cytokine storm and its potential use in the associated severe pneumonia. Front Cell Dev Biol 2020;8:479.
    1. Menegazzi M, Campagnari R, Bertoldi M, Crupi R, Di Paola R, Cuzzocrea S. Protective effect of epigallocatechin-3-gallate (EGCG) in diseases with uncontrolled immune activation: could such a scenario be helpful to counteract COVID-19? Int J Mol Sci 2020;21:5171.
    1. Mendonca P, Soliman KFA. Flavonoids activation of the transcription factor Nrf2 as a hypothesis approach for the prevention and modulation of SARS-CoV-2 infection severity. Antioxidants (Basel) 2020;9:659.
    1. De Flora S, Balansky R, La Maestra S. Rationale for the use of N-acetylcysteine in both prevention and adjuvant therapy of COVID-19. FASEB J 2020;34:13185-93.
    1. Zhang J, Taylor EW, Bennett K, Saad R, Rayman MP. Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr 2020;111:1297-9.
    1. Moghaddam A, Heller RA, Sun Q, Seelig J, Cherkezov A, Seibert L, Hackler J, Seemann P, Diegmann J, Pilz M, Bachmann M, Minich WB, Schomburg L. Selenium deficiency Is associated with mortality risk from COVID-19. Nutrients 2020;12:2098.
    1. Seale LA, Torres DJ, Berry MJ, Pitts MW. A role for selenium-dependent GPX1 in SARS-CoV-2 virulence. Am J Clin Nutr 2020;112:447-8.
    1. Hiffler L, Rakotoambinina B. Selenium and RNA virus interactions: potential implications for SARS-CoV-2 infection (COVID-19). Front Nutr 2020;7:164.
    1. Alexander J, Tinkov A, Strand TA, Alehagen U, Skalny A, Aaseth J. Early nutritional interventions with zinc, selenium and vitamin D for raising anti-viral resistance against progressive COVID-19. Nutrients 2020;12:2358.
    1. Sies H, Parnham MJ. Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections. Free Radic Biol Med. 2020;156:107-12.
    1. Polonikov A. Endogenous Deficiency of Glutathione as the Most Likely Cause of serious manifestations and death in COVID-19 patients. ACS Infect Dis 2020;6:1558-62.
    1. Silvagno F, Vernone A, Pescarmona GP. The role of glutathione in protecting against the severe inflammatory response triggered by COVID-19. Antioxidants (Basel) 2020;9:624.
    1. Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI. The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem 2007;113:234-58.
    1. Cao M, Zhang D, Wang Y, Lu Y., Zhu X, Ying Li, Xue H, Lin Y, Zhang M, Sun Y, Yang Z, Shi J, Wang Y, Zhou C, Dong Y, Liu P, Dudek SM, Xiao Z, Lu H, Peng L. Clinical features of patients infected with the 2019 novel coronavirus (COVID-19) in Shanghai, China. medRxiv 2020.
    1. Taylor EW, Radding W. Understanding selenium and glutathione as antiviral factors in COVID-19: does the viral Mpro protease target host selenoproteins and glutathione synthesis? Front Nutr 2020;7:143.
    1. Guloyan V, Oganesian B, Baghdasaryan N, Yeh C, Singh M, Guilford F, Ting YS, Venketaraman V. Glutathione supplementation as an adjunctive therapy in COVID-19. Antioxidants (Basel) 2020;9:E914.
    1. Horowitz RI, Freeman PR, Bruzzese J. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: a report of 2 cases. Respir Med Case Rep 2020;30:101063.
    1. Hati S, Bhattacharyya S. Impact of thiol-disulfide balance on the binding of Covid-19 spike protein with Angiotensin Converting Enzyme 2 receptor. bioRxiv 2020.
    1. Capettini LS, Montecucco F, Mach F, Stergiopulos N, Santos RA, da Silva RF. Role of renin-angiotensin system in inflammation, immunity and aging. Curr Pharm Des 2012;18:963-70.
    1. Basi Z, Turkoglu V. In vitro effect of oxidized and reduced glutathione peptides on angiotensin converting enzyme purified from human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2019;1104:190-5.
    1. Boesgaard S, Aldershvile J, Poulsen HE, Christensen S, Dige-Petersen H, Giese J. N-acetylcysteine inhibits angiotensin converting enzyme in vivo. J Pharmacol Exp Ther 1993;265:1239-44.
    1. Raftos JE, Whillier S, Chapman BE, Kuchel PW. Kinetics of uptake and deacetylation of N-acetylcysteine by human erythrocytes. Int J Biochem Cell Biol 2007;39:1698-706.
    1. Lu SC. Regulation of glutathione synthesis. Mol Aspects Med 2009;30:42-59.
    1. Ruffmann R, Wendel A. GSH rescue by N-acetylcysteine. Klin Wochenschr 1991;69:857-62.
    1. Wong BK, Chan HC, Corcoran GB. Selective effects of N-acetylcysteine stereoisomers on hepatic glutathione and plasma sulfate in mice. Toxicol Appl Pharmacol 1986;86:421-9.
    1. Sadowska AM. N-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary disease. Ther Adv Respir Dis 2012;6:127-35.
    1. Šalamon Š, Kramar B, Marolt TP, Poljšak B, Milisav I. Medical and dietary uses of N-acetylcysteine. Antioxidants (Basel) 2019;8:111.
    1. Haddad JJ. Glutathione depletion is associated with augmenting a proinflammatory signal: evidence for an antioxidant/pro-oxidant mechanism regulating cytokines in the alveolar epithelium. Cytokines Cell Mol Ther 2000;6:177-87.
    1. Feng F, Zhang J, Wang Z, Wu Q, Zhou X. Efficacy and safety of N-acetylcysteine therapy for idiopathic pulmonary fibrosis: an updated systematic review and meta-analysis. Exp Ther Med 2019;18:802-16.
    1. Lee YH, Kim CH, Lee J. Coronavirus disease 2019 pneumonia may present as an acute exacerbation of idiopathic pulmonary fibrosis. J Thorac Dis 2020;12:3902-4.
    1. Zhan X, Liu B, Tong ZH. Postinflammatroy pulmonary fibrosis of COVID-19: the current status and perspective. Zhonghua Jie He He Hu Xi Za Zhi 2020;43:728-32.
    1. Bernard GR, Wheeler AP, Arons MM, Morris PE, Paz HL, Russell JA, Wright PE. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Chest 1997;112:164-72.
    1. Soltan-Sharifi MS, Mojtahedzadeh M, Najafi A, Reza Khajavi M, Reza Rouini M, Moradi M, Mohammadirad A, Abdollahi M. Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms. Hum Exp Toxicol 2007;26:697-703.
    1. Pacht ER, Timerman AP, Lykens MG, Merola AJ. Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome. Chest 1991;100:1397-403.
    1. Dharsandiya M, Shah K, Patel K, Patel T, Patel A, Patel A. SARS-CoV-2 viral sepsis with meningoencephalitis. Indian J Med Microbiol 2020;38:219-21.
    1. Ershad M, Wermuth HR, Vearrier D. N Acetylcysteine. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.
    1. Carothers C, Birrer K, Vo M. Acetylcysteine for the treatment of suspected remdesivir-associated acute liver failure in COVID-19: a case series. Pharmacotherapy 2020:10.1002/phar.2464.
    1. Vardavas CI, Nikitara K. COVID-19 and smoking: A systematic review of the evidence. Tob Induc Dis 2020;18:20.
    1. Bazzini C, Rossetti V, Civello DA, Sassone F, Vezzoli V, Persani L, Tiberio L, Lanata L, Bagnasco M, Paulmichl M, Meyer G, Garavaglia ML. Short- and long- term effects of cigarette smoke exposure on glutathione homeostasis in human bronchial epithelial cells. Cell Physiol Biochem 2013;32:129-45.
    1. van der Toorn M, Smit-de Vries MP, Slebos DJ, de Bruin HG, Abello N, van Oosterhout AJ, Bischoff R, Kauffman HF. Cigarette smoke irreversibly modifies glutathione in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 2007;293:L1156-62.
    1. Gould NS, Min E, Huang J, Chu HW, Good J, Martin RJ, Day BJ. Glutathione depletion accelerates cigarette smoke-induced inflammation and airspace enlargement. Toxicol Sci 2015;147:466-74.
    1. De Flora S, Izzotti A, D’Agostini F, Balansky RM. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis 2001;22:999-1013.
    1. van Schooten FJ, Besaratinia A, De Flora S, D’Agostini F, Izzotti A, Camoirano A, Balm AJ, Dallinga JW, Bast A, Haenen GR, Van’t Veer L, Baas P, Sakai H, Van Zandwijk N. Effects of oral administration of N-acetyl-L-cysteine: a multi-biomarker study in smokers. Cancer Epidemiol Biom Prev 2002:11;167-75.
    1. Aruoma OI, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 1989;6:593-7.
    1. Tardiolo G, Bramanti P, Mazzon E. Overview on the effects of N-acetylcysteine in neurodegenerative diseases. Molecules 2018;23:3305.
    1. Hui DS, Lee N. Adjunctive therapies and immunomodulating agents for severe influenza. Influenza Other Respir Viruses 2013;7,3:52-9.
    1. Zhou Y, Wang HD, Zhou XM, Fang J, Zhu L, Ding K.N-acetylcysteine amide provides neuroprotection via Nrf2-ARE pathway in a mouse model of traumatic brain injury. Drug Des Devel Ther 2018;12:4117-27.
    1. Zhao N, Guo FF, Xie KQ, Zeng T. Targeting Nrf-2 is a promising intervention approach for the prevention of ethanol-induced liver disease. Cell Mol Life Sci 2018;75:3143-57.
    1. Wagener FADTG, Pickkers P, Peterson SJ, Immenschuh S, Abraham NG. Targeting the heme-heme oxygenase system to prevent severe complications following COVID-19 infections. Antioxidants (Basel) 2020;9:E540.
    1. Liu M, Pelling JC, Ju J, Chu E, Brash DE. Antioxidant action via p53-mediated apoptosis. Cancer Res 1998;58:1723-9.
    1. Loscalzo J. Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circ Res 2001;88:756-62.
    1. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000;86:494-501.
    1. Guglielmetti G, Quaglia M, Sainaghi PP, Castello LM, Vaschetto R, Pirisi M, Corte FD, Avanzi GC, Stratta P, Cantaluppi V. “War to the knife” against thromboinflammation to protect endothelial function of COVID-19 patients. Crit Care 2020;24:365.
    1. Zuin R, Palamidese A, Negrin R, Catozzo L, Scarda A, Balbinot M. High-dose N-acetylcysteine in patients with exacerbations of chronic obstructive pulmonary disease. Cl Drug Invest 2005;25:401-8.
    1. Qi Q, Ailiyaer Y, Liu R, Zhang Y, Li C, Liu M, Wang X, Jing L, Li Y. Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial. Respir Res 2019;20:73.
    1. Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, Sergio F. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res 2018;52:751-62. . 10.1080/10715762.2018.1468564
    1. Wallace JL, Blackler RW, Chan MV, Da Silva GJ, Elsheikh W, Flannigan KL, Gamaniek I, Manko A, Wang L, Motta JP, Buret AG. Anti-inflammatory and cytoprotective actions of hydrogen sulfide: translation to therapeutics. Antioxid Redox Signal 2015;22:398-410.
    1. Andreou A, Trantza S, Filippou D, Sipsas N, Tsiodras S. COVID-19: The potential role copper and N-acetylcysteine (NAC) in a combination of candidate antiviral treatments against SARS-CoV-2. In Vivo 2020;34:1567-88.
    1. Bauer SR, Kapoor A, Rath M, Thomas SA. What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19? Cleve Clin J Med 2020.
    1. Gasmia A, Tippairoteb T, Mujawdiyad PK, Peana M, Menzelf A, Dadarg M, Gasmi Benahmedh A, Bjørklund G. Micronutrients as immunomodulatory tools for COVID-19 management. Clin Immunol 2020;220:108545.
    1. Jaiswal N, Bhatnagarb M, Shahc H. N-acetycysteine: A potential therapeutic agent in COVID-19 infection. Medical Hypotheses 2020;144:110133.
    1. McCarty MF, DiNicolantonio JJ. Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus. Prog Cardiovasc Dis 2020;S0033-0620(20)30037-2.
    1. Nasi A, McArdle S, Gaudernack G, Westman G, Melief C, Rockberg J, Arens R, Kouretas D, Sjölin J, Mangsbo S. Reactive oxygen species as an initiator of toxic innate immune responses in retort to SARS-CoV-2 in an ageing population, consider N-acetylcysteine as early therapeutic intervention. Toxicol Rep 2020;18:768-71.
    1. Poe FL, Corn J. N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2. Med Hypotheses 2020;143:109862. . 10.1016/j.mehy.2020.109862
    1. Jorge-Aarón RM, Rosa-Ester MP. N-acetylcysteine as a potential treatment for COVID-19. Future Microbiol 2020;15:959-62.
    1. Sahebnasagh A, Saghafi F, Avan R, A, Khoshi A, Khataminia M, Safdari M, Habtemariam S, Rezai Ghaleno H, Nabavi SM. The prophylaxis and treatment potential of supplements for COVID-19. Eur J Pharmacol 2020;1:173530. . 10.1016/j.ejphar.2020.173530
    1. Spearow JL, Copeland L. Review: improving therapeutics for COVID-19 with glutathione-boosting treatments that improve immune responses and reduce the severity of viral infections. 2020.
    1. Tolosa MTS, Genuino RF. Should N-acetylcysteine be used as adjunct treatment for COVID-19? Asia Pacific Center for Evidence Based Healthcare 2020. Available at: (accessed on: October 3, 2020).
    1. van Hecke O, Lee J. N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19. 2020. - . Available at: (accessed on: October 6, 2020).
    1. Al-Horani RA, Kar S. Potential anti-SARS-CoV-2 therapeutics that target the post-entry stages of the viral life cycle: a comprehensive review. Viruses 2020;12:E1092.
    1. Sharafkhah M, Abdolrazaghnejad A, Zarinfar N, Mohammadbeigi A, Massoudifar A, Abaszadeh S. Safety and efficacy of N-acetyl-cysteine for prophylaxis of ventilator-associated pneumonia: a randomized, double blind, placebo-controlled clinical trial. Med Gas Res 2018;8:19-23.
    1. Bhattacharya R, Mondal M, Naiya SB, Lyngdoh L, Mukherjee R, Singh PK. The beneficial role of N-acetylcysteine as an adjunctive drug in treatment of COVID-19 patients in a tertiary care hospital in India: an observational study. Int J Res Med Sci 2020;8:3518-22. 10.18203/2320-6012.ijrms20204010
    1. Sestili P, Fimognari C. Paracetamol use in COVID-19: friend or enemy? Preprints 2020,2020080186.
    1. Sestili P, Fimognari C. Paracetamol-induced glutathione consumption: is there a link with severe COVID-19 illness? Front Pharmacol 2020. 10.3389/fphar.2020.579944
    1. de Alencar JCG, de Lucena Moreira C, Dudy Müller A, Chaves CE, Akemi Fukuhara M, da Silva EA, Miyamoto MFS, Barbosa Pinto V, Gasparotto Bueno C, Neto FL, Gomez LM, Saad Menezes MC, Meirelles Marchini JF, Oliveira Marino L, Neto RAB, Souza HP, Covid Register Group . Double-blind, randomized, placebo-controlled trial with N-acetylcysteine for treatment of severe acute respiratory syndrome caused by COVID-19. Clin Inf Dis 2020;72:e736-e741.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren