RNA viruses induce cellular oxidative stress and antioxidants reduce the generation of viral particles, both in vitro and in vivo
DOI:
https://doi.org/10.18041/2322-8415/ingelibre.2020.v8n18.7168Keywords:
IRES choranovirus, NF-κB, ROS, oxidative stress, redox balance, PPARγAbstract
During infection by RNA viruses, intracellular oxidative mechanisms such as reactive oxygen species (ROS) and pro-oxidant cytokines are generated. RNA viruses require the presence of redox molecules in the cell membrane to make the necessary conformational changes for cell attachment and penetration. In addition, they need to induce cellular oxidative stress since this allows the expression of the biochemical machinery necessary for their translation using internal ribosome entry sites (IRES). The generation of ROS, as a consequence of viral infection or by xenobiotic agents, stimulates the activation of the NF-κB pathway and, together with oxidative activity, increases viral replication. Likewise, RNA viruses inhibit antioxidant enzymes such as superoxide dismutase and important factors in anti-inflammatory pathways such as Nrf2, PPARγ, among others. The treatment and use of antioxidants as therapeutic agents in viral diseases, both in animals and in human patients, affects the folding of viruses during binding to receptors and decreases the generation of virions per cell, thus allowing the sustained production of viral antigens to develop efficient and balanced immunity.
Downloads
Download data is not yet available.
References
1. Reshi ML, Su Y-C, Hong J-R. RNA viruses: ROS-mediated cell death. Int J Cell Biol. 2014;2014.
2. Zhang Z, Rong L, Li Y-P. Flaviviridae viruses and oxidative stress: implications for viral pathogenesis. Oxid Med Cell Longev. 2019;2019.
3. Camini FC, da Silva Caetano CC, Almeida LT, de Brito Magalhaes CL. Implications of oxidative stress on viral pathogenesis. Arch Virol. 2017;162(4):907–17.
4. Liu M, Chen F, Liu T, Chen F, Liu S, Yang J. The role of oxidative stress in influenza virus infection. Microbes Infect. 2017;19(12):580–6.
5. Ivanov A V, Valuev-Elliston VT, Ivanova ON, Kochetkov SN, Starodubova ES, Bartosch B, et al. Oxidative stress during HIV infection: mechanisms and consequences. Oxid Med Cell Longev. 2016;2016.
6. Rebbani K, Tsukiyama-Kohara K. HCV-induced oxidative stress: battlefield-winning strategy. Oxid Med Cell Longev. 2016;2016.
7. Buccigrossi V, Laudiero G, Russo C, Miele E, Sofia M, Monini M, et al. Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes. PLoS One. 2014;9(6):e99830.
8. Delgado-Roche L, Mesta F. Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Arch Med Res. 2020;
9. Suhail S, Zajac J, Fossum C, Lowater H, McCracken C, Severson N, et al. Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review. Protein J. 2020;1–13.
10. Hyodo K, Hashimoto K, Kuchitsu K, Suzuki N, Okuno T. Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus. Proc Natl Acad Sci. 2017;114(7):E1282–90.
11. Guerrero CA, Acosta O. Inflammatory and oxidative stress in rotavirus infection. World J Virol. 2016;5(2):38.
12. Khomich OA, Kochetkov SN, Bartosch B, Ivanov A V. Redox biology of respiratory viral infections. Viruses. 2018;10(8):392.
13. Beck MA, Levander OA. Dietary oxidative stress and the potentiation of viral infection. Annu Rev Nutr. 1998;18(1):93–116.
14. Beck MA, Handy J, Levander OA. The role of oxidative stress in viral infections. Ann N Y Acad Sci. 2000;917(1):906–12.
15. Almond MH, Edwards MR, Barclay WS, Johnston SL. Obesity and susceptibility to severe outcomes following respiratory viral infection. Thorax. 2013;68(7):684–6.
16. Honce R, Schultz-Cherry S. Impact of obesity on influenza A virus pathogenesis, immune response, and evolution. Front Immunol. 2019;10:1071.
17. Gowdy KM, Krantz QT, King C, Boykin E, Jaspers I, Linak WP, et al. Role of oxidative stress on diesel-enhanced influenza infection in mice. Part Fibre Toxicol. 2010;7(1):34.
18. Nakagawa K, Lokugamage KG, Makino S. Viral and cellular mRNA translation in coronavirus-infected cells. In: Advances in virus research. Elsevier; 2016. p. 165–92.
19. Hakim M, Fass D. Cytosolic disulfide bond formation in cells infected with large nucleocytoplasmic DNA viruses. Antioxid Redox Signal. 2010;13(8):1261–71.
20. Kojer K, Riemer J. Balancing oxidative protein folding: the influences of reducing pathways on disulfide bond formation. Biochim Biophys Acta (BBA)-Proteins Proteomics. 2014;1844(8):1383–90.
21. Schmitz ML, Kracht M, Saul V V. The intricate interplay between RNA viruses and NF-κB. Biochim Biophys Acta (BBA)-Molecular Cell Res. 2014;1843(11):2754–64.
22. Struzik J, Szulc-Dąbrowska L. Manipulation of non-canonical NF-κB signaling by non-oncogenic viruses. Arch Immunol Ther Exp (Warsz). 2019;67(1):41–8.
23. Guererero CA, Murillo A, Acosta O. Inhibition of rotavirus infection in cultured cells by N-acetyl-cysteine, PPARγ agonists and NSAIDs. Antiviral Res. 2012;96(1):1–12.
24. Gómez D, Muñoz N, Guerrero R, Acosta O, Guerrero CA. PPARγ agonists as an anti-inflammatory treatment inhibiting rotavirus infection of small intestinal villi. PPAR Res. 2016;2016.
25. Guerrero CA, Paula Pardo VR, Rafael Guerrero OA. Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors. Mem Inst Oswaldo Cruz. 2013;108(6):741–54.
26. Guerrero CA, Torres DP, García LL, Guerrero RA, Acosta O. N‐Acetylcysteine Treatment of Rotavirus‐Associated Diarrhea in Children. Pharmacother J Hum Pharmacol Drug Ther. 2014;34(11):e333–40.
27. Marino-Merlo F, Papaianni E, Medici MA, Macchi B, Grelli S, Mosca C, et al. HSV-1-induced activation of NF-κ B protects U937 monocytic cells against both virus replication and apoptosis. Cell Death Dis. 2016;7(9):e2354–e2354.
28. Tai D, Tsai S, Chen Y, Chuang Y, Peng C, Sheen I, et al. Activation of nuclear factor κB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis. Hepatology. 2000;31(3):656–64.
29. Paracha UZ, Fatima K, Alqahtani M, Chaudhary A, Abuzenadah A, Damanhouri G, et al. Oxidative stress and hepatitis C virus. Virol J. 2013;10(1):1–9.
30. Brady G, Bowie AG. Innate immune activation of NFκB and its antagonism by poxviruses. Cytokine Growth Factor Rev. 2014;25(5):611–20.
31. Huang J, Hume AJ, Abo KM, Werder RB, Villacorta-Martin C, Alysandratos K-D, et al. SARS-CoV-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response. Cell Stem Cell. 2020;
32. Lauxmann MA, Santucci NE, Autrán-Gómez AM. The SARS-CoV-2 coronavirus and the COVID-19 outbreak. Int braz j urol. 2020;46:6–18.
33. Shimizu Y, Hendershot LM. Oxidative folding: cellular strategies for dealing with the resultant equimolar production of reactive oxygen species. Antioxid Redox Signal. 2009;11(9):2317–31.
34. Huang J, Schneider RJ. Adenovirus inhibition of cellular protein synthesis involves inactivation of cap-binding protein. Cell. 1991;65(2):271–80.
35. Yang D, Halaby MJ, Zhang Y. The identification of an internal ribosomal entry site in the 5′-untranslated region of p53 mRNA provides a novel mechanism for the regulation of its translation following DNA damage. Oncogene. 2006;25(33):4613–9.
36. Lee Y-H, Lai C-L, Hsieh S-H, Shieh C-C, Huang L-M, Wu-Hsieh BA. Influenza A virus induction of oxidative stress and MMP-9 is associated with severe lung pathology in a mouse model. Virus Res. 2013;178(2):411–22.
37. Godet A-C, David F, Hantelys F, Tatin F, Lacazette E, Garmy-Susini B, et al. IRES trans-acting factors, key actors of the stress response. Int J Mol Sci. 2019;20(4):924.
38. Gendron K, Ferbeyre G, Heveker N, Brakier-Gingras L. The activity of the HIV-1 IRES is stimulated by oxidative stress and controlled by a negative regulatory element. Nucleic Acids Res. 2011;39(3):902–12.
39. Ghosh A, Shcherbik N. Effects of Oxidative Stress on Protein Translation: Implications for Cardiovascular Diseases. Int J Mol Sci. 2020;21(8):2661.
40. Lindquist S. Varying patterns of protein synthesis in Drosophila during heat shock: implications for regulation. Dev Biol. 1980;77(2):463–79.
41. Bonneau AM, Sonenberg N. Involvement of the 24-kDa cap-binding protein in regulation of protein synthesis in mitosis. J Biol Chem. 1987;262(23):11134–9.
42. Holcik M, Lefebvre C, Yeh C, Chow T, Korneluk RG. A new internal-ribosome-entry-site motif potentiates XIAP-mediated cytoprotection. Nat Cell Biol. 1999;1(3):190–2.
43. Coldwell MJ, Mitchell SA, Stoneley M, MacFarlane M, Willis AE. Initiation of Apaf-1 translation by internal ribosome entry. Oncogene. 2000;19(7):899–905.
44. Ray PS, Grover R, Das S. Two internal ribosome entry sites mediate the translation of p53 isoforms. EMBO Rep. 2006;7(4):404–10.
45. Stoneley M, Chappell SA, Jopling CL, Dickens M, MacFarlane M, Willis AE. c-Myc protein synthesis is initiated from the internal ribosome entry segment during apoptosis. Mol Cell Biol. 2000;20(4):1162–9.
46. Vagner S, Gensac M-C, Maret A, Bayard F, Amalric F, Prats H, et al. Alternative translation of human fibroblast growth factor 2 mRNA occurs by internal entry of ribosomes. Mol Cell Biol. 1995;15(1):35–44.
47. Morfoisse F, Tatin F, Hantelys F, Adoue A, Helfer A-C, Cassant-Sourdy S, et al. Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis. Cancer Res. 2016;76(15):4394–405.
48. Reddy PVB, Agudelo M, Atluri VSR, Nair MP. Inhibition of nuclear factor erythroid 2-related factor 2 exacerbates HIV-1 gp120-induced oxidative and inflammatory response: role in HIV associated neurocognitive disorder. Neurochem Res. 2012;37(8):1697–706.
49. Kalinowska M, Bazdar DA, Lederman MM, Funderburg N, Sieg SF. Decreased IL-7 responsiveness is related to oxidative stress in HIV disease. PLoS One. 2013;8(3):e58764.
50. Hagen TM, Huang S, Curnutte J, Fowler P, Martinez V, Wehr CM, et al. Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma. Proc Natl Acad Sci. 1994;91(26):12808–12.
51. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005;5(3):215–29.
52. Lee C. Therapeutic modulation of virus-induced oxidative stress via the Nrf2-dependent antioxidative pathway. Oxid Med Cell Longev. 2018;2018.
53. Garofalo RP, Kolli D, Casola A. Respiratory syncytial virus infection: mechanisms of redox control and novel therapeutic opportunities. Antioxid Redox Signal. 2013;18(2):186–217.
54. Cho H-Y, Imani F, Miller-DeGraff L, Walters D, Melendi GA, Yamamoto M, et al. Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease. Am J Respir Crit Care Med. 2009;179(2):138–50.
55. Chen X, Ren F, Hesketh J, Shi X, Li J, Gan F, et al. Reactive oxygen species regulate the replication of porcine circovirus type 2 via NF-κB pathway. Virology. 2012;426(1):66–72.
56. Ruggieri A, Anticoli S, Nencioni L, Sgarbanti R, Garaci E, Palamara AT. Interplay between hepatitis C virus and redox cell signaling. Int J Mol Sci. 2013;14(3):4705–21.
57. Jang SK, Kräusslich HG, Nicklin MJ, Duke GM, Palmenberg AC, Wimmer E. A segment of the 5’nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J Virol. 1988;62(8):2636–43.
58. Pelletier J, Sonenberg N. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature. 1988;334(6180):320–5.
59. Mokrejš M, Vopálenský V, Kolenatý O, Mašek T, Feketová Z, Sekyrová P, et al. IRESite: the database of experimentally verified IRES structures (www. iresite. org). Nucleic Acids Res. 2006;34(suppl_1):D125–30.
60. Balvay L, Lastra ML, Sargueil B, Darlix J-L, Ohlmann T. Translational control of retroviruses. Nat Rev Microbiol. 2007;5(2):128–40.
61. Berlioz C, Darlix J-L. An internal ribosomal entry mechanism promotes translation of murine leukemia virus gag polyprotein precursors. J Virol. 1995;69(4):2214–22.
62. Jackson RJ. The current status of vertebrate cellular mRNA IRESs. Cold Spring Harb Perspect Biol. 2013;5(2):a011569.
63. Kwan T, Thompson SR. Noncanonical translation initiation in eukaryotes. Cold Spring Harb Perspect Biol. 2019;11(4):a032672.
64. Wang C, Sarnow P, Siddiqui A. Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism. J Virol. 1993;67(6):3338–44.
65. Créancier L, Morello D, Mercier P, Prats A-C. Fibroblast growth factor 2 internal ribosome entry site (IRES) activity ex vivo and in transgenic mice reveals a stringent tissue-specific regulation. J Cell Biol. 2000;150(1):275–81.
66. Ji B, Harris BRE, Liu Y, Deng Y, Gradilone SA, Cleary MP, et al. Targeting IRES-mediated p53 synthesis for cancer diagnosis and therapeutics. Int J Mol Sci. 2017;18(1):93.
67. Griffiths A, Coen DM. An unusual internal ribosome entry site in the herpes simplex virus thymidine kinase gene. Proc Natl Acad Sci. 2005;102(27):9667–72.
68. Yu Y, Alwine JC. 19S late mRNAs of simian virus 40 have an internal ribosome entry site upstream of the virion structural protein 3 coding sequence. J Virol. 2006;80(13):6553–8.
69. Coleman HM, Brierley I, Stevenson PG. An internal ribosome entry site directs translation of the murine gammaherpesvirus 68 MK3 open reading frame. J Virol. 2003;77(24):13093–105.
70. Bieleski L, Talbot SJ. Kaposi’s sarcoma-associated herpesvirus vCyclin open reading frame contains an internal ribosome entry site. J Virol. 2001;75(4):1864–9.
71. Tahiri-Alaoui A, Smith LP, Baigent S, Kgosana L, Petherbridge LJ, Lambeth LS, et al. Identification of an intercistronic internal ribosome entry site in a Marek’s disease virus immediate-early gene. J Virol. 2009;83(11):5846–53.
72. Chan S-W. Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation. J Gen Virol. 2016;97(9):2301.
73. Gac M, Bigda J, Vahlenkamp TW. Increased mitochondrial superoxide dismutase expression and lowered production of reactive oxygen species during rotavirus infection. Virology. 2010;404(2):293–303.
74. Gjyshi O, Bottero V, Veettil MV, Dutta S, Singh VV, Chikoti L, et al. Kaposi’s sarcoma-associated herpesvirus induces Nrf2 during de novo infection of endothelial cells to create a microenvironment conducive to infection. PLoS Pathog. 2014;10(10):e1004460.
75. Hosakote YM, Jantzi PD, Esham DL, Spratt H, Kurosky A, Casola A, et al. Viral-mediated inhibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med. 2011;183(11):1550–60.
76. Stehbens WE. Oxidative stress in viral hepatitis and AIDS. Exp Mol Pathol. 2004;77(2):121–32.
77. Choi J, James Ou J-H. Mechanisms of liver injury. III. Oxidative stress in the pathogenesis of hepatitis C virus. Am J Physiol Liver Physiol. 2006;290(5):G847–51.
78. Price TO, Ercal N, Nakaoke R, Banks WA. HIV-1 viral proteins gp120 and Tat induce oxidative stress in brain endothelial cells. Brain Res. 2005;1045(1–2):57–63.
79. Olagnier D, Peri S, Steel C, van Montfoort N, Chiang C, Beljanski V, et al. Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells. PLoS Pathog. 2014;10(12):e1004566.
80. Jiang Y, Scofield VL, Yan M, Qiang W, Liu N, Reid AJ, et al. Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by antioxidant treatment with a refined monosodium α-luminol (Galavit). J Virol. 2006;80(9):4557–69.
81. Fukuyama S, Kawaoka Y. The pathogenesis of influenza virus infections: the contributions of virus and host factors. Curr Opin Immunol. 2011;23(4):481–6.
82. Santoro MG, Rossi A, Amici C. NF‐κB and virus infection: who controls whom. EMBO J. 2003;22(11):2552–60.
83. Cecchini R, Cecchini AL. SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Med Hypotheses. 2020;143:110102.
84. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet (London, England). 2020;395(10229):1033.
85. Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T, van Loo G, 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.
86. Muralidharan S, Mandrekar P. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol. 2013;94(6):1167–84.
87. Chen Y, Zhou Z, Min W. Mitochondria, oxidative stress and innate immunity. Front Physiol. 2018;9:1487.
88. Poe FL, Corn J. N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2. Med Hypotheses. 2020;109862.
89. Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr H-W, et al. 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;79(3):413–20.
90. Narayanan A, Amaya M, Voss K, Chung M, Benedict A, Sampey G, et al. Reactive oxygen species activate NFκB (p65) and p53 and induce apoptosis in RVFV infected liver cells. Virology. 2014;449:270–86.
91. Kim HJ, Kim C-H, Ryu J-H, Kim M-J, Park CY, Lee JM, et al. Reactive oxygen species induce antiviral innate immune response through IFN-λ regulation in human nasal epithelial cells. Am J Respir Cell Mol Biol. 2013;49(5):855–65.
92. Casola A, Burger N, Liu T, Jamaluddin M, Brasier AR, Garofalo RP. Oxidant tone regulates RANTES gene expression in airway epithelial cells infected with respiratory syncytial virus Role in viral-induced interferon regulatory factor activation. J Biol Chem. 2001;276(23):19715–22.
93. Liu B, Fang M, He Z, Cui D, Jia S, Lin X, et al. Hepatitis B virus stimulates G6PD expression through HBx-mediated Nrf2 activation. Cell Death Dis. 2015;6(11):e1980–e1980.
94. Kosmider B, Messier EM, Janssen WJ, Nahreini P, Wang J, Hartshorn KL, et al. Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus. Respir Res. 2012;13(1):43.
95. Kharazmi A, Nielsen H, Schiøtz PO. N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism. Int J Immunopharmacol. 1988;10(1):39–46.
96. Huang S, Zhu B, Cheon IS, Goplen NP, Jiang L, Zhang R, et al. PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection. J Virol. 2019;93(9).
97. Knipe B, Potula R, Ramirez SH. Peroxisome proliferator-activated receptor-gamma activation suppresses HIV-1 replication in an animal model of encephalitis. 2008;
98. Gopal R, Mendy A, Marinelli MA, Richwalls LJ, Seger PJ, Patel S, et al. Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection. Viruses. 2019;11(6):505.
99. Arnold R, Neumann M, König W. Peroxisome proliferator‐activated receptor‐γ agonists inhibit respiratory syncytial virus‐induced expression of intercellular adhesion molecule‐1 in human lung epithelial cells. Immunology. 2007;121(1):71–81.
100. Belvisi MG, Hele DJ, Birrell MA. Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation. Eur J Pharmacol. 2006;533(1–3):101–9.
101. Ciavarella C, Motta I, Valente S, Pasquinelli G. Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease. Molecules. 2020;25(9):2076.
102. Genolet R, Wahli W, Michalik L. PPARs as drug targets to modulate inflammatory responses? Curr Drug Targets-Inflammation Allergy. 2004;3(4):361–75.
103. Clark RB. The role of PPARs in inflammation and immunity. J Leukoc Biol. 2002;71(3):388–400.
104. Qi C, Zhu Y, Reddy JK. Peroxisome proliferator-activated receptors, coactivators, and downstream targets. Cell Biochem Biophys. 2000;32(1–3):187.
105. Leopold Wager CM, Arnett E, Schlesinger LS. Macrophage nuclear receptors: Emerging key players in infectious diseases. PLoS Pathog. 2019;15(3):e1007585.
106. Yeligar SM, Ward JM, Harris FL, Brown LAS, Guidot DM, Cribbs SK. Dysregulation of Alveolar Macrophage PPARγ, NADPH Oxidases, and TGFβ1 in Otherwise Healthy HIV-Infected Individuals. AIDS Res Hum Retroviruses. 2017;33(10):1018–26.
107. Villapol S. Roles of peroxisome proliferator-activated receptor gamma on brain and peripheral inflammation. Cell Mol Neurobiol. 2018;38(1):121–32.
108. Martin H. Role of PPAR-gamma in inflammation. Prospects for therapeutic intervention by food components. Mutat Res Mol Mech Mutagen. 2010;690(1–2):57–63.
109. Sozio MS, Lu C, Zeng Y, Liangpunsakul S, Crabb DW. Activated AMPK inhibits PPAR-α and PPAR-γ transcriptional activity in hepatoma cells. Am J Physiol Liver Physiol. 2011;301(4):G739–47.
110. Sreekanth GP, Panaampon J, Suttitheptumrong A, Chuncharunee A, Bootkunha J, Yenchitsomanus P, et al. Drug repurposing of N-acetyl cysteine as antiviral against dengue virus infection. Antiviral Res. 2019;166:42–55.
111. 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 e IF 2α kinase PKR. Cell Microbiol. 2015;17(9):1391–404.
112. Chen N, Warner JL, Reiss CS. NSAID treatment suppresses VSV propagation in mouse CNS. Virology. 2000;276(1):44–51.
113. 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(5):548–55.
114. Bellavite P, Donzelli A. Hesperidin and SARS-CoV-2: New Light on the Healthy Function of Citrus Fruits. Antioxidants (Basel) 2020 Aug 13; 9 (8).
115. Singh J, Dhindsa RS, Misra V, Singh B. SARS-CoV2 infectivity is potentially modulated by host redox status. Comput Struct Biotechnol J. 2020;18:3705–11.
116. Guthappa R. Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine. 2020;
117. Nasi A, McArdle S, Gaudernack G, Westman G, Melief C, Rockberg J, et al. 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 reports. 2020;7:768–71.
118. DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C, et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014;88(2):913–24.
119. Fan X, Staitieh BS, Jensen JS, Mould KJ, Greenberg JA, Joshi PC, et al. Activating the Nrf2-mediated antioxidant response element restores barrier function in the alveolar epithelium of HIV-1 transgenic rats. Am J Physiol Cell Mol Physiol. 2013;305(3):L267–77.
120. Bai Z, Zhao X, Li C, Sheng C, Li H. EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells. Gut Pathog. 2020;12:1–12.
121. Komaravelli N, Ansar M, Garofalo RP, Casola A. Respiratory syncytial virus induces NRF2 degradation through a promyelocytic leukemia protein‐ring finger protein 4 dependent pathway. Free Radic Biol Med. 2017;113:494–504.
122. Deramaudt TB, Dill C, Bonay M. Regulation of oxidative stress by Nrf2 in the pathophysiology of infectious diseases. Médecine Mal Infect. 2013;43(3):100–7.
123. Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2(1):1–9.
124. Kim JH, Gupta SC, Park B, Yadav VR, Aggarwal BB. Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)‐κB and NF‐κB‐regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis. Mol Nutr Food Res. 2012;56(3):454–65.
125. Checconi P, De Angelis M, Marcocci ME, Fraternale A, Magnani M, Palamara AT, et al. Redox-Modulating Agents in the Treatment of Viral Infections. Int J Mol Sci. 2020;21(11):4084.
126. Cantin AM, North SL, Hubbard RC, Crystal RG. Normal alveolar epithelial lining fluid contains high levels of glutathione. J Appl Physiol. 1987;63(1):152–7.
127. Winterbourn CC, Hampton MB. Thiol chemistry and specificity in redox signaling. Free Radic Biol Med. 2008;45(5):549–61.
128. Patra U, Mukhopadhyay U, Mukherjee A, Sarkar R, Chawla-Sarkar M. Progressive Rotavirus Infection Downregulates Redox-Sensitive Transcription Factor Nrf2 and Nrf2-Driven Transcription Units. Oxid Med Cell Longev. 2020;2020.
129. 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 reports. 2020;101063.
130. Zhong M, Sun A, Xiao T, Yao G, Sang L, Zheng X, et al. A Randomized, Single-blind, Group sequential, Active-controlled Study to evaluate the clinical efficacy and safety of α-Lipoic acid for critically ill patients with coronavirus disease 2019 (COVID-19). medRxiv. 2020;
131. Wang Y, Zhao S, Chen Y, Wang Y, Wang T, Wo X, et al. N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication and inflammatory response. Antiviral Res. 2020;179:104699.
132. Shi Z, Puyo CA. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther Clin Risk Manag. 2020;16:1047.
133. HO W-Z, DOUGLAS SD. Glutathione and N-acetylcysteine suppression of human immunodeficiency virus replication in human monocyte/macrophages in vitro. AIDS Res Hum Retroviruses. 1992;8(7):1249–53.
134. Jorge-Aarón R-M, Rosa-Ester M-P. N-acetylcysteine as a potential treatment for COVID-19. Future Medicine; 2020.
135. Sadowska AM, Manuel-y-Keenoy B, Vertongen T, Schippers G, Radomska-Lesniewska D, Heytens E, et al. Effect of N-acetylcysteine on neutrophil activation markers in healthy volunteers: in vivo and in vitro study. Pharmacol Res. 2006;53(3):216–25.
136. Liu Y, Luo G, Qian X, Wu C, Tang Y, Chen B, et al. Experience of N-acetylcysteine airway management in the successful treatment of one case of critical condition with COVID-19. 2020;
137. Ibrahim H, Perl A, Smith D, Lewis T, Kon Z, Goldenberg R, et al. Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine. Clin Immunol. 2020;219:108544.
138. Codo AC, Davanzo GG, Monteiro LB, Souza G, Muraro S, Carregari V, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis dependent axis. 2020;
139. Calderon MN, Guerrero CA, Acosta O, Lopez S, Arias CF. Inhibiting rotavirus infection by membrane-impermeant thiol/disulfide exchange blockers and antibodies against protein disulfide isomerase. Intervirology. 2012;55(6):451–64.
140. Rivera M, Guerrero CA, Acosta O. Thiol/disulfide exchange occurs in rotavirus structural proteins during contact with intestinal villus cell surface. Acta Virol. 2020;64(1):44–58.
141. Bhattacharyay S, Hati S. Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor. bioRxiv. 2020;
142. 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(10):13185–93.
143. Hendrickson RG. What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose? Clin Toxicol. 2019;57(8):686–91.
2. Zhang Z, Rong L, Li Y-P. Flaviviridae viruses and oxidative stress: implications for viral pathogenesis. Oxid Med Cell Longev. 2019;2019.
3. Camini FC, da Silva Caetano CC, Almeida LT, de Brito Magalhaes CL. Implications of oxidative stress on viral pathogenesis. Arch Virol. 2017;162(4):907–17.
4. Liu M, Chen F, Liu T, Chen F, Liu S, Yang J. The role of oxidative stress in influenza virus infection. Microbes Infect. 2017;19(12):580–6.
5. Ivanov A V, Valuev-Elliston VT, Ivanova ON, Kochetkov SN, Starodubova ES, Bartosch B, et al. Oxidative stress during HIV infection: mechanisms and consequences. Oxid Med Cell Longev. 2016;2016.
6. Rebbani K, Tsukiyama-Kohara K. HCV-induced oxidative stress: battlefield-winning strategy. Oxid Med Cell Longev. 2016;2016.
7. Buccigrossi V, Laudiero G, Russo C, Miele E, Sofia M, Monini M, et al. Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes. PLoS One. 2014;9(6):e99830.
8. Delgado-Roche L, Mesta F. Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Arch Med Res. 2020;
9. Suhail S, Zajac J, Fossum C, Lowater H, McCracken C, Severson N, et al. Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review. Protein J. 2020;1–13.
10. Hyodo K, Hashimoto K, Kuchitsu K, Suzuki N, Okuno T. Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus. Proc Natl Acad Sci. 2017;114(7):E1282–90.
11. Guerrero CA, Acosta O. Inflammatory and oxidative stress in rotavirus infection. World J Virol. 2016;5(2):38.
12. Khomich OA, Kochetkov SN, Bartosch B, Ivanov A V. Redox biology of respiratory viral infections. Viruses. 2018;10(8):392.
13. Beck MA, Levander OA. Dietary oxidative stress and the potentiation of viral infection. Annu Rev Nutr. 1998;18(1):93–116.
14. Beck MA, Handy J, Levander OA. The role of oxidative stress in viral infections. Ann N Y Acad Sci. 2000;917(1):906–12.
15. Almond MH, Edwards MR, Barclay WS, Johnston SL. Obesity and susceptibility to severe outcomes following respiratory viral infection. Thorax. 2013;68(7):684–6.
16. Honce R, Schultz-Cherry S. Impact of obesity on influenza A virus pathogenesis, immune response, and evolution. Front Immunol. 2019;10:1071.
17. Gowdy KM, Krantz QT, King C, Boykin E, Jaspers I, Linak WP, et al. Role of oxidative stress on diesel-enhanced influenza infection in mice. Part Fibre Toxicol. 2010;7(1):34.
18. Nakagawa K, Lokugamage KG, Makino S. Viral and cellular mRNA translation in coronavirus-infected cells. In: Advances in virus research. Elsevier; 2016. p. 165–92.
19. Hakim M, Fass D. Cytosolic disulfide bond formation in cells infected with large nucleocytoplasmic DNA viruses. Antioxid Redox Signal. 2010;13(8):1261–71.
20. Kojer K, Riemer J. Balancing oxidative protein folding: the influences of reducing pathways on disulfide bond formation. Biochim Biophys Acta (BBA)-Proteins Proteomics. 2014;1844(8):1383–90.
21. Schmitz ML, Kracht M, Saul V V. The intricate interplay between RNA viruses and NF-κB. Biochim Biophys Acta (BBA)-Molecular Cell Res. 2014;1843(11):2754–64.
22. Struzik J, Szulc-Dąbrowska L. Manipulation of non-canonical NF-κB signaling by non-oncogenic viruses. Arch Immunol Ther Exp (Warsz). 2019;67(1):41–8.
23. Guererero CA, Murillo A, Acosta O. Inhibition of rotavirus infection in cultured cells by N-acetyl-cysteine, PPARγ agonists and NSAIDs. Antiviral Res. 2012;96(1):1–12.
24. Gómez D, Muñoz N, Guerrero R, Acosta O, Guerrero CA. PPARγ agonists as an anti-inflammatory treatment inhibiting rotavirus infection of small intestinal villi. PPAR Res. 2016;2016.
25. Guerrero CA, Paula Pardo VR, Rafael Guerrero OA. Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine, peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2 inhibitors. Mem Inst Oswaldo Cruz. 2013;108(6):741–54.
26. Guerrero CA, Torres DP, García LL, Guerrero RA, Acosta O. N‐Acetylcysteine Treatment of Rotavirus‐Associated Diarrhea in Children. Pharmacother J Hum Pharmacol Drug Ther. 2014;34(11):e333–40.
27. Marino-Merlo F, Papaianni E, Medici MA, Macchi B, Grelli S, Mosca C, et al. HSV-1-induced activation of NF-κ B protects U937 monocytic cells against both virus replication and apoptosis. Cell Death Dis. 2016;7(9):e2354–e2354.
28. Tai D, Tsai S, Chen Y, Chuang Y, Peng C, Sheen I, et al. Activation of nuclear factor κB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis. Hepatology. 2000;31(3):656–64.
29. Paracha UZ, Fatima K, Alqahtani M, Chaudhary A, Abuzenadah A, Damanhouri G, et al. Oxidative stress and hepatitis C virus. Virol J. 2013;10(1):1–9.
30. Brady G, Bowie AG. Innate immune activation of NFκB and its antagonism by poxviruses. Cytokine Growth Factor Rev. 2014;25(5):611–20.
31. Huang J, Hume AJ, Abo KM, Werder RB, Villacorta-Martin C, Alysandratos K-D, et al. SARS-CoV-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response. Cell Stem Cell. 2020;
32. Lauxmann MA, Santucci NE, Autrán-Gómez AM. The SARS-CoV-2 coronavirus and the COVID-19 outbreak. Int braz j urol. 2020;46:6–18.
33. Shimizu Y, Hendershot LM. Oxidative folding: cellular strategies for dealing with the resultant equimolar production of reactive oxygen species. Antioxid Redox Signal. 2009;11(9):2317–31.
34. Huang J, Schneider RJ. Adenovirus inhibition of cellular protein synthesis involves inactivation of cap-binding protein. Cell. 1991;65(2):271–80.
35. Yang D, Halaby MJ, Zhang Y. The identification of an internal ribosomal entry site in the 5′-untranslated region of p53 mRNA provides a novel mechanism for the regulation of its translation following DNA damage. Oncogene. 2006;25(33):4613–9.
36. Lee Y-H, Lai C-L, Hsieh S-H, Shieh C-C, Huang L-M, Wu-Hsieh BA. Influenza A virus induction of oxidative stress and MMP-9 is associated with severe lung pathology in a mouse model. Virus Res. 2013;178(2):411–22.
37. Godet A-C, David F, Hantelys F, Tatin F, Lacazette E, Garmy-Susini B, et al. IRES trans-acting factors, key actors of the stress response. Int J Mol Sci. 2019;20(4):924.
38. Gendron K, Ferbeyre G, Heveker N, Brakier-Gingras L. The activity of the HIV-1 IRES is stimulated by oxidative stress and controlled by a negative regulatory element. Nucleic Acids Res. 2011;39(3):902–12.
39. Ghosh A, Shcherbik N. Effects of Oxidative Stress on Protein Translation: Implications for Cardiovascular Diseases. Int J Mol Sci. 2020;21(8):2661.
40. Lindquist S. Varying patterns of protein synthesis in Drosophila during heat shock: implications for regulation. Dev Biol. 1980;77(2):463–79.
41. Bonneau AM, Sonenberg N. Involvement of the 24-kDa cap-binding protein in regulation of protein synthesis in mitosis. J Biol Chem. 1987;262(23):11134–9.
42. Holcik M, Lefebvre C, Yeh C, Chow T, Korneluk RG. A new internal-ribosome-entry-site motif potentiates XIAP-mediated cytoprotection. Nat Cell Biol. 1999;1(3):190–2.
43. Coldwell MJ, Mitchell SA, Stoneley M, MacFarlane M, Willis AE. Initiation of Apaf-1 translation by internal ribosome entry. Oncogene. 2000;19(7):899–905.
44. Ray PS, Grover R, Das S. Two internal ribosome entry sites mediate the translation of p53 isoforms. EMBO Rep. 2006;7(4):404–10.
45. Stoneley M, Chappell SA, Jopling CL, Dickens M, MacFarlane M, Willis AE. c-Myc protein synthesis is initiated from the internal ribosome entry segment during apoptosis. Mol Cell Biol. 2000;20(4):1162–9.
46. Vagner S, Gensac M-C, Maret A, Bayard F, Amalric F, Prats H, et al. Alternative translation of human fibroblast growth factor 2 mRNA occurs by internal entry of ribosomes. Mol Cell Biol. 1995;15(1):35–44.
47. Morfoisse F, Tatin F, Hantelys F, Adoue A, Helfer A-C, Cassant-Sourdy S, et al. Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis. Cancer Res. 2016;76(15):4394–405.
48. Reddy PVB, Agudelo M, Atluri VSR, Nair MP. Inhibition of nuclear factor erythroid 2-related factor 2 exacerbates HIV-1 gp120-induced oxidative and inflammatory response: role in HIV associated neurocognitive disorder. Neurochem Res. 2012;37(8):1697–706.
49. Kalinowska M, Bazdar DA, Lederman MM, Funderburg N, Sieg SF. Decreased IL-7 responsiveness is related to oxidative stress in HIV disease. PLoS One. 2013;8(3):e58764.
50. Hagen TM, Huang S, Curnutte J, Fowler P, Martinez V, Wehr CM, et al. Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma. Proc Natl Acad Sci. 1994;91(26):12808–12.
51. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005;5(3):215–29.
52. Lee C. Therapeutic modulation of virus-induced oxidative stress via the Nrf2-dependent antioxidative pathway. Oxid Med Cell Longev. 2018;2018.
53. Garofalo RP, Kolli D, Casola A. Respiratory syncytial virus infection: mechanisms of redox control and novel therapeutic opportunities. Antioxid Redox Signal. 2013;18(2):186–217.
54. Cho H-Y, Imani F, Miller-DeGraff L, Walters D, Melendi GA, Yamamoto M, et al. Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease. Am J Respir Crit Care Med. 2009;179(2):138–50.
55. Chen X, Ren F, Hesketh J, Shi X, Li J, Gan F, et al. Reactive oxygen species regulate the replication of porcine circovirus type 2 via NF-κB pathway. Virology. 2012;426(1):66–72.
56. Ruggieri A, Anticoli S, Nencioni L, Sgarbanti R, Garaci E, Palamara AT. Interplay between hepatitis C virus and redox cell signaling. Int J Mol Sci. 2013;14(3):4705–21.
57. Jang SK, Kräusslich HG, Nicklin MJ, Duke GM, Palmenberg AC, Wimmer E. A segment of the 5’nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J Virol. 1988;62(8):2636–43.
58. Pelletier J, Sonenberg N. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature. 1988;334(6180):320–5.
59. Mokrejš M, Vopálenský V, Kolenatý O, Mašek T, Feketová Z, Sekyrová P, et al. IRESite: the database of experimentally verified IRES structures (www. iresite. org). Nucleic Acids Res. 2006;34(suppl_1):D125–30.
60. Balvay L, Lastra ML, Sargueil B, Darlix J-L, Ohlmann T. Translational control of retroviruses. Nat Rev Microbiol. 2007;5(2):128–40.
61. Berlioz C, Darlix J-L. An internal ribosomal entry mechanism promotes translation of murine leukemia virus gag polyprotein precursors. J Virol. 1995;69(4):2214–22.
62. Jackson RJ. The current status of vertebrate cellular mRNA IRESs. Cold Spring Harb Perspect Biol. 2013;5(2):a011569.
63. Kwan T, Thompson SR. Noncanonical translation initiation in eukaryotes. Cold Spring Harb Perspect Biol. 2019;11(4):a032672.
64. Wang C, Sarnow P, Siddiqui A. Translation of human hepatitis C virus RNA in cultured cells is mediated by an internal ribosome-binding mechanism. J Virol. 1993;67(6):3338–44.
65. Créancier L, Morello D, Mercier P, Prats A-C. Fibroblast growth factor 2 internal ribosome entry site (IRES) activity ex vivo and in transgenic mice reveals a stringent tissue-specific regulation. J Cell Biol. 2000;150(1):275–81.
66. Ji B, Harris BRE, Liu Y, Deng Y, Gradilone SA, Cleary MP, et al. Targeting IRES-mediated p53 synthesis for cancer diagnosis and therapeutics. Int J Mol Sci. 2017;18(1):93.
67. Griffiths A, Coen DM. An unusual internal ribosome entry site in the herpes simplex virus thymidine kinase gene. Proc Natl Acad Sci. 2005;102(27):9667–72.
68. Yu Y, Alwine JC. 19S late mRNAs of simian virus 40 have an internal ribosome entry site upstream of the virion structural protein 3 coding sequence. J Virol. 2006;80(13):6553–8.
69. Coleman HM, Brierley I, Stevenson PG. An internal ribosome entry site directs translation of the murine gammaherpesvirus 68 MK3 open reading frame. J Virol. 2003;77(24):13093–105.
70. Bieleski L, Talbot SJ. Kaposi’s sarcoma-associated herpesvirus vCyclin open reading frame contains an internal ribosome entry site. J Virol. 2001;75(4):1864–9.
71. Tahiri-Alaoui A, Smith LP, Baigent S, Kgosana L, Petherbridge LJ, Lambeth LS, et al. Identification of an intercistronic internal ribosome entry site in a Marek’s disease virus immediate-early gene. J Virol. 2009;83(11):5846–53.
72. Chan S-W. Hydrogen peroxide induces La cytoplasmic shuttling and increases hepatitis C virus internal ribosome entry site-dependent translation. J Gen Virol. 2016;97(9):2301.
73. Gac M, Bigda J, Vahlenkamp TW. Increased mitochondrial superoxide dismutase expression and lowered production of reactive oxygen species during rotavirus infection. Virology. 2010;404(2):293–303.
74. Gjyshi O, Bottero V, Veettil MV, Dutta S, Singh VV, Chikoti L, et al. Kaposi’s sarcoma-associated herpesvirus induces Nrf2 during de novo infection of endothelial cells to create a microenvironment conducive to infection. PLoS Pathog. 2014;10(10):e1004460.
75. Hosakote YM, Jantzi PD, Esham DL, Spratt H, Kurosky A, Casola A, et al. Viral-mediated inhibition of antioxidant enzymes contributes to the pathogenesis of severe respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med. 2011;183(11):1550–60.
76. Stehbens WE. Oxidative stress in viral hepatitis and AIDS. Exp Mol Pathol. 2004;77(2):121–32.
77. Choi J, James Ou J-H. Mechanisms of liver injury. III. Oxidative stress in the pathogenesis of hepatitis C virus. Am J Physiol Liver Physiol. 2006;290(5):G847–51.
78. Price TO, Ercal N, Nakaoke R, Banks WA. HIV-1 viral proteins gp120 and Tat induce oxidative stress in brain endothelial cells. Brain Res. 2005;1045(1–2):57–63.
79. Olagnier D, Peri S, Steel C, van Montfoort N, Chiang C, Beljanski V, et al. Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells. PLoS Pathog. 2014;10(12):e1004566.
80. Jiang Y, Scofield VL, Yan M, Qiang W, Liu N, Reid AJ, et al. Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by antioxidant treatment with a refined monosodium α-luminol (Galavit). J Virol. 2006;80(9):4557–69.
81. Fukuyama S, Kawaoka Y. The pathogenesis of influenza virus infections: the contributions of virus and host factors. Curr Opin Immunol. 2011;23(4):481–6.
82. Santoro MG, Rossi A, Amici C. NF‐κB and virus infection: who controls whom. EMBO J. 2003;22(11):2552–60.
83. Cecchini R, Cecchini AL. SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Med Hypotheses. 2020;143:110102.
84. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet (London, England). 2020;395(10229):1033.
85. Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T, van Loo G, 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.
86. Muralidharan S, Mandrekar P. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol. 2013;94(6):1167–84.
87. Chen Y, Zhou Z, Min W. Mitochondria, oxidative stress and innate immunity. Front Physiol. 2018;9:1487.
88. Poe FL, Corn J. N-Acetylcysteine: a potential therapeutic agent for SARS-CoV-2. Med Hypotheses. 2020;109862.
89. Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr H-W, et al. 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;79(3):413–20.
90. Narayanan A, Amaya M, Voss K, Chung M, Benedict A, Sampey G, et al. Reactive oxygen species activate NFκB (p65) and p53 and induce apoptosis in RVFV infected liver cells. Virology. 2014;449:270–86.
91. Kim HJ, Kim C-H, Ryu J-H, Kim M-J, Park CY, Lee JM, et al. Reactive oxygen species induce antiviral innate immune response through IFN-λ regulation in human nasal epithelial cells. Am J Respir Cell Mol Biol. 2013;49(5):855–65.
92. Casola A, Burger N, Liu T, Jamaluddin M, Brasier AR, Garofalo RP. Oxidant tone regulates RANTES gene expression in airway epithelial cells infected with respiratory syncytial virus Role in viral-induced interferon regulatory factor activation. J Biol Chem. 2001;276(23):19715–22.
93. Liu B, Fang M, He Z, Cui D, Jia S, Lin X, et al. Hepatitis B virus stimulates G6PD expression through HBx-mediated Nrf2 activation. Cell Death Dis. 2015;6(11):e1980–e1980.
94. Kosmider B, Messier EM, Janssen WJ, Nahreini P, Wang J, Hartshorn KL, et al. Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus. Respir Res. 2012;13(1):43.
95. Kharazmi A, Nielsen H, Schiøtz PO. N-acetylcysteine inhibits human neutrophil and monocyte chemotaxis and oxidative metabolism. Int J Immunopharmacol. 1988;10(1):39–46.
96. Huang S, Zhu B, Cheon IS, Goplen NP, Jiang L, Zhang R, et al. PPAR-γ in macrophages limits pulmonary inflammation and promotes host recovery following respiratory viral infection. J Virol. 2019;93(9).
97. Knipe B, Potula R, Ramirez SH. Peroxisome proliferator-activated receptor-gamma activation suppresses HIV-1 replication in an animal model of encephalitis. 2008;
98. Gopal R, Mendy A, Marinelli MA, Richwalls LJ, Seger PJ, Patel S, et al. Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Suppresses Inflammation and Bacterial Clearance during Influenza-Bacterial Super-Infection. Viruses. 2019;11(6):505.
99. Arnold R, Neumann M, König W. Peroxisome proliferator‐activated receptor‐γ agonists inhibit respiratory syncytial virus‐induced expression of intercellular adhesion molecule‐1 in human lung epithelial cells. Immunology. 2007;121(1):71–81.
100. Belvisi MG, Hele DJ, Birrell MA. Peroxisome proliferator-activated receptor gamma agonists as therapy for chronic airway inflammation. Eur J Pharmacol. 2006;533(1–3):101–9.
101. Ciavarella C, Motta I, Valente S, Pasquinelli G. Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease. Molecules. 2020;25(9):2076.
102. Genolet R, Wahli W, Michalik L. PPARs as drug targets to modulate inflammatory responses? Curr Drug Targets-Inflammation Allergy. 2004;3(4):361–75.
103. Clark RB. The role of PPARs in inflammation and immunity. J Leukoc Biol. 2002;71(3):388–400.
104. Qi C, Zhu Y, Reddy JK. Peroxisome proliferator-activated receptors, coactivators, and downstream targets. Cell Biochem Biophys. 2000;32(1–3):187.
105. Leopold Wager CM, Arnett E, Schlesinger LS. Macrophage nuclear receptors: Emerging key players in infectious diseases. PLoS Pathog. 2019;15(3):e1007585.
106. Yeligar SM, Ward JM, Harris FL, Brown LAS, Guidot DM, Cribbs SK. Dysregulation of Alveolar Macrophage PPARγ, NADPH Oxidases, and TGFβ1 in Otherwise Healthy HIV-Infected Individuals. AIDS Res Hum Retroviruses. 2017;33(10):1018–26.
107. Villapol S. Roles of peroxisome proliferator-activated receptor gamma on brain and peripheral inflammation. Cell Mol Neurobiol. 2018;38(1):121–32.
108. Martin H. Role of PPAR-gamma in inflammation. Prospects for therapeutic intervention by food components. Mutat Res Mol Mech Mutagen. 2010;690(1–2):57–63.
109. Sozio MS, Lu C, Zeng Y, Liangpunsakul S, Crabb DW. Activated AMPK inhibits PPAR-α and PPAR-γ transcriptional activity in hepatoma cells. Am J Physiol Liver Physiol. 2011;301(4):G739–47.
110. Sreekanth GP, Panaampon J, Suttitheptumrong A, Chuncharunee A, Bootkunha J, Yenchitsomanus P, et al. Drug repurposing of N-acetyl cysteine as antiviral against dengue virus infection. Antiviral Res. 2019;166:42–55.
111. 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 e IF 2α kinase PKR. Cell Microbiol. 2015;17(9):1391–404.
112. Chen N, Warner JL, Reiss CS. NSAID treatment suppresses VSV propagation in mouse CNS. Virology. 2000;276(1):44–51.
113. 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(5):548–55.
114. Bellavite P, Donzelli A. Hesperidin and SARS-CoV-2: New Light on the Healthy Function of Citrus Fruits. Antioxidants (Basel) 2020 Aug 13; 9 (8).
115. Singh J, Dhindsa RS, Misra V, Singh B. SARS-CoV2 infectivity is potentially modulated by host redox status. Comput Struct Biotechnol J. 2020;18:3705–11.
116. Guthappa R. Molecular Docking Studies of N-Acetyl Cysteine, Zinc Acetyl Cysteine and Niclosamide on SARS Cov 2 Protease and Its Comparison with Hydroxychloroquine. 2020;
117. Nasi A, McArdle S, Gaudernack G, Westman G, Melief C, Rockberg J, et al. 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 reports. 2020;7:768–71.
118. DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C, et al. Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 2014;88(2):913–24.
119. Fan X, Staitieh BS, Jensen JS, Mould KJ, Greenberg JA, Joshi PC, et al. Activating the Nrf2-mediated antioxidant response element restores barrier function in the alveolar epithelium of HIV-1 transgenic rats. Am J Physiol Cell Mol Physiol. 2013;305(3):L267–77.
120. Bai Z, Zhao X, Li C, Sheng C, Li H. EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells. Gut Pathog. 2020;12:1–12.
121. Komaravelli N, Ansar M, Garofalo RP, Casola A. Respiratory syncytial virus induces NRF2 degradation through a promyelocytic leukemia protein‐ring finger protein 4 dependent pathway. Free Radic Biol Med. 2017;113:494–504.
122. Deramaudt TB, Dill C, Bonay M. Regulation of oxidative stress by Nrf2 in the pathophysiology of infectious diseases. Médecine Mal Infect. 2013;43(3):100–7.
123. Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2(1):1–9.
124. Kim JH, Gupta SC, Park B, Yadav VR, Aggarwal BB. Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)‐κB and NF‐κB‐regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis. Mol Nutr Food Res. 2012;56(3):454–65.
125. Checconi P, De Angelis M, Marcocci ME, Fraternale A, Magnani M, Palamara AT, et al. Redox-Modulating Agents in the Treatment of Viral Infections. Int J Mol Sci. 2020;21(11):4084.
126. Cantin AM, North SL, Hubbard RC, Crystal RG. Normal alveolar epithelial lining fluid contains high levels of glutathione. J Appl Physiol. 1987;63(1):152–7.
127. Winterbourn CC, Hampton MB. Thiol chemistry and specificity in redox signaling. Free Radic Biol Med. 2008;45(5):549–61.
128. Patra U, Mukhopadhyay U, Mukherjee A, Sarkar R, Chawla-Sarkar M. Progressive Rotavirus Infection Downregulates Redox-Sensitive Transcription Factor Nrf2 and Nrf2-Driven Transcription Units. Oxid Med Cell Longev. 2020;2020.
129. 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 reports. 2020;101063.
130. Zhong M, Sun A, Xiao T, Yao G, Sang L, Zheng X, et al. A Randomized, Single-blind, Group sequential, Active-controlled Study to evaluate the clinical efficacy and safety of α-Lipoic acid for critically ill patients with coronavirus disease 2019 (COVID-19). medRxiv. 2020;
131. Wang Y, Zhao S, Chen Y, Wang Y, Wang T, Wo X, et al. N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication and inflammatory response. Antiviral Res. 2020;179:104699.
132. Shi Z, Puyo CA. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Ther Clin Risk Manag. 2020;16:1047.
133. HO W-Z, DOUGLAS SD. Glutathione and N-acetylcysteine suppression of human immunodeficiency virus replication in human monocyte/macrophages in vitro. AIDS Res Hum Retroviruses. 1992;8(7):1249–53.
134. Jorge-Aarón R-M, Rosa-Ester M-P. N-acetylcysteine as a potential treatment for COVID-19. Future Medicine; 2020.
135. Sadowska AM, Manuel-y-Keenoy B, Vertongen T, Schippers G, Radomska-Lesniewska D, Heytens E, et al. Effect of N-acetylcysteine on neutrophil activation markers in healthy volunteers: in vivo and in vitro study. Pharmacol Res. 2006;53(3):216–25.
136. Liu Y, Luo G, Qian X, Wu C, Tang Y, Chen B, et al. Experience of N-acetylcysteine airway management in the successful treatment of one case of critical condition with COVID-19. 2020;
137. Ibrahim H, Perl A, Smith D, Lewis T, Kon Z, Goldenberg R, et al. Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine. Clin Immunol. 2020;219:108544.
138. Codo AC, Davanzo GG, Monteiro LB, Souza G, Muraro S, Carregari V, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis dependent axis. 2020;
139. Calderon MN, Guerrero CA, Acosta O, Lopez S, Arias CF. Inhibiting rotavirus infection by membrane-impermeant thiol/disulfide exchange blockers and antibodies against protein disulfide isomerase. Intervirology. 2012;55(6):451–64.
140. Rivera M, Guerrero CA, Acosta O. Thiol/disulfide exchange occurs in rotavirus structural proteins during contact with intestinal villus cell surface. Acta Virol. 2020;64(1):44–58.
141. Bhattacharyay S, Hati S. Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor. bioRxiv. 2020;
142. 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(10):13185–93.
143. Hendrickson RG. What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose? Clin Toxicol. 2019;57(8):686–91.
Downloads
Published
2020-11-30
