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The role of cell death in SARS-CoV-2 infection

Yuan et al., Signal Transduction and Targeted Therapy, doi:10.1038/s41392-023-01580-8
Sep 2023  
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14th treatment shown to reduce risk in February 2021
 
*, now with p = 0.000027 from 24 studies, recognized in 3 countries.
Lower risk for mortality, hospitalization, and cases.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
Review of cell death pathways in SARS-CoV-2 infection. Authors note that N-acetylcysteine (NAC) is a precursor to glutathione that may inhibit ferroptosis. Ferroptosis is a regulated cell death triggered by oxidative stress that has been implicated in COVID-19 pathogenesis. Through replenishing glutathione stores and reinforcing the glutathione peroxidase-4 pathway, NAC is suggested to potentially ameliorate ferroptosis in COVID-19.
See Schloss et al. for another review covering N-acetylcysteine for COVID-19.
Review covers selenium and N-acetylcysteine.
Yuan et al., 20 Sep 2023, peer-reviewed, 10 authors. Contact: liuv@henau.edu.cn.
This PaperN-acetylcys..All
The role of cell death in SARS-CoV-2 infection
Cui Yuan, Zhenling Ma, Jiufeng Xie, Wenqing Li, Lijuan Su, Guozhi Zhang, Jun Xu, Yaru Wu, Min Zhang, Wei Liu
Signal Transduction and Targeted Therapy, doi:10.1038/s41392-023-01580-8
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed coronavirus disease 2019 (COVID-19). COVID-19 cases often experience acute respiratory distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death in infected cells. Cell death mechanisms have a vital role in maintaining a suitable environment to achieve normal cell functionality. Nonetheless, these processes are dysregulated, potentially contributing to disease pathogenesis. Over the past decades, multiple cell death pathways are becoming better understood. Growing evidence suggests that the induction of cell death by the coronavirus may significantly contributes to viral infection and pathogenicity. However, the interaction of SARS-CoV-2 with cell death, together with its associated mechanisms, is yet to be elucidated. In this review, we summarize the existing evidence concerning the molecular modulation of cell death in SARS-CoV-2 infection as well as viral-host interactions, which may shed new light on antiviral therapy against SARS-CoV-2.
AUTHOR CONTRIBUTIONS C.Y. and W.L. wrote the manuscript and created the figures. W.L. and Z.M. revised the manuscript and figures. J.X., W.L., L.S., G.Z., X.J., Y.W., and M.Z. provided conceptual ideas and revised the manuscript. All the authors have read and approved the final manuscript. ADDITIONAL INFORMATION Competing interests: The authors declare no competing interests. Figures were created with biorender.com.
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COVID-19 cases often experience acute respiratory distress syndrome, ' 'which has caused millions of deaths. Apart from triggering inflammatory and immune responses, ' 'many viral infections can cause programmed cell death in infected cells. Cell death ' 'mechanisms have a vital role in maintaining a suitable environment to achieve normal cell ' 'functionality. Nonetheless, these processes are dysregulated, potentially contributing to ' 'disease pathogenesis. Over the past decades, multiple cell death pathways are becoming better ' 'understood. Growing evidence suggests that the induction of cell death by the coronavirus may ' 'significantly contributes to viral infection and pathogenicity. However, the interaction of ' 'SARS-CoV-2 with cell death, together with its associated mechanisms, is yet to be elucidated. ' 'In this review, we summarize the existing evidence concerning the molecular modulation of ' 'cell death in SARS-CoV-2 infection as well as viral-host interactions, which may shed new ' 'light on antiviral therapy against SARS-CoV-2.</jats:p>', 'DOI': '10.1038/s41392-023-01580-8', 'type': 'journal-article', 'created': {'date-parts': [[2023, 9, 20]], 'date-time': '2023-09-20T00:02:11Z', 'timestamp': 1695168131000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'The role of cell death in SARS-CoV-2 infection', 'prefix': '10.1038', 'volume': '8', 'author': [ {'given': 'Cui', 'family': 'Yuan', 'sequence': 'first', 'affiliation': []}, {'given': 'Zhenling', 'family': 'Ma', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jiufeng', 'family': 'Xie', 'sequence': 'additional', 'affiliation': []}, {'given': 'Wenqing', 'family': 'Li', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lijuan', 'family': 'Su', 'sequence': 'additional', 'affiliation': []}, {'given': 'Guozhi', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jun', 'family': 'Xu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yaru', 'family': 'Wu', 'sequence': 'additional', 'affiliation': []}, {'given': 'Min', 'family': 'Zhang', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-0004-2713', 'authenticated-orcid': False, 'given': 'Wei', 'family': 'Liu', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2023, 9, 20]]}, 'reference': [ { 'key': '1580_CR1', 'doi-asserted-by': 'publisher', 'first-page': '355', 'DOI': '10.1038/s41577-020-0331-4', 'volume': '20', 'author': 'M Merad', 'year': '2020', 'unstructured': 'Merad, M. & Martin, J. 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B'}, { 'key': '1580_CR172', 'doi-asserted-by': 'publisher', 'first-page': '107209', 'DOI': '10.1016/j.intimp.2020.107209', 'volume': '90', 'author': 'V Maldonado', 'year': '2021', 'unstructured': 'Maldonado, V. et al. Pentoxifylline decreases serum LDH levels and ' 'increases lymphocyte count in COVID-19 patients: results from an ' 'external pilot study. Int. Immunopharmacol. 90, 107209 (2021).', 'journal-title': 'Int. Immunopharmacol.'}, { 'key': '1580_CR173', 'doi-asserted-by': 'publisher', 'DOI': '10.1186/s12967-022-03363-1', 'volume': '20', 'author': 'Y Liu', 'year': '2022', 'unstructured': 'Liu, Y. et al. The role of neutrophil elastase in aortic valve ' 'calcification. J. Transl. Med. 20, 167 (2022).', 'journal-title': 'J. Transl. Med.'}, { 'key': '1580_CR174', 'doi-asserted-by': 'publisher', 'first-page': '73', 'DOI': '10.1038/s41421-021-00310-0', 'volume': '7', 'author': 'H Ma', 'year': '2021', 'unstructured': 'Ma, H. et al. Pyroptosis of syncytia formed by fusion of SARS-CoV-2 ' 'spike and ACE2-expressing cells. Cell Discov. 7, 73 (2021).', 'journal-title': 'Cell Discov.'}, { 'key': '1580_CR175', 'doi-asserted-by': 'publisher', 'first-page': 'eabf8577', 'DOI': '10.1126/sciadv.abf8577', 'volume': '7', 'author': 'H Chu', 'year': '2021', 'unstructured': 'Chu, H. et al. Targeting highly pathogenic coronavirus-induced apoptosis ' 'reduces viral pathogenesis and disease severity. Sci. Adv. 7, eabf8577 ' '(2021).', 'journal-title': 'Sci. Adv.'}, { 'key': '1580_CR176', 'first-page': '3419', 'volume': '39', 'author': 'N Lobo-Galo', 'year': '2021', 'unstructured': 'Lobo-Galo, N., Terrazas-López, M., Martínez-Martínez, A. & Díaz-Sánchez, ' 'Á. G. FDA-approved thiol-reacting drugs that potentially bind into the ' 'SARS-CoV-2 main protease, essential for viral replication. J. Biomol. ' 'Struct. Dyn. 39, 3419–3427 (2021).', 'journal-title': 'J. Biomol. Struct. Dyn.'}], 'container-title': 'Signal Transduction and Targeted Therapy', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41392-023-01580-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41392-023-01580-8', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41392-023-01580-8.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 9, 20]], 'date-time': '2023-09-20T00:02:26Z', 'timestamp': 1695168146000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41392-023-01580-8'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 9, 20]]}, 'references-count': 176, 'journal-issue': {'issue': '1', 'published-online': {'date-parts': [[2023, 12]]}}, 'alternative-id': ['1580'], 'URL': 'http://dx.doi.org/10.1038/s41392-023-01580-8', 'relation': {}, 'ISSN': ['2059-3635'], 'subject': ['Cancer Research', 'Genetics'], 'container-title-short': 'Sig Transduct Target Ther', 'published': {'date-parts': [[2023, 9, 20]]}, 'assertion': [ { 'value': '20 January 2023', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '9 June 2023', 'order': 2, 'name': 'revised', 'label': 'Revised', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '31 July 2023', 'order': 3, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '20 September 2023', 'order': 4, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'The authors declare no competing interests. Figures were created with ' 'biorender.com.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}], 'article-number': '357'}
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