{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:28:19Z","timestamp":1792013299692,"version":"4.4.0"},"reference-count":59,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","award":["POR FESR 2014\/2020"],"award-info":[{"award-number":["POR FESR 2014\/2020"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Butyrate is a major gut microbiome metabolite that regulates several defense mechanisms against infectious diseases. Alterations in the gut microbiome, leading to reduced butyrate production, have been reported in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A new butyrate releaser, useful for all the known applications of butyrate, presenting physiochemical characteristics suitable for easy oral administration, (N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), has been recently developed. We investigated the protective action of FBA against SARS-CoV-2 infection in the human small intestine and enterocytes. Relevant aspects of SARS-CoV-2 infection were assessed: infectivity, host functional receptor angiotensin-converting enzyme-2 (ACE2), transmembrane protease serine 2 (TMPRSS2), neuropilin-1 (NRP1), pro-inflammatory cytokines expression, genes involved in the antiviral response and the activation of Nf-kB nuclear factor (erythroid-derived 2-like) 2 (Nfr2) pathways. We found that FBA positively modulates the crucial aspects of the infection in small intestinal biopsies and human enterocytes, reducing the expression of ACE2, TMPRSS2 and NRP1, pro-inflammatory cytokines interleukin (IL)-15, monocyte chemoattractant protein-1 (MCP-1) and TNF-\u03b1, and regulating several genes involved in antiviral pathways. FBA was also able to reduce the number of SARS-CoV-2-infected cells, and ACE2, TMPRSS2 and NRP1 expression. Lastly, through the inhibition of Nf-kB and the up-regulation of Nfr2, it was also able to reduce the expression of pro-inflammatory cytokines IL-15, MCP-1 and TNF-\u03b1 in human enterocytes. The new butyrate releaser, FBA, exerts a preventive action against SARS-CoV-2 infection. It could be considered as an innovative strategy to limit COVID-19.<\/jats:p>","DOI":"10.3390\/molecules27030862","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T22:00:56Z","timestamp":1643320856000},"page":"862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A New Butyrate Releaser Exerts a Protective Action against SARS-CoV-2 Infection in Human Intestine"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-1408","authenticated-orcid":false,"given":"Lorella","family":"Paparo","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Mediche Translazionali, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonia","family":"Maglio","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche Translazionali, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Cortese","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche Translazionali, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bruno","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche Translazionali, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-1259","authenticated-orcid":false,"given":"Mario","family":"Capasso","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Punzo","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche Translazionali, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9552-7192","authenticated-orcid":false,"given":"Vito Alessandro","family":"Lasorsa","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Viscardi","sequence":"additional","affiliation":[{"name":"DAI Medicina di Laboratorio e Trasfusionale, AOU Azienda Ospedaliera, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Fusco","sequence":"additional","affiliation":[{"name":"DAI Medicina di Laboratorio e Trasfusionale, AOU Azienda Ospedaliera, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pellegrino","family":"Cerino","sequence":"additional","affiliation":[{"name":"DAI Medicina di Laboratorio e Trasfusionale, AOU Azienda Ospedaliera, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Romano","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Troncone","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche Translazionali, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0970-7243","authenticated-orcid":false,"given":"Massimo","family":"Zollo","sequence":"additional","affiliation":[{"name":"CEINGE\u2014Advanced Biotechnologies s.c.ar.l., Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche (DMMBM), Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"},{"name":"DAI Medicina di Laboratorio e Trasfusionale, AOU Azienda Ospedaliera, Universit\u00e0 degli Studi di Napoli \u201cFederico II\u201d, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1111\/febs.15375","article-title":"A Guide to COVID-19: A global pandemic caused by the novel coronavirus SARS-CoV-2","volume":"287","author":"Atzrodt","year":"2020","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/S1473-3099(20)30232-2","article-title":"Viral dynamics in mild and severe cases of COVID-19","volume":"20","author":"Liu","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1053\/j.gastro.2020.03.065","article-title":"Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis","volume":"159","author":"Cheung","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"697390","DOI":"10.3389\/fped.2021.697390","article-title":"Age-Related Differences in the Expression of Most Relevant Mediators of SARS-CoV-2 Infection in Human Respiratory and Gastrointestinal Tract","volume":"9","author":"Comegna","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Ojha","year":"2020","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1126\/science.abd3072","article-title":"Neuropilin-1 is a host factor for SARS-CoV-2 infection","volume":"370","author":"Daly","year":"2020","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/s41591-020-0901-9","article-title":"Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19","volume":"26","author":"Liao","year":"2020","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108393","DOI":"10.1016\/j.clim.2020.108393","article-title":"The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China","volume":"214","author":"Zhang","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"583777","DOI":"10.3389\/fphar.2020.583777","article-title":"Calming the Storm: Natural Immunosuppressants as Adjuvants to Target the Cytokine Storm in COVID-19","volume":"11","author":"Peter","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"eabe5040","DOI":"10.1126\/scisignal.abe5040","article-title":"Long-chain polyphosphates impair SARS-CoV-2 infection and replication","volume":"14","author":"Ferrucci","year":"2021","journal-title":"Sci. Signal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1053\/j.gastro.2020.05.048","article-title":"Alterations in Gut Microbiota of Patients with COVID-19 during Time of Hospitalization","volume":"159","author":"Zuo","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1093\/cid\/ciaa709","article-title":"Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza","volume":"71","author":"Gu","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1136\/gutjnl-2020-323020","article-title":"Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19","volume":"70","author":"Yeoh","year":"2021","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between microbiota and immunity in health and disease","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/gutjnl-2015-309728","article-title":"The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia","volume":"65","author":"Schuijt","year":"2016","journal-title":"Gut"},{"key":"ref_19","first-page":"2978","article-title":"Impact of gut colonization with butyrate producing microbiota on respiratory viral infection following allo-HCT","volume":"131","author":"Haak","year":"2018","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Coppola, S., Avagliano, C., Calignano, A., and Canani, R.B. (2021). The Protective Role of Butyrate against Obesity and Obesity-Related Diseases. Molecules, 26.","DOI":"10.3390\/molecules26030682"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3748\/wjg.v17.i12.1519","article-title":"Potential beneficial effects of butyrate in intestinal and extraintestinal diseases","volume":"17","author":"Leone","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"111385","DOI":"10.1016\/j.biopha.2021.111385","article-title":"In vivo bioavailability and in vitro toxicological evaluation of the new butyric acid releaser N-(1-carbamoyl-2-phenyl-ethyl) butyramide","volume":"137","author":"Russo","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wei, J., Alfajaro, M.M., Hanna, R.E., DeWeirdt, P.C., Strine, M.S., Lu-Culligan, W.J., Zhang, S.-M., Graziano, V.R., Schmitz, C.O., and Chen, J.S. (2020). Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection. bioRxiv.","DOI":"10.1101\/2020.06.16.155101"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"638446","DOI":"10.3389\/fimmu.2021.638446","article-title":"Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19","volume":"12","author":"Stoy","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102836","DOI":"10.1016\/j.ebiom.2020.102836","article-title":"Targeting innate immunity by blocking CD14: Novel approach to control inflammation and organ dysfunction in COVID-19 illness","volume":"57","author":"Martin","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Conte, C. (2021). Possible Link between SARS-CoV-2 Infection and Parkinson\u2019s Disease: The Role of Toll-Like Receptor 4. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137135"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1136\/gut.43.6.856","article-title":"Role of NF-\u03baB in immune and inflammatory responses in the gut","volume":"43","author":"Neurath","year":"1998","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1093\/ndt\/gfaa093","article-title":"ADAM17 inhibition may exert a protective effect on COVID-19","volume":"35","author":"Palau","year":"2020","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.molimm.2015.10.021","article-title":"TRAF6-mediated degradation of DOK3 is required for production of IL-6 and TNF\u03b1 in TLR9 signaling","volume":"68","author":"Liu","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","volume":"181","author":"Liu","year":"2020","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cytogfr.2020.05.003","article-title":"The cytokine storm in COVID-19: An overview of the involvement of the chemokine\/chemokine-receptor system","volume":"53","author":"Coperchini","year":"2020","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Fung, T.S., Liao, Y., and Liu, D.X. (2016). Regulation of Stress Responses and Translational Control by Coronavirus. Viruses, 8.","DOI":"10.3390\/v8070184"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cellsig.2011.01.014","article-title":"Nuclear factor p65 interacts with Keap1 to repress the Nrf2-ARE pathway","volume":"23","author":"Yu","year":"2011","journal-title":"Cell. Signal."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Neufeldt, C.J., Cerikan, B., Cortese, M., Frankish, J., Lee, J.Y., Plociennikowska, A., Heigwer, F., Joecks, S., Burkart, S.S., and Zander, D.Y. (2020). SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-\u03baB. bioRxiv.","DOI":"10.1101\/2020.07.21.212639"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1053\/j.gastro.2020.04.008","article-title":"High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From California","volume":"159","author":"Cholankeril","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.immuni.2018.04.022","article-title":"Dietary fiber confers protection against flu by shaping Ly6c\u2013patrolling monocyte hema topoiesis and CD8+ T cell metabolism","volume":"48","author":"Trompette","year":"2018","journal-title":"Immunity"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lu, W., Fang, Z., Liu, X., Li, L., Zhang, P., Zhao, J., Zhang, H., and Chen, W. (2021). The Potential Role of Probiotics in Protection against Influenza a Virus Infection in Mice. Foods, 10.","DOI":"10.3390\/foods10040902"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Raso, G.M., Simeoli, R., Russo, R., Iacono, A., Santoro, A., Paciello, O., Ferrante, M.C., Canani, R.B., Calignano, A., and Meli, R. (2013). Effects of Sodium Butyrate and Its Synthetic Amide Derivative on Liver Inflammation and Glucose Tolerance in an Animal Model of Steatosis Induced by High Fat Diet. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068626"},{"key":"ref_39","first-page":"1484","article-title":"An orally administered butyrate-releasing derivative reduces neutrophil recruitment and inflammation in dextran sulphate sodium-induced murine colitis","volume":"174","author":"SSimeoli","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1161\/HYPERTENSIONAHA.120.16647","article-title":"Butyrate Regulates COVID-19\u2013Relevant Genes in Gut Epithelial Organoids from Normotensive Rats","volume":"77","author":"Li","year":"2021","journal-title":"Hypertension"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"841","DOI":"10.3920\/BM2016.0197","article-title":"Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells","volume":"8","author":"Elce","year":"2017","journal-title":"Benef. Microbes."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41401-020-0485-4","article-title":"Structural and functional properties of SARS-CoV-2 spike protein: Potential antivirus drug development for COVID-19","volume":"41","author":"Huang","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3389\/fmed.2020.00292","article-title":"The Use of Microbial Accessible and Fermentable Carbohydrates and\/or Butyrate as Supportive Treatment for Patients with Coronavirus SARS-CoV-2 Infection","volume":"7","author":"Archer","year":"2020","journal-title":"Front. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100831","DOI":"10.1016\/j.eclinm.2021.100831","article-title":"Reduced inflammatory responses to SARS-CoV-2 infection in children presenting to hospital with COVID-19 in China","volume":"34","author":"Qian","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"21697","DOI":"10.1038\/s41598-020-78710-7","article-title":"Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19","volume":"10","author":"Holter","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41577-020-0311-8","article-title":"The trinity of COVID-19: Immunity, inflammation and intervention","volume":"20","author":"Tay","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41591-020-1051-9","article-title":"An inflammatory cytokine signature predicts COVID-19 severity and survival","volume":"26","author":"Huang","year":"2020","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jaci.2020.10.007","article-title":"Factors associated with adverse COVID-19 outcomes in patients with psoriasis\u2014Insights from a global registry\u2013based study","volume":"147","author":"Mahil","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/S0140-6736(20)30858-8","article-title":"Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed","volume":"395","author":"Feldmann","year":"2020","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1053\/j.gastro.2020.05.032","article-title":"Corticosteroids, But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry","volume":"159","author":"Brenner","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"598444","DOI":"10.3389\/fimmu.2020.598444","article-title":"NF-\u03baB Pathway as a Potential Target for Treatment of Critical Stage COVID-19 Patients","volume":"11","author":"Kircheis","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1042\/BST20150014","article-title":"Dissecting molecular cross-talk between Nrf2 and NF-\u03baB response pathways","volume":"43","author":"Wardyn","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1042\/BST20150054","article-title":"Nrf2 as a master regulator of tissue damage control and disease tolerance to infection","volume":"43","author":"Soares","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15244","DOI":"10.1074\/jbc.M113.540633","article-title":"Transcription Factors NRF2 and NF-\u03baB Are Coordinated Effectors of the Rho Family, GTP-binding Protein RAC1 during Inflammation","volume":"289","author":"Cuadrado","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.1038\/s41467-020-18764-3","article-title":"SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate","volume":"11","author":"Olagnier","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"771555","DOI":"10.3389\/fphar.2021.771555","article-title":"Large Screening Identifies ACE2 Positively Correlates With NF-\u03baB Signaling Activity and Targeting NF-\u03baB Signaling Drugs Suppress ACE2 Levels","volume":"12","author":"Yan","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jinf.2020.07.016","article-title":"Differential immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung and intestinal cells: Implications for treatment with IFN-\u03b2 and IFN inducer","volume":"81","author":"Shuai","year":"2020","journal-title":"J. Infect."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1016\/S2666-5247(20)30004-5","article-title":"Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: An observational study","volume":"1","author":"Chu","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Vitale, S., Strisciuglio, C., Pisapia, L., Miele, E., Barba, P., Vitale, A., Cenni, S., Bassi, V., Maglio, M., and Del Pozzo, G. (2017). Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182313"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/3\/862\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:09:20Z","timestamp":1760134160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/3\/862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,27]]},"references-count":59,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["molecules27030862"],"URL":"https:\/\/doi.org\/10.3390\/molecules27030862","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,27]]}}}