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The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death

Xie et al., Cellular & Molecular Biology Letters, doi:10.1186/s11658-024-00659-6
Nov 2024  
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Vitamin C for COVID-19
6th treatment shown to reduce risk in September 2020, now with p = 0.00000002 from 73 studies, recognized in 12 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
Review of the effects of reactive oxygen species (ROS) on cell death pathways in SARS-CoV-2 infection. SARS-CoV-2 induces oxidative stress and ROS generation which can lead to several types of regulated cell death including NETosis, ferroptosis, apoptosis, pyroptosis, necroptosis, and autophagy. Authors discuss the mechanisms by which ROS promotes each of these cell death pathways. Potential ROS-related therapies for COVID-19 are explored, including NET inhibitors like sivelestat and dornase alpha, the IL-6 receptor antagonist tocilizumab, iron chelators like deferoxamine and deferiprone to inhibit ferroptosis, glutathione and N-acetylcysteine as antioxidants, vitamins C and E, selenium to induce ferroptosis-inhibiting glutathione peroxidase 4, and melatonin as an antioxidant and myeloperoxidase inhibitor. Several ongoing clinical trials are evaluating these ROS-related therapeutic strategies.
Reviews covering vitamin C for COVID-19 include1-15.
Review covers vitamin C, melatonin, N-acetylcysteine, selenium, HCQ, and apremilast.
Xie et al., 8 Nov 2024, peer-reviewed, 8 authors. Contact: pengtaojiao66@126.com, liuv@henau.edu.cn.
This PaperVitamin CAll
The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death
Jiufeng Xie, Cui Yuan, Sen Yang, Zhenling Ma, Wenqing Li, Lin Mao, Pengtao Jiao, Wei Liu
Cellular & Molecular Biology Letters, doi:10.1186/s11658-024-00659-6
Coronavirus disease 2019 (COVID-19) represents the novel respiratory infectious disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by rapid spread throughout the world. Reactive oxygen species (ROS) account for cellular metabolic by-products, and excessive ROS accumulation can induce oxidative stress due to insufficient endogenous antioxidant ability. In the case of oxidative stress, ROS production exceeds the cellular antioxidant capacity, thus leading to cell death. SARS-CoV-2 can activate different cell death pathways in the context of infection in host cells, such as neutrophil extracellular trap (NET) osis, ferroptosis, apoptosis, pyroptosis, necroptosis and autophagy, which are closely related to ROS signalling and control. In this review, we comprehensively elucidated the relationship between ROS generation and the death of host cells after SARS-CoV-2 infection, which leads to the development of COVID-19, aiming to provide a reasonable basis for the existing interventions and further development of novel therapies against SARS-CoV-2.
Author contributions W.L. and J.X. wrote the manuscript. Y.C. and W.L. drew the figures and designed the table. S.Y. and P.J. revised the manuscript and figures. Z.M., L.M. and W.L. provided conceptual ideas and revised the manuscript. All the authors have read and approved the final manuscript. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Respir Med Case Rep. 2020;30: 101063.', 'journal-title': 'Respir Med Case Rep'}, { 'issue': '1', 'key': '659_CR106', 'doi-asserted-by': 'publisher', 'first-page': '5279', 'DOI': '10.1080/21655979.2021.1964158', 'volume': '12', 'author': 'F Han', 'year': '2021', 'unstructured': 'Han F, Li S, Yang Y, Bai Z. Interleukin-6 promotes ferroptosis in ' 'bronchial epithelial cells by inducing reactive oxygen species-dependent ' 'lipid peroxidation and disrupting iron homeostasis. Bioengineered. ' '2021;12(1):5279–88.', 'journal-title': 'Bioengineered'}, { 'issue': '4', 'key': '659_CR107', 'doi-asserted-by': 'publisher', 'first-page': '691', 'DOI': '10.1007/s00262-018-2120-5', 'volume': '67', 'author': 'MJ Scheffel', 'year': '2018', 'unstructured': 'Scheffel MJ, Scurti G, Wyatt MM. N-acetyl cysteine protects ' 'anti-melanoma cytotoxic T cells from exhaustion induced by rapid ' 'expansion via the downmodulation of Foxo1 in an Akt-dependent manner. 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Cell. 2020;181(5):1036-1045.e9.', 'journal-title': 'Cell'}, { 'issue': '8', 'key': '659_CR114', 'doi-asserted-by': 'publisher', 'first-page': '3131', 'DOI': '10.3390/nu5083131', 'volume': '5', 'author': 'BM Mohammed', 'year': '2013', 'unstructured': 'Mohammed BM, Fisher BJ, Kraskauskas D, Farkas D, Brophy DF, Fowler AA ' '3rd, et\xa0al. Vitamin C: a novel regulator of neutrophil extracellular ' 'trap formation. Nutrients. 2013;5(8):3131–51.', 'journal-title': 'Nutrients'}, { 'issue': '6', 'key': '659_CR115', 'doi-asserted-by': 'publisher', 'first-page': '1297', 'DOI': '10.1093/ajcn/nqaa095', 'volume': '111', 'author': 'J Zhang', 'year': '2020', 'unstructured': '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(6):1297–9.', 'journal-title': 'Am J Clin Nutr'}, { 'key': '659_CR116', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.mehy.2020.109878', 'volume': '143', 'author': 'M Kieliszek', 'year': '2020', 'unstructured': 'Kieliszek M, Lipinski B. Selenium supplementation in the prevention of ' 'coronavirus infections (COVID-19). Med Hypotheses. 2020;143: 109878.', 'journal-title': 'Med Hypotheses'}, { 'issue': '5', 'key': '659_CR117', 'doi-asserted-by': 'publisher', 'first-page': '1262', 'DOI': '10.1016/j.cell.2019.03.032', 'volume': '177', 'author': 'I Alim', 'year': '2019', 'unstructured': 'Alim I, Caulfield JT, Chen Y, Swarup V, Geschwind DH, Ivanova E, et\xa0' 'al. Selenium drives a transcriptional adaptive program to block ' 'ferroptosis and treat stroke. Cell. 2019;177(5):1262-1279.e25.', 'journal-title': 'Cell'}, { 'key': '659_CR118', 'doi-asserted-by': 'publisher', 'first-page': '1024', 'DOI': '10.1016/j.freeradbiomed.2015.10.398', 'volume': '89', 'author': 'H Björnsdottir', 'year': '2015', 'unstructured': 'Björnsdottir H, Welin A, Michaëlsson E, Osla V, Berg S, Christenson K, ' 'et\xa0al. Neutrophil NET formation is regulated from the inside by ' 'myeloperoxidase-processed reactive oxygen species. Free Radic Biol Med. ' '2015;89:1024–35.', 'journal-title': 'Free Radic Biol Med'}, { 'key': '659_CR119', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jinorgbio.2021.111546', 'volume': '223', 'author': 'OG Camp', 'year': '2021', 'unstructured': 'Camp OG, Bai D, Gonullu DC, Nayak N, Abu-Soud HM. Melatonin interferes ' 'with COVID-19 at several distinct ROS-related steps. J Inorg Biochem. 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Exp ' 'Parasitol. 2014;147:72–80.', 'journal-title': 'Exp Parasitol.'}, { 'issue': '22', 'key': '659_CR122', 'doi-asserted-by': 'publisher', 'first-page': '10499', 'DOI': '10.18632/aging.102472', 'volume': '11', 'author': 'Y Zhang', 'year': '2019', 'unstructured': 'Zhang Y, He F, Chen Z, Su Q, Yan M, Zhang Q, et\xa0al. Melatonin ' 'modulates IL-1β-induced extracellular matrix remodeling in human nucleus ' 'pulposus cells and attenuates rat intervertebral disc degeneration and ' 'inflammation. Aging (Albany NY). 2019;11(22):10499–512.', 'journal-title': 'Aging (Albany NY)'}, { 'issue': '1', 'key': '659_CR123', 'doi-asserted-by': 'publisher', 'first-page': '81', 'DOI': '10.1186/s11658-024-00602-9', 'volume': '29', 'author': 'LY Zheng', 'year': '2024', 'unstructured': 'Zheng LY, Duan Y, He PY, Wu MY, Wei ST, Du XH, et\xa0al. Dysregulated ' 'dendritic cells in sepsis: functional impairment and regulated cell ' 'death. Cell Mol Biol Lett. 2024;29(1):81.', 'journal-title': 'Cell Mol Biol Lett.'}], 'container-title': 'Cellular &amp; Molecular Biology Letters', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1186/s11658-024-00659-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1186/s11658-024-00659-6/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1186/s11658-024-00659-6.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 11, 8]], 'date-time': '2024-11-08T23:01:13Z', 'timestamp': 1731106873000}, 'score': 1, 'resource': {'primary': {'URL': 'https://cmbl.biomedcentral.com/articles/10.1186/s11658-024-00659-6'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 11, 8]]}, 'references-count': 123, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2024, 12]]}}, 'alternative-id': ['659'], 'URL': 'http://dx.doi.org/10.1186/s11658-024-00659-6', 'relation': {}, 'ISSN': ['1689-1392'], 'subject': [], 'container-title-short': 'Cell Mol Biol Lett', 'published': {'date-parts': [[2024, 11, 8]]}, 'assertion': [ { 'value': '13 May 2024', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '24 October 2024', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '8 November 2024', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'Not applicable.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}, { 'value': 'Not applicable.', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Consent for publication'}}, { 'value': 'The authors declare that they have no competing interests.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '138'}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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