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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

The Association of Respiratory Viruses with Oxidative Stress and Antioxidants. Implications for the COVID-19 Pandemic

Author(s): Marina Darenskaya*, Liubov Kolesnikova and Sergei Kolesnikov

Volume 27, Issue 13, 2021

Published on: 22 February, 2021

Page: [1618 - 1627] Pages: 10

DOI: 10.2174/1381612827666210222113351

Price: $65


The spread of a new strain of coronavirus, SARS-CoV-2, a pandemic, poses a serious health problem for all humanity. Compared with the previous outbreaks of coronavirus infection in 2002 and 2012, COVID-19 infection has high rates of lethality, contagiousness, and comorbidity. The effective methods of prevention and treatment are extremely limited. Oxidative stress is actively involved in the mechanisms of initiation and maintenance of violations of homeostatic reactions in respiratory viral infections. It is important to stop systemic inflammation aimed at "extinguishing" the cytokine "storm", caused by the production of reactive oxygen species. Antioxidant defense medications, such as vitamin C, N-acetylcysteine, melatonin, quercetin, glutathione, astaxanthin, polyphenols, fat-soluble vitamins, and polyunsaturated fatty acids have proven well in experimental and clinical studies of influenza, pneumonia, and other respiratory disorders. The use of medications with antioxidant activity could be justified and most probably would increase the effectiveness of the fight against new coronavirus.

Keywords: Antioxidants, coronaviruses, COVID-19, oxidative stress, pathogenesis, SARS-CoV-2.

Lai C-C, Shih T-P, Ko W-C, Tang H-J, Hsueh P-R. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents 2020; 55(3)105924
[] [PMID: 32081636]
Jin Y, Yang H, Ji W, et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses 2020; 12(4)E372
[] [PMID: 32230900]
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) Outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA 2020; 323(13): 1239-42.
[] [PMID: 32091533]
Mehta MM, Weinberg SE, Chandel NS. Mitochondrial control of immunity: beyond ATP. Nat Rev Immunol 2017; 17(10): 608-20.
[] [PMID: 28669986]
Sies H, Berndt C, Jones DP. Oxidative Stress. Annu Rev Biochem 2017; 86: 715-48.
[] [PMID: 28441057]
Sandhir R, Halder A, Sunkaria A. Mitochondria as a centrally positioned hub in the innate immune response. Biochim Biophys Acta Mol Basis Dis 2017; 1863(5): 1090-7.
[] [PMID: 27794419]
Gonzalez-Gonzalez FJ, Chandel NS, Jain M, Budinger GRS. Reactive oxygen species as signaling molecules in the development of lung fibrosis. Transl Res 2017; 190: 61-8.
[] [PMID: 29080401]
Hosakote YM, Rayavara K. Respiratory syncytial virus-induced oxidative stress in lung pathogenesis Oxidative Stress in Lung Diseases. Singapore: Springer Singapore 2020; pp. 297-330.
Khomich OA, Kochetkov SN, Bartosch B, Ivanov AV. Redox biology of respiratory viral infections. Viruses 2018; 10(8)E392
[] [PMID: 30049972]
Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17(3): 181-92.
[] [PMID: 30531947]
Zarei A, Taghavi Fardood S, Moradnia F, Ramazani AA. Review on coronavirus family persistency and considerations of novel type, COVID-19 features. Eurasian Chemical Communications 2020; 2: 798-811.
Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res 2020; 24: 91-8.
[] [PMID: 32257431]
Ksiazek TG, Erdman D, Goldsmith CS, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003; 348(20): 1953-66.
[] [PMID: 12690092]
de Groot RJ, Baker SC, Baric RS, et al. Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. J Virol 2013; 87(14): 7790-2.
[] [PMID: 23678167]
Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020; 8(5): 475-81.
[] [PMID: 32105632]
Zhou P, Yang X-L, Wang X-G, et al. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. Preprint at BioRxiv 2020.
Phan T. Genetic diversity and evolution of SARS-CoV-2. Infect Genet Evol 2020; 81.
Borges do Nascimento IJ, Cacic N, Abdulazeem HM, et al. Novel coronavirus infection (COVID-19) in humans: A scoping review and meta-analysis. J Clin Med 2020; 9(4)E941
[] [PMID: 32235486]
Wang K, Chen W, Zhou YS, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv 2020.
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181(2): 271-280.e8.
[] [PMID: 32142651]
Ziegler CGK, Allon SJ, Nyquist SK, et al. 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 2020; 181(5): 1016-35.e19.
[] [PMID: 32413319]
Chang Y-S, Ko B-H, Ju J-C, Chang H-H, Huang S-H, Lin C-W. SARS Unique Domain (SUD) of severe acute respiratory syndrome coronavirus induces NLRP3 inflammasome-dependent cxcl10-mediated pulmonary inflammation. Int J Mol Sci 2020; 21(9)E3179
[] [PMID: 32365944]
Zhao C, Zhao W. NLRP3 Inflammasome-a key player in antiviral responses. Front Immunol 2020; 11: 211.
[] [PMID: 32133002]
Chu H, Chan JF-W, Wang Y, et al. Au W-K, Yuen K-Y. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin Infect Dis 2020; 71(6): 1400-9.
[] [PMID: 32270184]
Wang X, Xu W, Hu G, et al. RETRACTED ARTICLE: SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. Cell Mol Immunol 2020.
[] [PMID: 32265513]
Liu K, Chen Y, Lin R, Han K. Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. J Infect 2020; 80(6): e14-8.
[] [PMID: 32171866]
Kubatov AA, Derjabin DG. A new look at the COVID-19 pathogenesis: the disease is a generalized viral vasculitis, and the lung tissue damage is a variant of angiogenic pulmonary edema. Annals of the Russian Academy of Medical Sciences 2020; 75.
Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395(10229): 1033-4.
[] [PMID: 32192578]
Zhang Y, Gao Y, Qiao L, Wang W, Chen D. Inflammatory response cells during acute respiratory distress syndrome in patients with coronavirus disease 2019 (COVID-19). Ann Intern Med 2020; 173(5): 402-4.
[] [PMID: 32282871]
Cao X. COVID-19: immunopathology and its implications for therapy. Nat Rev Immunol 2020; 20(5): 269-70.
[] [PMID: 32273594]
Wang T, Du Z, Zhu F, et al. Comorbidities and multi-organ injuries in the treatment of COVID-19. Lancet 2020; 395(10228)e52
[] [PMID: 32171074]
Sánchez-Rodríguez R, Munari F, Angioni R, et al. Targeting monoamine oxidase to dampen NLRP3 inflammasome activation in inflammation. Cell Mol Immunol 2020. Online ahead of print.
[] [PMID: 32346102]
Delgado-Roche L, Mesta F. Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Arch Med Res 2020; 51(5): 384-7.
[] [PMID: 32402576]
Komaravelli N, Casola A. Respiratory viral infections and subversion of cellular antioxidant defenses. J Pharmacogenomics Pharmacoproteomics 2014; 5(4)1000141
[] [PMID: 25584194]
Miró O, López S, Martínez E, et al. Mitochondrial effects of HIV infection on the peripheral blood mononuclear cells of HIV-infected patients who were never treated with antiretrovirals. Clin Infect Dis 2004; 39(5): 710-6.
[] [PMID: 15356787]
Shao H, Lan D, Duan Z, et al. Upregulation of mitochondrial gene expression in PBMC from convalescent SARS patients. J Clin Immunol 2006; 26(6): 546-54.
[] [PMID: 17024565]
Liu DX, Fung TS, Chong KK, Shukla A, Hilgenfeld R. Accessory proteins of SARS-CoV and other coronaviruses. Antiviral Res 2014; 109: 97-109.
[] [PMID: 24995382]
Wu S, Gao J, Ohlemeyer C, et al. Activation of AP-1 through reactive oxygen species by angiotensin II in rat cardiomyocytes. Free Radic Biol Med 2005; 39(12): 1601-10.
[] [PMID: 16298685]
Li Q, Wang L, Dong C, et al. The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect. J Clin Virol 2005; 34(2): 133-9.
[] [PMID: 16157265]
Imai Y, Kuba K, Neely GG, et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 2008; 133(2): 235-49.
[] [PMID: 18423196]
Lin CW, Lin KH, Hsieh TH, Shiu SY, Li JY. Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis. FEMS Immunol Med Microbiol 2006; 46(3): 375-80.
[] [PMID: 16553810]
Mizutani T, Fukushi S, Saijo M, Kurane I, Morikawa S. Importance of Akt signaling pathway for apoptosis in SARS-CoV-infected Vero E6 cells. Virology 2004; 327(2): 169-74.
[] [PMID: 15351204]
van den Brand JMA, Haagmans BL, van Riel D, Osterhaus ADME, Kuiken T. The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. J Comp Pathol 2014; 151(1): 83-112.
[] [PMID: 24581932]
Smits SL, de Lang A, van den Brand JM, et al. Exacerbated innate host response to SARS-CoV in aged non-human primates. PLoS Pathog 2010; 6(2)e1000756
[] [PMID: 20140198]
Chung HY, Sung B, Jung KJ, Zou Y, Yu BP. The molecular inflammatory process in aging. Antioxid Redox Signal 2006; 8(3-4): 572-81.
[] [PMID: 16677101]
Petrakis D, Margină D, Tsarouhas K, et al. Obesity a risk factor for increased COVID 19 prevalence, severity and lethality. (Review) Mol Med Rep 2020; 22(1): 9-19.
[] [PMID: 32377709]
Kolesnikova LI, Darenskaya MA, Kolesnikov SI. Free radical oxidation: a pathophysiologist’s view. Byulleten Sibirskoy Meditsiny 2017; 16: 16-29.
Kolesnikova LI, Kolesnikov SI, Darenskaya MA, et al. Evaluation of the pro- and antioxidant status of women with HIV or coinfection. Ter Arkh 2016; 88(11): 17-21.
[] [PMID: 28005027]
Chow CW, Herrera Abreu MT, Suzuki T, Downey GP. Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol 2003; 29(4): 427-31.
[] [PMID: 14500253]
Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev 2020; 53: 66-70.
[] [PMID: 32418715]
Kharbat A, Rossettie S, Zumwalt M. Links between exercise/nutrition and antioxidants-protective effects on immune/respiratory systems as defense against viral infections. Southwest Respiratory and Critical Care Chronicles 2020; 8(36): 23-31.
Abouhashem AS, Singh K, Azzazy HME, Sen CK. Is low alveolar type II cell SOD3 in the lungs of elderly linked to the observed severity of COVID-19? Antioxid Redox Signal 2020; 33(2): 59-65.
[] [PMID: 32323565]
Hooper PL. COVID-19 and heme oxygenase: novel insight into the disease and potential therapies. Cell Stress Chaperones 2020; 25(5): 707-10.
[] [PMID: 32500379]
Zabetakis I, Lordan R, Norton C, Tsoupras A. COVID-19: the inflammation link and the role of nutrition in potential mitigation. Nutrients 2020; 12(5)E1466
[] [PMID: 32438620]
Cheng RZ. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)? Medicine in drug discovery 2020; 5: 100028-8.
Calder PC, Carr AC, Gombart AF, Eggersdorfer M. Optimal nutritional status for a well-functioning immune system is an important factor to protect against viral infections. Nutrients 2020; 12(4): 1181.
[] [PMID: 32340216]
Liugan M, Carr AC. Vitamin C and Neutrophil Function: Findings from Randomized Controlled Trials. Nutrients 2019; 11(9)E2102
[] [PMID: 31487891]
Boretti A, Banik BK. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition 2020; 12: 100190-0.
[] [PMID: 32322486]
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(8): 386.
[] [PMID: 32752010]
Hemilä H, Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst Rev 2013; (8): CD005532
[] [PMID: 23925826]
Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013; (1): CD000980
[] [PMID: 23440782]
Hiedra R, Lo KB, Elbashabsheh M, et al. The use of IV vitamin C for patients with COVID-19: a case series. Expert Rev Anti Infect Ther 2020; 18(12): 1259-61.
[] [PMID: 32662690]
Zhang J, Rao X, Li Y, et al. High-dose vitamin C infusion for the treatment of critically ill COVID-19. Research Square 2020.
Waqas Khan HM, Parikh N, Megala SM, Predeteanu GS. Unusual early recovery of a critical COVID-19 patient after administration of intravenous vitamin C. Am J Case Rep 2020; 21: e925521-1.
[] [PMID: 32709838]
Ahmed AK, Albalawi YS, Shora HA, Abdelseed HK, Al-Kattan AN. Effects of quadruple therapy: zinc, quercetin, bromelain and vitamin C on the clinical outcomes of patients infected with COVID-19. Rea Int J of End and Diabe 2020.
Linani A, Benarous K, Yousfi M. Novel structural mechanism of glutathione as a potential peptide inhibitor to the main protease (Mpro): COVID-19 treatment, molecular docking and SAR Study. ChemRxiv 2020.
Roth DE, Richard SA, Black RE. Zinc supplementation for the prevention of acute lower respiratory infection in children in developing countries: meta-analysis and meta-regression of randomized trials. Int J Epidemiol 2010; 39(3): 795-808.
[] [PMID: 20156999]
Wang Q, Yan S-F, Hao Y, Jin S-W. Specialized pro-resolving mediators regulate alveolar fluid clearance during acute respiratory distress syndrome. Chin Med J (Engl) 2018; 131(8): 982-9.
[] [PMID: 29664060]
Sham HP, Walker KH, Abdulnour R-EE, et al. 15-epi-Lipoxin A4, Resolvin D2, and Resolvin D3 induce NF-κB regulators in bacterial pneumonia. J Immunol 2018; 200(8): 2757-66.
[] [PMID: 29523657]
Dushianthan A, Cusack R, Burgess VA, Grocott MPW, Calder PC. Immunonutrition for acute respiratory distress syndrome (ARDS) in adults. Cochrane Database Syst Rev 2019; 1CD012041
[] [PMID: 30677127]
D’Avolio A, Avataneo V, Manca A, et al. 25-Hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2. Nutrients 2020; 12(5): 1359.
[] [PMID: 32397511]
Wimalawansa SJ. COVID-19 might be fought by 2 doses of Vitamin D (200,000-300,000 IU each). Eur J Biomed Pharm Sci 2020; 7: 432-8.
Cui C, Xu P, Li G, et al. Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: Role of renin-angiotensin system. Redox Biol 2019; 26101295
[] [PMID: 31421410]
Teymoori-Rad M, Shokri F, Salimi V, Marashi SM. The interplay between vitamin D and viral infections. Rev Med Virol 2019; 29(2)e2032
[] [PMID: 30614127]
Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiol Infect 2006; 134(6): 1129-40.
[] [PMID: 16959053]
Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients 2015; 7(6): 4240-70.
[] [PMID: 26035247]
Grant WB, Lahore H, McDonnell SL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020; 12(4)E988
[] [PMID: 32252338]
Gombart AF. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol 2009; 4(9): 1151-65.
[] [PMID: 19895218]
Annweiler G, Corvaisier M, Gautier J, et al. Vitamin D supplementation associated to better survival in hospitalized frail elderly COVID-19 patients: The GERIA-COVID quasi-Experimental Study. Nutrients 2020; 12(11): 3377.
[] [PMID: 33147894]
Annweiler C, Hanotte B, Grandin de l’Eprevier C, Sabatier JM, Lafaie L, Célarier T. Vitamin D and survival in COVID-19 patients: A quasi-experimental study. J Steroid Biochem Mol Biol 2020; 204105771
[] [PMID: 33065275]
Tan CW, Ho LP, Kalimuddin S, et al. Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19). Nutrition 2020; 79-80111017
[] [PMID: 33039952]
Rastogi A, Bhansali A, Khare N, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study). Postgrad Med J 2020; 3.
[] [PMID: 33184146]
Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, et al. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. J Steroid Biochem Mol Biol 2020; 203105751
[] [PMID: 32871238]
Meydani SN, Leka LS, Fine BC, et al. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA 2004; 292(7): 828-36.
[] [PMID: 15315997]
De la Fuente M, Hernanz A, Guayerbas N, Victor VM, Arnalich F. Vitamin E ingestion improves several immune functions in elderly men and women. Free Radic Res 2008; 42(3): 272-80.
[] [PMID: 18344122]
Zhang Y, Ding S, Li C, Wang Y, Chen Z, Wang Z. Effects of N-acetylcysteine treatment in acute respiratory distress syndrome: A meta-analysis. Exp Ther Med 2017; 14(4): 2863-8.
[] [PMID: 28928799]
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(10): 1.
de Alencar JCG, Moreira CDL, Müller AD, et al. Double-blind, randomized, placebo-controlled trial with n-acetylcysteine for treatment of severe acute respiratory syndrome caused by coronavirus disease 2019 (COVID-19). Clin Infect Dis 2020.ciaa1443
[] [PMID: 32964918]
Jo S, Kim S, Shin DH, Kim M-S. Inhibition of SARS-CoV 3CL protease by flavonoids. J Enzyme Inhib Med Chem 2020; 35(1): 145-51.
[] [PMID: 31724441]
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 2020; 9(8): 659.
[] [PMID: 32722164]
Mani JS, Johnson JB, Steel JC, et al. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res 2020; 284: 197989-9.
[] [PMID: 32360300]
Wu G. Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health. Amino Acids 2020; 52(3): 329-60.
[] [PMID: 32072297]
Shneider A, Kudriavtsev A, Vakhrusheva A. Can melatonin reduce the severity of COVID-19 pandemic? Int Rev Immunol 2020; 39(4): 153-62.
[] [PMID: 32347747]
Yang M. Cell pyroptosis, a potential pathogenic mechanism of 2019-nCoV infection In: SSRN. 2020; pp. 1-7.
Adikwu E, Brambaifa N, Obianime WA. Melatonin and alpha lipoic acid restore electrolytes and kidney morphology of lopinavir/ritonavir-treated rats. J Nephropharmacol 2019; 9e06
Madaeva IM, Danusevich IN, Zhambalova RM, Kolesnikova LI. Melatonin in therapy of sleep disorders age-related estrogen deficiency. Zh Nevrol Psikhiatr Im S S Korsakova 2017; 117(5): 81-4.
[] [PMID: 28638037]
Costa JAV, Moreira JB, Fanka LS, da Costa Kosinski R, de Morais MG. Microalgal biotechnology applied in biomedicine. Handbook of Algal Science, Technology and Medicine 429-39.
Talukdar J, Dasgupta S, Nagle V, Bhadra B. COVID-19: Potential of microalgae derived natural astaxanthin as adjunctive supplement in alleviating cytokine storm. 2020. Available from:
Hamidi Alamdari D, Bagheri Moghaddam A, Amini S, Hamidi Alamdari A, Damsaz M, Yarahmadi A. The application of a reduced dye used in orthopedics as a novel treatment against coronavirus (COVID-19): A suggested therapeutic protocol. Arch Bone Jt Surg 2020; 8(Suppl. 1): 291-4.
[] [PMID: 32607398]
Alamdari DH, Moghaddam AB, Amini S, et al. Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial. Eur J Pharmacol 2020; 885173494
[] [PMID: 32828741]
Butler MJ, Barrientos RM. The impact of nutrition on COVID-19 susceptibility and long-term consequences. Brain Behav Immun 2020; 87: 53-4.
[] [PMID: 32311498]

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