{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:51:07Z","timestamp":1791471067719,"version":"4.3.4"},"reference-count":161,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI135128"],"award-info":[{"award-number":["R01AI135128"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R01 HL169974-01"],"award-info":[{"award-number":["R01 HL169974-01"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bull Math Biol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The mechanistic target of rapamycin complex 1 (mTORC1) has been implicated in coronavirus pathogenesis, yet its precise role in shaping antiviral defenses in pneumocytes remains unresolved. This study combines\n                    <jats:italic>ex vivo<\/jats:italic>\n                    human lung tissue assays with a literature-curated, logic-based (Boolean) signaling model to study how mTORC1 influences SARS-CoV-2 replication and type-I interferon (IFN) responses. Our in-vitro data showed that pharmacologic inhibition of mTORC1 with sirolimus was associated with reduced viral replication and increased IFN-\n                    <jats:inline-formula>\n                      <jats:alternatives>\n                        <jats:tex-math>$$\\beta $$<\/jats:tex-math>\n                        <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                          <mml:mi>\u03b2<\/mml:mi>\n                        <\/mml:math>\n                      <\/jats:alternatives>\n                    <\/jats:inline-formula>\n                    expression across donor samples. To interpret these data, we constructed a network integrating inflammation, stress, apoptosis, and RIG-I\u2013IFN signaling, and evaluated four mechanistic hypotheses for explaining our experiments in which mTORC1 either promotes replication, inhibits IFN, both, or neither. The model was constructed according to the best evidence in the literature and evaluated against 56 independent protein\/phosphoprotein readouts from 26 studies not used for model construction; the model achieved high qualitative accuracy overall (F1\n                    <jats:inline-formula>\n                      <jats:alternatives>\n                        <jats:tex-math>$$\\gtrsim 0.75$$<\/jats:tex-math>\n                        <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                          <mml:mrow>\n                            <mml:mo>\u2273<\/mml:mo>\n                            <mml:mn>0.75<\/mml:mn>\n                          <\/mml:mrow>\n                        <\/mml:math>\n                      <\/jats:alternatives>\n                    <\/jats:inline-formula>\n                    ) and on live-virus experiments (F1\n                    <jats:inline-formula>\n                      <jats:alternatives>\n                        <jats:tex-math>$$\\gtrsim 0.9$$<\/jats:tex-math>\n                        <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                          <mml:mrow>\n                            <mml:mo>\u2273<\/mml:mo>\n                            <mml:mn>0.9<\/mml:mn>\n                          <\/mml:mrow>\n                        <\/mml:math>\n                      <\/jats:alternatives>\n                    <\/jats:inline-formula>\n                    ). We found that the hypotheses where mTORC1 promotes viral replication, inhibits IFN, or both were able to qualitatively reproduce the empirical data,\n                    <jats:italic>i.e<\/jats:italic>\n                    ., mTORC1 inhibition by sirolimus leads to lower viral replication and higher IFN expression. We queried the robustness of those predictions through a systematic edge knock-in\/knockout screen generating 6,328 network variants per scenario (25,312 total). We found that the scenario where mTORC1 enhances viral replication is the more plausible, due to parsimony (this mechanism is also observed in other viral infections), higher robustness (more variants still reproduce the result), and stronger inhibition that is more likely to be observed in biological experiments with low statistical power. This scenario supports the idea that the mTORC1 effects on IFN expression are indirectly mediated by viral replication itself.\n                  <\/jats:p>","DOI":"10.1007\/s11538-026-01701-8","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:17:59Z","timestamp":1788355079000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["mTORC1 Promotes SARS-CoV-2 Replication and Attenuates Type I Interferon Responses in the Alveolar Epithelium: A Computational and Experimental Study"],"prefix":"10.1007","volume":"88","author":[{"given":"Achyudhan R.","family":"Kutuva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique AL","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe T.","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Schaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borna","family":"Mehrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Laubenbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"issue":"4","key":"1701_CR1","doi-asserted-by":"publisher","first-page":"00074","DOI":"10.1128\/msphere.00074-22","volume":"7","author":"B Adhikari","year":"2022","unstructured":"Adhikari B, Scindia Y, Sordo Vieira L, Assis Lopes Ribeiro H, Masison J, Yang N, Fonseca LL, Wheeler M, Knapp AC, Mei Y et al (2022) Computational modeling of macrophage iron sequestration during host defense against aspergillus. Msphere 7(4):00074\u201322","journal-title":"Msphere"},{"key":"1701_CR2","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1073\/pnas.0912344107","volume":"107","author":"T Alain","year":"2010","unstructured":"Alain T, Lun X, Martineau Y, Sean P, Pulendran B, Petroulakis E, Zemp FJ, Lemay CG, Roy D, Bell JC, Thomas G, Kozma SC, Forsyth PA, Costa-Mattioli M, Sonenberg N (2010) Vesicular stomatitis virus oncolysis is potentiated by impairing mtorc1-dependent type i ifn production. Proc Natl Acad Sci USA 107:1576\u201381","journal-title":"Proc Natl Acad Sci USA"},{"key":"1701_CR3","doi-asserted-by":"publisher","first-page":"9090","DOI":"10.3390\/ijms25169090","volume":"25","author":"B Alhasan","year":"2024","unstructured":"Alhasan B, Gladova YA, Sverchinsky DV, Aksenov ND, Margulis BA, Guzhova IV (2024) Hsp70 negatively regulates autophagy via governing ampk activation, and dual hsp70-autophagy inhibition induces synergetic cell death in nsclc cells. Int J Mol Sci 25:9090","journal-title":"Int J Mol Sci"},{"key":"1701_CR4","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s40246-020-00290-4","volume":"14","author":"C Anastassopoulou","year":"2020","unstructured":"Anastassopoulou C, Gkizarioti Z, Patrinos GP, Tsakris A (2020) Human genetic factors associated with susceptibility to sars-cov-2 infection and covid-19 disease severity. Hum Genomics 14:40","journal-title":"Hum Genomics"},{"key":"1701_CR5","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.1038\/s44319-024-00164-z","volume":"25","author":"P Antonellis","year":"2024","unstructured":"Antonellis P, Ferrucci V, Miceli M, Bibbo F, Asadzadeh F, Gorini F, Mattivi A, Boccia A, Russo R, Andolfo I, Lasorsa VA, Cantalupo S, Fusco G, Viscardi M, Brandi S, Cerino P, Monaco V, Choi D-R, Cheong J-H, Iolascon A, Amente S, Monti M, Fava LL, Capasso M, Kim H-Y, Zollo M (2024) Targeting atp2b1 impairs pi3k\/akt\/foxo signaling and reduces sars-cov-2 infection and replication. EMBO Rep 25:2974\u20133007","journal-title":"EMBO Rep"},{"key":"1701_CR6","doi-asserted-by":"crossref","unstructured":"Arjsri P, Srisawad K, Mapoung S, Semmarath W, Thippraphan P, Umsumarng S, Yodkeeree S, Dejkriengkraikul P (2022) Hesperetin from root extract of $$<$$i$$>$$clerodendrum petasites$$<$$\/i$$>$$ s. moore inhibits sars-cov-2 spike protein s1 subunit-induced nlrp3 inflammasome in a549 lung cells via modulation of the akt\/mapk\/ap-1 pathway. Int J Mol Sci 23:10346","DOI":"10.3390\/ijms231810346"},{"key":"1701_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116671","volume":"233","author":"S Arora","year":"2019","unstructured":"Arora S, Ahmad S, Irshad R, Goyal Y, Rafat S, Siddiqui N, Dev K, Husain M, Ali S, Mohan A, Syed MA (2019) Tlrs in pulmonary diseases. Life Sci 233:116671","journal-title":"Life Sci"},{"key":"1701_CR8","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1161\/ATVBAHA.115.306931","volume":"36","author":"VR Babaev","year":"2016","unstructured":"Babaev VR, Ding L, Zhang Y, May JM, Lin PC, Fazio S, Linton MF (2016) Macrophage ikk$$\\alpha $$ deficiency suppresses akt phosphorylation, reduces cell survival, and decreases early atherosclerosis. Arterioscler Thromb Vasc Biol 36:598\u2013607","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"1701_CR9","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/sj.onc.1204124","volume":"20","author":"T Bartke","year":"2001","unstructured":"Bartke T, Siegmund D, Peters N, Reichwein M, Henkler F, Scheurich P, Wajant H (2001) p53 upregulates cflip, inhibits transcription of nf-kappab-regulated genes and induces caspase-8-independent cell death in dld-1 cells. Oncogene 20:571\u201380","journal-title":"Oncogene"},{"key":"1701_CR10","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/j.drudis.2021.11.002","volume":"27","author":"MS Basile","year":"2022","unstructured":"Basile MS, Cavalli E, McCubrey J, Hern\u00e1ndez-Bello J, Mu\u00f1oz-Valle JF, Fagone P, Nicoletti F (2022) The pi3k\/akt\/mtor pathway: A potential pharmacological target in covid-19. Drug Discovery Today 27:848\u2013856","journal-title":"Drug Discovery Today"},{"key":"1701_CR11","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s00428-021-03053-1","volume":"478","author":"H B\u00f6sm\u00fcller","year":"2021","unstructured":"B\u00f6sm\u00fcller H, Matter M, Fend F, Tzankov A (2021) The pulmonary pathology of covid-19. Virchows Archiv an international journal of pathology 478:137\u2013150","journal-title":"Virchows Archiv an international journal of pathology"},{"key":"1701_CR12","doi-asserted-by":"crossref","unstructured":"Bramante CT, Beckman KB, Mehta T, Karger AB, Odde DJ, Tignanelli CJ, Buse JB, Johnson DM, Watson RHB, Daniel JJ, Liebovitz DM, Nicklas JM, Cohen K, Puskarich MA, Belani HK, Siegel LK, Klatt NR, Anderson B, Hartman KM, Rao V, Hagen AA, Patel B, Fenno SL, Avula N, Reddy NV, Erickson SM, Fricton RD, Lee S, Griffiths G, Pullen MF, Thompson JL, Sherwood NE, Murray TA, Rose MR, Boulware DR, Huling JD, Team C-OS (2024) Favorable antiviral effect of metformin on sars-cov-2 viral load in a randomized, placebo-controlled clinical trial of covid-19. Clinical infectious diseases an official publication of the Infectious Diseases Society of America 79:354\u2013363","DOI":"10.1101\/2023.06.06.23290989"},{"key":"1701_CR13","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12918-015-0163-1","volume":"9","author":"M Brandon","year":"2015","unstructured":"Brandon M, Howard B, Lawrence C, Laubenbacher R (2015) Iron acquisition and oxidative stress response in aspergillus fumigatus. BMC Syst Biol 9:19","journal-title":"BMC Syst Biol"},{"key":"1701_CR14","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1093\/cvr\/cvq076","volume":"86","author":"AR Brasier","year":"2010","unstructured":"Brasier AR (2010) The nuclear factor-kappab-interleukin-6 signalling pathway mediating vascular inflammation. Cardiovasc Res 86:211\u20138","journal-title":"Cardiovasc Res"},{"key":"1701_CR15","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1101\/gad.1256804","volume":"18","author":"J Brugarolas","year":"2004","unstructured":"Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG (2004) Regulation of mtor function in response to hypoxia by redd1 and the tsc1\/tsc2 tumor suppressor complex. Genes & development 18:2893\u2013904","journal-title":"Genes & development"},{"key":"1701_CR16","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.cell.2008.06.028","volume":"134","author":"AV Budanov","year":"2008","unstructured":"Budanov AV, Karin M (2008) p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mtor signaling. Cell 134:451\u201360","journal-title":"Cell"},{"key":"1701_CR17","doi-asserted-by":"crossref","unstructured":"Campbell J, Ciesielski CJ, Hunt AE, Horwood NJ, Beech JT, Hayes LA, Denys A, Feldmann M, Brennan FM, Foxwell BMJ (2004) A novel mechanism for tnf-alpha regulation by p38 mapk: involvement of nf-kappa b with implications for therapy in rheumatoid arthritis. J Invest Med (Baltimore Md 1950) 173:6928\u201337","DOI":"10.4049\/jimmunol.173.11.6928"},{"key":"1701_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.110412","volume":"146","author":"M Carcaterra","year":"2021","unstructured":"Carcaterra M, Caruso C (2021) Alveolar epithelial cell type ii as main target of sars-cov-2 virus and covid-19 development via nf-kb pathway deregulation: A physio-pathological theory. Med Hypotheses 146:110412","journal-title":"Med Hypotheses"},{"key":"1701_CR19","doi-asserted-by":"publisher","first-page":"5527","DOI":"10.1038\/onc.2008.247","volume":"27","author":"A Carracedo","year":"2008","unstructured":"Carracedo A, Pandolfi PP (2008) The pten-pi3k pathway: of feedbacks and cross-talks. Oncogene 27:5527\u201341","journal-title":"Oncogene"},{"key":"1701_CR20","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1165\/rcmb.2008-0419OC","volume":"42","author":"S-I Cha","year":"2010","unstructured":"Cha S-I, Groshong SD, Frankel SK, Edelman BL, Cosgrove GP, Terry-Powers JL, Remigio LK, Curran-Everett D, Brown KK, Cool CD, Riches DWH (2010) Compartmentalized expression of c-flip in lung tissues of patients with idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol 42:140\u20138","journal-title":"Am J Respir Cell Mol Biol"},{"key":"1701_CR21","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/S1074-7613(00)80400-8","volume":"7","author":"PM Chaudhary","year":"1997","unstructured":"Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L (1997) Death receptor 5, a new member of the tnfr family, and dr4 induce fadd-dependent apoptosis and activate the nf-kappab pathway. Immunity 7:821\u201330","journal-title":"Immunity"},{"key":"1701_CR22","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.210069","volume":"11","author":"PS Cheema","year":"2021","unstructured":"Cheema PS, Nandi D, Nag A (2021) Exploring the therapeutic potential of forkhead box o for outfoxing covid-19. Open Biol 11:210069","journal-title":"Open Biol"},{"key":"1701_CR23","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.molcel.2009.04.029","volume":"34","author":"W Chen","year":"2009","unstructured":"Chen W, Sun Z, Wang X-J, Jiang T, Huang Z, Fang D, Zhang DD (2009) Direct interaction between nrf2 and p21(cip1\/waf1) upregulates the nrf2-mediated antioxidant response. Mol Cell 34:663\u201373","journal-title":"Mol Cell"},{"key":"1701_CR24","first-page":"0129663","volume":"10","author":"B Chen","year":"2015","unstructured":"Chen B, Xu X, Luo J, Wang H, Zhou S (2015) Rapamycin enhances the anti-cancer effect of dasatinib by suppressing src\/pi3k\/mtor pathway in nsclc cells. PLoS ONE 10:0129663","journal-title":"PLoS ONE"},{"key":"1701_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2021.102000","volume":"65","author":"M Chen","year":"2020","unstructured":"Chen M, Chen Z, Huang D, Sun C, Xie J, Chen T, Zhao X, Huang Y, Li D, Wu B, Wu D (2020) Myricetin inhibits tnf-$$\\alpha $$-induced inflammation in a549 cells via the sirt1\/nf-$$\\kappa $$b pathway. Pulmonary pharmacology & therapeutics 65:102000","journal-title":"Pulmonary pharmacology & therapeutics"},{"issue":"2","key":"1701_CR26","doi-asserted-by":"publisher","first-page":"2618","DOI":"10.3934\/math.2022147","volume":"7","author":"S Chowdhury","year":"2022","unstructured":"Chowdhury S, Chowdhury J, Ahmed SF, Agarwal P, Badruddin IA, Kamangar S et al (2022) Mathematical modelling of covid-19 disease dynamics: Interaction between immune system and sars-cov-2 within host. AIMS Mathematics 7(2):2618\u20132633","journal-title":"AIMS Mathematics"},{"issue":"Pt 1","key":"1701_CR27","first-page":"1","volume":"326","author":"GM Cohen","year":"1997","unstructured":"Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326(Pt 1):1\u201316","journal-title":"Biochem J"},{"key":"1701_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2008.04.041","volume":"320","author":"L Covarrubias","year":"2008","unstructured":"Covarrubias L, Hern\u00e1ndez-Garc\u00eda D, Schnabel D, Salas-Vidal E, Castro-Obreg\u00f3n S (2008) Function of reactive oxygen species during animal development: passive or active? Dev Biol 320:1\u201311","journal-title":"Dev Biol"},{"key":"1701_CR29","doi-asserted-by":"crossref","unstructured":"COVID-19 Disease Map Community, Ostaszewski M, Niarakis A, Mazein A, Kuperstein I, Phair R, Orta-Resendiz A, Singh V, Aghamiri SS, Acencio ML, Glaab E, Ruepp A, Fobo G, Montrone C, Brauner B, Frishman G, G\u00f3mez LCM, Somers J, Hoch M, Gupta SK, Scheel J, Borlinghaus H, Czauderna T, Schreiber F, Montagud A, Leon MP, Funahashi A, Hiki Y, Hiroi N, Yamada TG, Dr\u00e4ger A, Renz A, Naveez M, Bocskei Z, Messina F, B\u00f6rnigen D, Fergusson L, Conti M, Rameil M, Nakonecnij V, Vanhoefer J, Schmiester L, Wang M, Ackerman EE, Shoemaker JE, Zucker J, Oxford K, Teuton J, Kocakaya E, Waard A, (2021) Covid19 disease map, a computational knowledge repository of virus-host interaction mechanisms. Mol Syst Biol 17(10):10387","DOI":"10.15252\/msb.202110387"},{"key":"1701_CR30","unstructured":"COVID-19 Disease Map. an online knowledge repository of molecular mechanisms of COVID-19, community-driven effort to assemble virus\u2013host interaction diagrams based on literature evidence (2026) https:\/\/covid.pages.uni.lu\/"},{"key":"1701_CR31","doi-asserted-by":"publisher","first-page":"21064","DOI":"10.18632\/oncotarget.8383","volume":"7","author":"HC Dan","year":"2016","unstructured":"Dan HC, Antonia RJ, Baldwin AS (2016) Pi3k\/akt promotes feedforward mtorc2 activation through ikk$$\\alpha $$. Oncotarget 7:21064\u201375","journal-title":"Oncotarget"},{"key":"1701_CR32","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1038\/cddis.2015.403","volume":"7","author":"TP Das","year":"2016","unstructured":"Das TP, Suman S, Alatassi H, Ankem MK, Damodaran C (2016) Inhibition of akt promotes foxo3a-dependent apoptosis in prostate cancer. Cell death & disease 7:2111","journal-title":"Cell death & disease"},{"key":"1701_CR33","doi-asserted-by":"publisher","first-page":"32377","DOI":"10.1074\/jbc.273.49.32377","volume":"273","author":"K Du","year":"1998","unstructured":"Du K, Montminy M (1998) Creb is a regulatory target for the protein kinase akt\/pkb. J Biol Chem 273:32377\u20139","journal-title":"J Biol Chem"},{"key":"1701_CR34","doi-asserted-by":"publisher","unstructured":"Eltzschig H, Yuan X, Kim J, Wang Y, Mangala L, Rodriguez-Aguayo C, Lopez-Berestein G, Sood A, Ruan W, Weng T, et\u00a0al (2023) Hif-dependent induction of alveolar mir-147 dampens sars-cov-2 immune evasion https:\/\/doi.org\/10.21203\/rs.3.rs-2319034\/v1","DOI":"10.21203\/rs.3.rs-2319034\/v1"},{"key":"1701_CR35","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1038\/sj.onc.1208421","volume":"24","author":"A Essafi","year":"2005","unstructured":"Essafi A, Mattos S, Hassen YAM, Soeiro I, Mufti GJ, Thomas NSB, Medema RH, Lam EW-F (2005) Direct transcriptional regulation of bim by foxo3a mediates sti571-induced apoptosis in bcr-abl-expressing cells. Oncogene 24:2317\u201329","journal-title":"Oncogene"},{"key":"1701_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102571","volume":"19","author":"P Fagone","year":"2020","unstructured":"Fagone P, Ciurleo R, Lombardo SD, Iacobello C, Palermo CI, Shoenfeld Y, Bendtzen K, Bramanti P, Nicoletti F (2020) Transcriptional landscape of sars-cov-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies. Autoimmun Rev 19:102571","journal-title":"Autoimmun Rev"},{"issue":"6","key":"1701_CR37","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11538-025-01442-0","volume":"87","author":"L Fan","year":"2025","unstructured":"Fan L, Qiu Z, Deng Q, Guo T, Rong L (2025) Modeling sars-cov-2 infection dynamics: Insights into viral clearance and immune synergy. Bull Math Biol 87(6):67","journal-title":"Bull Math Biol"},{"key":"1701_CR38","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s12026-022-09268-x","volume":"70","author":"S Fattahi","year":"2022","unstructured":"Fattahi S, Khalifehzadeh-Esfahani Z, Mohammad-Rezaei M, Mafi S, Jafarinia M (2022) Pi3k\/akt\/mtor pathway: a potential target for anti-sars-cov-2 therapy. Immunol Res 70:269\u2013275","journal-title":"Immunol Res"},{"key":"1701_CR39","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.tcb.2010.03.004","volume":"20","author":"Z Feng","year":"2010","unstructured":"Feng Z, Levine AJ (2010) The regulation of energy metabolism and the igf-1\/mtor pathways by the p53 protein. Trends Cell Biol 20:427\u201334","journal-title":"Trends Cell Biol"},{"key":"1701_CR40","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/cdd.2011.179","volume":"19","author":"EC Ferber","year":"2012","unstructured":"Ferber EC, Peck B, Delpuech O, Bell GP, East P, Schulze A (2012) Foxo3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression. Cell Death Differ 19:968\u201379","journal-title":"Cell Death Differ"},{"key":"1701_CR41","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.3390\/microorganisms10101996","volume":"10","author":"CB Forsyth","year":"2022","unstructured":"Forsyth CB, Zhang L, Bhushan A, Swanson B, Zhang L, Mamede JI, Voigt RM, Shaikh M, Engen PA, Keshavarzian A (2022) The sars-cov-2 s1 spike protein promotes mapk and nf-kb activation in human lung cells and inflammatory cytokine production in human lung and intestinal epithelial cells. Microorganisms 10:1996","journal-title":"Microorganisms"},{"key":"1701_CR42","doi-asserted-by":"publisher","first-page":"473","DOI":"10.3390\/ijms21020473","volume":"21","author":"CM Garc\u00eda-Cuellar","year":"2020","unstructured":"Garc\u00eda-Cuellar CM, Chirino YI, Morales-B\u00e1rcenas R, Soto-Reyes E, Quintana-Belmares R, Santib\u00e1\u00f1ez-Andrade M, S\u00e1nchez-P\u00e9rez Y (2020) Airborne particulate matter ($${\\rm pm}_{10}$$) inhibits apoptosis through pi3k\/akt\/foxo3a pathway in lung epithelial cells: The role of a second oxidant stimulus. Int J Mol Sci 21:473","journal-title":"Int J Mol Sci"},{"key":"1701_CR43","doi-asserted-by":"publisher","first-page":"18180","DOI":"10.1038\/s41598-019-54567-3","volume":"9","author":"J Gimenes-Junior","year":"2019","unstructured":"Gimenes-Junior J, Owuar N, Vari HR, Li W, Xander N, Kotnala S, Sajjan US (2019) Foxo3a regulates rhinovirus-induced innate immune responses in airway epithelial cells. Sci Rep 9:18180","journal-title":"Sci Rep"},{"key":"1701_CR44","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.yjmcc.2020.05.007","volume":"144","author":"JM Grimes","year":"2020","unstructured":"Grimes JM, Grimes KV (2020) p38 mapk inhibition: A promising therapeutic approach for covid-19. J Mol Cell Cardiol 144:63\u201365","journal-title":"J Mol Cell Cardiol"},{"key":"1701_CR45","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","volume":"9","author":"Q Guo","year":"2024","unstructured":"Guo Q, Jin Y, Chen X, Ye X, Shen X, Lin M, Zeng C, Zhou T, Zhang J (2024) Nf-$$\\kappa $$b in biology and targeted therapy: new insights and translational implications. Signal Transduct Target Ther 9:53","journal-title":"Signal Transduct Target Ther"},{"key":"1701_CR46","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nrm3311","volume":"13","author":"DG Hardie","year":"2012","unstructured":"Hardie DG, Ross FA, Hawley SA (2012) Ampk: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13:251\u201362","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1701_CR47","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10787-020-00773-9","volume":"29","author":"A Hariharan","year":"2021","unstructured":"Hariharan A, Hakeem AR, Radhakrishnan S, Reddy MS, Rela M (2021) The role and therapeutic potential of nf-kappa-b pathway in severe covid-19 patients. Inflammopharmacology 29:91\u2013100","journal-title":"Inflammopharmacology"},{"key":"1701_CR48","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1042\/BJ20131344","volume":"459","author":"SA Hawley","year":"2014","unstructured":"Hawley SA, Ross FA, Gowans GJ, Tibarewal P, Leslie NR, Hardie DG (2014) Phosphorylation by akt within the st loop of ampk-$$\\alpha $$1 down-regulates its activation in tumour cells. Biochem J 459:275\u201387","journal-title":"Biochem J"},{"key":"1701_CR49","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1128\/MCB.00670-13","volume":"34","author":"G He","year":"2014","unstructured":"He G, Zhang Y-W, Lee J-H, Zeng SX, Wang YV, Luo Z, Dong XC, Viollet B, Wahl GM, Lu H (2014) Amp-activated protein kinase induces p53 by phosphorylating mdmx and inhibiting its activity. Mol Cell Biol 34:148\u201357","journal-title":"Mol Cell Biol"},{"key":"1701_CR50","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S0092-8674(04)00302-2","volume":"117","author":"MC-T Hu","year":"2004","unstructured":"Hu MC-T, Lee D-F, Xia W, Golfman LS, Ou-Yang F, Yang J-Y, Zou Y, Bao S, Hanada N, Saso H, Kobayashi R, Hung M-C (2004) Ikappab kinase promotes tumorigenesis through inhibition of forkhead foxo3a. Cell 117:225\u201337","journal-title":"Cell"},{"key":"1701_CR51","doi-asserted-by":"publisher","first-page":"7455","DOI":"10.1073\/pnas.1001006107","volume":"107","author":"W Hu","year":"2010","unstructured":"Hu W, Zhang C, Wu R, Sun Y, Levine A, Feng Z (2010) Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci USA 107:7455\u201360","journal-title":"Proc Natl Acad Sci USA"},{"key":"1701_CR52","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1423-0127-20-3","volume":"20","author":"W-C Huang","year":"2013","unstructured":"Huang W-C, Hung M-C (2013) Beyond nf-$$\\kappa $$b activation: nuclear functions of i$$\\kappa $$b kinase $$\\alpha $$. J Biomed Sci 20:3","journal-title":"J Biomed Sci"},{"key":"1701_CR53","doi-asserted-by":"crossref","unstructured":"Hwang J-W, Rajendrasozhan S, Yao H, Chung S, Sundar IK, Huyck HL, Pryhuber GS, Kinnula VL, Rahman I (2011) Foxo3 deficiency leads to increased susceptibility to cigarette smoke-induced inflammation, airspace enlargement, and chronic obstructive pulmonary disease. J Immunol (Baltimore Md 1950) 187:987\u201398","DOI":"10.4049\/jimmunol.1001861"},{"key":"1701_CR54","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","volume":"23","author":"CB Jackson","year":"2022","unstructured":"Jackson CB, Farzan M, Chen B, Choe H (2022) Mechanisms of sars-cov-2 entry into cells. Nat Rev Mol Cell Biol 23:3\u201320","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1701_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.104836","volume":"154","author":"A Jafarzadeh","year":"2021","unstructured":"Jafarzadeh A, Nemati M, Jafarzadeh S (2021) Contribution of stat3 to the pathogenesis of covid-19. Microb Pathog 154:104836","journal-title":"Microb Pathog"},{"key":"1701_CR56","doi-asserted-by":"publisher","first-page":"0077421","DOI":"10.1128\/Spectrum.00774-21","volume":"9","author":"M Jiang","year":"2021","unstructured":"Jiang M, Kolehmainen P, Kakkola L, Maljanen S, Mel\u00e9n K, Smura T, Julkunen I, \u00d6sterlund P (2021) Sars-cov-2 isolates show impaired replication in human immune cells but differential ability to replicate and induce innate immunity in lung epithelial cells. Microbiology spectrum 9:0077421","journal-title":"Microbiology spectrum"},{"key":"1701_CR57","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.bbrc.2023.08.063","volume":"679","author":"S Jiang","year":"2023","unstructured":"Jiang S, Yang H, Sun Z, Zhang Y, Li Y, Li J (2023) The basis of complications in the context of sars-cov-2 infection: Pathological activation of adam17. Biochem Biophys Res Commun 679:37\u201346","journal-title":"Biochem Biophys Res Commun"},{"key":"1701_CR58","first-page":"517","volume":"25","author":"IL Jung","year":"2010","unstructured":"Jung IL, Kang HJ, Kim KC, Kim IG (2010) Pten\/pakt\/p53 signaling pathway correlates with the radioresponse of non-small cell lung cancer. Int J Mol Med 25:517\u201323","journal-title":"Int J Mol Med"},{"key":"1701_CR59","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1023\/A:1009607607603","volume":"4","author":"H Jyonouchi","year":"1999","unstructured":"Jyonouchi H (1999) Airway epithelium and apoptosis. Apoptosis an international journal on programmed cell death 4:407\u201317","journal-title":"Apoptosis an international journal on programmed cell death"},{"key":"1701_CR60","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1089\/ars.2013.5746","volume":"21","author":"VO Kaminskyy","year":"2014","unstructured":"Kaminskyy VO, Zhivotovsky B (2014) Free radicals in cross talk between autophagy and apoptosis. Antioxidants & redox signaling 21:86\u2013102","journal-title":"Antioxidants & redox signaling"},{"key":"1701_CR61","unstructured":"Kanehisa Laboratories: KEGG: Kyoto Encyclopedia of Genes and Genomes. https:\/\/www.kegg.jp\/. Accessed: 2025-09-04"},{"key":"1701_CR62","doi-asserted-by":"publisher","first-page":"3249","DOI":"10.1126\/scisignal.aav3249","volume":"12","author":"D Kazyken","year":"2019","unstructured":"Kazyken D, Magnuson B, Bodur C, Acosta-Jaquez HA, Zhang D, Tong X, Barnes TM, Steinl GK, Patterson NE, Altheim CH, Sharma N, Inoki K, Cartee GD, Bridges D, Yin L, Riddle SM, Fingar DC (2019) Ampk directly activates mtorc2 to promote cell survival during acute energetic stress. Science signaling 12:3249","journal-title":"Science signaling"},{"key":"1701_CR63","doi-asserted-by":"publisher","first-page":"68563","DOI":"10.7554\/eLife.68563","volume":"10","author":"S Khan","year":"2021","unstructured":"Khan S, Shafiei MS, Longoria C, Schoggins JW, Savani RC, Zaki H (2021) Sars-cov-2 spike protein induces inflammation via tlr2-dependent activation of the nf-$$\\kappa $$b pathway. Elife 10:68563","journal-title":"Elife"},{"key":"1701_CR64","doi-asserted-by":"publisher","first-page":"42473","DOI":"10.1038\/srep42473","volume":"7","author":"C Klemm","year":"2017","unstructured":"Klemm C, Bruchhagen C, Kr\u00fcchten A, Niemann S, L\u00f6ffler B, Peters G, Ludwig S, Ehrhardt C (2017) Mitogen-activated protein kinases (mapks) regulate il-6 over-production during concomitant influenza virus and staphylococcus aureus infection. Sci Rep 7:42473","journal-title":"Sci Rep"},{"key":"1701_CR65","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1128\/MCB.21.4.1297-1310.2001","volume":"21","author":"C Koumenis","year":"2001","unstructured":"Koumenis C, Alarcon R, Hammond E, Sutphin P, Hoffman W, Murphy M, Derr J, Taya Y, Lowe SW, Kastan M, Giaccia A (2001) Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol 21:1297\u2013310","journal-title":"Mol Cell Biol"},{"key":"1701_CR66","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3389\/fonc.2018.00160","volume":"8","author":"N Koundouros","year":"2018","unstructured":"Koundouros N, Poulogiannis G (2018) Phosphoinositide 3-kinase\/akt signaling and redox metabolism in cancer. Front Oncol 8:160","journal-title":"Front Oncol"},{"key":"1701_CR67","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.mad.2014.06.002","volume":"139","author":"M Krze\u015bniak","year":"2014","unstructured":"Krze\u015bniak M, Zajkowicz A, Matuszczyk I, Rusin M (2014) Rapamycin prevents strong phosphorylation of p53 on serine 46 and attenuates activation of the p53 pathway in a549 lung cancer cells exposed to actinomycin d. Mech Ageing Dev 139:11\u201321","journal-title":"Mech Ageing Dev"},{"key":"1701_CR68","doi-asserted-by":"publisher","first-page":"8961","DOI":"10.1038\/sj.onc.1207230","volume":"22","author":"J Kucharczak","year":"2003","unstructured":"Kucharczak J, Simmons MJ, Fan Y, G\u00e9linas C (2003) To be, or not to be: Nf-kappab is the answer-role of rel\/nf-kappab in the regulation of apoptosis. Oncogene 22:8961\u201382","journal-title":"Oncogene"},{"key":"1701_CR69","first-page":"32","volume":"1870","author":"CF Labuschagne","year":"2018","unstructured":"Labuschagne CF, Zani F, Vousden KH (2018) Control of metabolism by p53 - cancer and beyond. Biochim Biophys Acta 1870:32\u201342","journal-title":"Biochim Biophys Acta"},{"key":"1701_CR70","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1189\/jlb.1208763","volume":"85","author":"MHW Laird","year":"2009","unstructured":"Laird MHW, Rhee SH, Perkins DJ, Medvedev AE, Piao W, Fenton MJ, Vogel SN (2009) Tlr4\/myd88\/pi3k interactions regulate tlr4 signaling. J Leukoc Biol 85:966\u201377","journal-title":"J Leukoc Biol"},{"key":"1701_CR71","first-page":"476","volume":"100","author":"JA Lednicky","year":"2020","unstructured":"Lednicky JA, Lauzard M, Fan ZH, Jutla A, Tilly TB, Gangwar M, Usmani M, Shankar SN, Mohamed K, Eiguren-Fernandez A, Stephenson CJ, Alam MM, Elbadry MA, Loeb JC, Subramaniam K, Waltzek TB, Cherabuddi K, Morris JG, Wu C-Y (2020) Viable sars-cov-2 in the air of a hospital room with covid-19 patients. International journal of infectious diseases IJID official publication of the International Society for Infectious Diseases 100:476\u2013482","journal-title":"International journal of infectious diseases IJID official publication of the International Society for Infectious Diseases"},{"key":"1701_CR72","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1161\/ATVBAHA.107.153304","volume":"28","author":"H-Y Lee","year":"2008","unstructured":"Lee H-Y, Youn S-W, Kim J-Y, Park K-W, Hwang C-I, Park W-Y, Oh B-H, Park Y-B, Walsh K, Seo J-S, Kim H-S (2008) Foxo3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-jun n-terminal kinase and nf-kappab. Arterioscler Thromb Vasc Biol 28:112\u201320","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"1701_CR73","doi-asserted-by":"publisher","first-page":"1158133","DOI":"10.3389\/fmolb.2023.1158133","volume":"10","author":"VS Lekshmi","year":"2023","unstructured":"Lekshmi VS, Asha K, Sanicas M, Asi A, Arya UM, Kumar B (2023) Pi3k\/akt\/nrf2 mediated cellular signaling and virus-host interactions: latest updates on the potential therapeutic management of sars-cov-2 infection. Front Mol Biosci 10:1158133","journal-title":"Front Mol Biosci"},{"key":"1701_CR74","doi-asserted-by":"publisher","first-page":"25754","DOI":"10.1038\/srep25754","volume":"6","author":"S-W Li","year":"2016","unstructured":"Li S-W, Wang C-Y, Jou Y-J, Yang T-C, Huang S-H, Wan L, Lin Y-J, Lin C-W (2016) Sars coronavirus papain-like protease induces egr-1-dependent up-regulation of tgf-$$\\beta $$1 via ros\/p38 mapk\/stat3 pathway. Sci Rep 6:25754","journal-title":"Sci Rep"},{"key":"1701_CR75","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s41392-020-00334-0","volume":"5","author":"S Li","year":"2020","unstructured":"Li S, Zhang Y, Guan Z, Li H, Ye M, Chen X, Shen J, Zhou Y, Shi Z-L, Zhou P, Peng K (2020) Sars-cov-2 triggers inflammatory responses and cell death through caspase-8 activation. Signal Transduct Target Ther 5:235","journal-title":"Signal Transduct Target Ther"},{"key":"1701_CR76","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.canlet.2020.03.007","volume":"478","author":"Y Li","year":"2020","unstructured":"Li Y, Liang R, Sun M, Li Z, Sheng H, Wang J, Xu P, Liu S, Yang W, Lu B, Zhang S, Shan C (2020) Ampk-dependent phosphorylation of hdac8 triggers pgm1 expression to promote lung cancer cell survival under glucose starvation. Cancer Lett 478:82\u201392","journal-title":"Cancer Lett"},{"key":"1701_CR77","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13578-015-0063-5","volume":"5","author":"C-H Lin","year":"2015","unstructured":"Lin C-H, Hong Y-C, Kao S-H (2015) Aeroallergen der p 2 induces apoptosis of bronchial epithelial beas-2b cells via activation of both intrinsic and extrinsic pathway. Cell & bioscience 5:71","journal-title":"Cell & bioscience"},{"key":"1701_CR78","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s42255-019-0157-1","volume":"2","author":"NXY Ling","year":"2020","unstructured":"Ling NXY, Kaczmarek A, Hoque A, Davie E, Ngoei KRW, Morrison KR, Smiles WJ, Forte GM, Wang T, Lie S, Dite TA, Langendorf CG, Scott JW, Oakhill JS, Petersen J (2020) mtorc1 directly inhibits ampk to promote cell proliferation under nutrient stress. Nat Metab 2:41\u201349","journal-title":"Nat Metab"},{"key":"1701_CR79","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/1476-4598-10-95","volume":"10","author":"J Liu","year":"2011","unstructured":"Liu J, Uematsu H, Tsuchida N, Ikeda M-A (2011) Essential role of caspase-8 in p53\/p73-dependent apoptosis induced by etoposide in head and neck carcinoma cells. Mol Cancer 10:95","journal-title":"Mol Cancer"},{"key":"1701_CR80","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1099\/jgv.0.000802","volume":"98","author":"Q Liu","year":"2017","unstructured":"Liu Q, Miller LC, Blecha F, Sang Y (2017) Reduction of infection by inhibiting mtor pathway is associated with reversed repression of type i interferon by porcine reproductive and respiratory syndrome virus. J Gen Virol 98:1316\u20131328","journal-title":"J Gen Virol"},{"key":"1701_CR81","doi-asserted-by":"crossref","unstructured":"Li L, Wu W, Huang W, Hu G, Yuan W, Li W (2013) Nf-$$\\kappa $$b rnai decreases the bax\/bcl-2 ratio and inhibits tnf-$$\\alpha $$-induced apoptosis in human alveolar epithelial cells. Inflammation research official journal of the European Histamine Research Society ... [et\u00a0al.] 62:387\u201397","DOI":"10.1007\/s00011-013-0590-7"},{"key":"1701_CR82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytox.2020.100029","volume":"2","author":"G Magro","year":"2020","unstructured":"Magro G (2020) Sars-cov-2 and covid-19: Is interleukin-6 (il-6) the culprit lesion of ards onset? what is there besides tocilizumab? sgp130fc. Cytokine X 2:100029","journal-title":"Cytokine X"},{"key":"1701_CR83","doi-asserted-by":"publisher","first-page":"5192","DOI":"10.1073\/pnas.1603435113","volume":"113","author":"Y Ma-Lauer","year":"2016","unstructured":"Ma-Lauer Y, Carbajo-Lozoya J, Hein MY, M\u00fcller MA, Deng W, Lei J, Meyer B, Kusov Y, Brunn B, Bairad DR, H\u00fcnten S, Drosten C, Hermeking H, Leonhardt H, Mann M, Hilgenfeld R, Brunn A (2016) p53 down-regulates sars coronavirus replication and is targeted by the sars-unique domain and plpro via e3 ubiquitin ligase rchy1. Proc Natl Acad Sci USA 113:5192\u2013201","journal-title":"Proc Natl Acad Sci USA"},{"key":"1701_CR84","doi-asserted-by":"publisher","first-page":"3664","DOI":"10.3390\/cancers12123664","volume":"12","author":"M Marku","year":"2020","unstructured":"Marku M, Verstraete N, Raynal F, Madrid-Menc\u00eda M, Domagala M, Fourni\u00e9 J-J, Ysebaert L, Poupot M, Pancaldi V (2020) Insights on tam formation from a boolean model of macrophage polarization based on in vitro studies. Cancers 12:3664","journal-title":"Cancers"},{"key":"1701_CR85","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1016\/j.molcel.2021.04.008","volume":"81","author":"L Martin-Sancho","year":"2021","unstructured":"Martin-Sancho L, Lewinski MK, Pache L, Stoneham CA, Yin X, Becker ME, Pratt D, Churas C, Rosenthal SB, Liu S, Weston S, De Jesus PD, O\u2019Neill AM, Gounder AP, Nguyen C, Pu Y, Curry HM, Oom AL, Miorin L, Rodriguez-Frandsen A, Zheng F, Wu C, Xiong Y, Urbanowski M, Shaw ML, Chang MW, Benner C, Hope TJ, Frieman MB, Garc\u00eda-Sastre A, Ideker T, Hultquist JF, Guatelli J, Chanda SK (2021) Functional landscape of sars-cov-2 cellular restriction. Mol Cell 81:2656\u201326688","journal-title":"Mol Cell"},{"key":"1701_CR86","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1038\/bjc.2016.313","volume":"115","author":"L Marzi","year":"2016","unstructured":"Marzi L, Combes E, Vi\u00e9 N, Ayrolles-Torro A, Tosi D, Desigaud D, Perez-Gracia E, Larbouret C, Montagut C, Iglesias M, Jarlier M, Denis V, Linares LK, Lam EW-F, Martineau P, Del Rio M, Gongora C (2016) Foxo3a and the mapk p38 are activated by cetuximab to induce cell death and inhibit cell proliferation and their expression predicts cetuximab efficacy in colorectal cancer. Br J Cancer 115:1223\u20131233","journal-title":"Br J Cancer"},{"key":"1701_CR87","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1038\/s41418-020-00633-7","volume":"27","author":"T Matsuyama","year":"2020","unstructured":"Matsuyama T, Kubli SP, Yoshinaga SK, Pfeffer K, Mak TW (2020) An aberrant stat pathway is central to covid-19. Cell Death Differ 27:3209\u20133225","journal-title":"Cell Death Differ"},{"key":"1701_CR88","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2024.101811","volume":"39","author":"V Mattos Pereira","year":"2024","unstructured":"Mattos Pereira V, Thakar A, Nair S (2024) Targeting irhom2\/adam17 attenuates covid-19-induced cytokine release from cultured lung epithelial cells. Biochemistry and biophysics reports 39:101811","journal-title":"Biochemistry and biophysics reports"},{"key":"1701_CR89","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.606456","volume":"11","author":"C Mazewski","year":"2020","unstructured":"Mazewski C, Perez RE, Fish EN, Platanias LC (2020) Type i interferon (ifn)-regulated activation of canonical and non-canonical signaling pathways. Front Immunol 11:606456","journal-title":"Front Immunol"},{"key":"1701_CR90","doi-asserted-by":"publisher","first-page":"5299","DOI":"10.1128\/MCB.21.16.5299-5305.2001","volume":"21","author":"O Micheau","year":"2001","unstructured":"Micheau O, Lens S, Gaide O, Alevizopoulos K, Tschopp J (2001) Nf-kappab signals induce the expression of c-flip. Mol Cell Biol 21:5299\u2013305","journal-title":"Mol Cell Biol"},{"key":"1701_CR91","doi-asserted-by":"crossref","unstructured":"Miller AL, Strieter RM, Gruber AD, Ho SB, Lukacs NW (2003) Cxcr2 regulates respiratory syncytial virus-induced airway hyperreactivity and mucus overproduction. J Immunol (Baltimore Md 1950) 170:3348\u201356","DOI":"10.4049\/jimmunol.170.6.3348"},{"key":"1701_CR92","doi-asserted-by":"publisher","first-page":"6142","DOI":"10.3390\/ijms24076142","volume":"24","author":"Z Mohd Zawawi","year":"2023","unstructured":"Mohd Zawawi Z, Kalyanasundram J, Mohd Zain R, Thayan R, Basri DF, Yap WB (2023) Prospective roles of tumor necrosis factor-alpha (tnf-$$\\alpha $$) in covid-19: Prognosis, therapeutic and management. Int J Mol Sci 24:6142","journal-title":"Int J Mol Sci"},{"issue":"10","key":"1701_CR93","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.3899\/jrheum.200547","volume":"47","author":"S Mokuda","year":"2020","unstructured":"Mokuda S, Tokunaga T, Masumoto J, Sugiyama E (2020) Angiotensin-converting enzyme 2, a sars-cov-2 receptor, is upregulated by interleukin 6 through stat3 signaling in synovial tissues. J Rheumatol 47(10):1593\u20131595","journal-title":"J Rheumatol"},{"key":"1701_CR94","doi-asserted-by":"crossref","unstructured":"Mukherjee S (2022) Toll-like receptor 4 in covid-19: friend or foe? Future virology. pp 10\u2013221720210249","DOI":"10.2217\/fvl-2021-0249"},{"key":"1701_CR95","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1186\/s13054-020-03120-0","volume":"24","author":"W Ni","year":"2020","unstructured":"Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, Hou C, Wang H, Liu J, Yang D, Xu Y, Cao Z, Gao Z (2020) Role of angiotensin-converting enzyme 2 (ace2) in covid-19. Crit Care (London England) 24:422","journal-title":"Crit Care (London England)"},{"key":"1701_CR96","doi-asserted-by":"publisher","first-page":"54206","DOI":"10.1371\/journal.pone.0054206","volume":"8","author":"VO Okoh","year":"2013","unstructured":"Okoh VO, Felty Q, Parkash J, Poppiti R, Roy D (2013) Reactive oxygen species via redox signaling to pi3k\/akt pathway contribute to the malignant growth of 4-hydroxy estradiol-transformed mammary epithelial cells. PLoS ONE 8:54206","journal-title":"PLoS ONE"},{"key":"1701_CR97","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1007\/s10753-021-01464-5","volume":"44","author":"OA Olajide","year":"2021","unstructured":"Olajide OA, Iwuanyanwu VU, Lepiarz-Raba I, Al-Hindawi AA (2021) Induction of exaggerated cytokine production in human peripheral blood mononuclear cells by a recombinant sars-cov-2 spike glycoprotein s1 and its inhibition by dexamethasone. Inflammation 44:1865\u20131877","journal-title":"Inflammation"},{"key":"1701_CR98","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1007\/s12602-022-09998-2","volume":"15","author":"F Ol\u00edmpio","year":"2023","unstructured":"Ol\u00edmpio F, Andreata-Santos R, Rosa PC, Santos W, Oliveira C, Aimbire F (2023) Lactobacillus rhamnosus restores antiviral signaling and attenuates cytokines secretion from human bronchial epithelial cells exposed to cigarette smoke and infected with sars-cov-2. Probiotics and antimicrobial proteins 15:1513\u20131528","journal-title":"Probiotics and antimicrobial proteins"},{"key":"1701_CR99","doi-asserted-by":"publisher","first-page":"4100","DOI":"10.3390\/molecules24224100","volume":"24","author":"C Ooppachai","year":"2019","unstructured":"Ooppachai C, Limtrakul Dejkriengkraikul P, Yodkeeree S (2019) Dicentrine potentiates tnf-$$\\alpha $$-induced apoptosis and suppresses invasion of a549 lung adenocarcinoma cells via modulation of nf-$$\\kappa $$b and ap-1 activation. Molecules (Basel Switzerland) 24:4100","journal-title":"Molecules (Basel Switzerland)"},{"key":"1701_CR100","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.3389\/fphys.2018.01659","volume":"9","author":"A Palma","year":"2018","unstructured":"Palma A, Jarrah AS, Tieri P, Cesareni G, Castiglione F (2018) Gene regulatory network modeling of macrophage differentiation corroborates the continuum hypothesis of polarization states. Front Physiol 9:1659","journal-title":"Front Physiol"},{"key":"1701_CR101","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1152\/ajplung.00103.2001","volume":"282","author":"M Papp","year":"2002","unstructured":"Papp M, Li X, Zhuang J, Wang R, Uhal BD (2002) Angiotensin receptor subtype at(1) mediates alveolar epithelial cell apoptosis in response to ang ii. American journal of physiology. Lung cellular and molecular physiology 282:713\u20138","journal-title":"Lung cellular and molecular physiology"},{"issue":"3","key":"1701_CR102","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1177\/1721727X15619185","volume":"13","author":"SH Park","year":"2015","unstructured":"Park SH, Choi H-J, Lee SY, Han J-S (2015) Tlr4-mediated irak1 activation induces tnf-$$\\alpha $$ expression via jnk-dependent nf-$$\\kappa $$b activation in human bronchial epithelial cells. European Journal of Inflammation 13(3):183\u2013195","journal-title":"European Journal of Inflammation"},{"key":"1701_CR103","doi-asserted-by":"publisher","first-page":"1009128","DOI":"10.1371\/journal.ppat.1009128","volume":"16","author":"T Patra","year":"2020","unstructured":"Patra T, Meyer K, Geerling L, Isbell TS, Hoft DF, Brien J, Pinto AK, Ray RB, Ray R (2020) Sars-cov-2 spike protein promotes il-6 trans-signaling by activation of angiotensin ii receptor signaling in epithelial cells. PLoS Pathog 16:1009128","journal-title":"PLoS Pathog"},{"key":"1701_CR104","doi-asserted-by":"publisher","first-page":"1001032","DOI":"10.1371\/journal.pcbi.1001032","volume":"6","author":"M Pedicini","year":"2010","unstructured":"Pedicini M, Barren\u00e4s F, Clancy T, Castiglione F, Hovig E, Kanduri K, Santoni D, Benson M (2010) Combining network modeling and gene expression microarray analysis to explore the dynamics of th1 and th2 cell regulation. PLoS Comput Biol 6:1001032","journal-title":"PLoS Comput Biol"},{"key":"1701_CR105","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nri1604","volume":"5","author":"LC Platanias","year":"2005","unstructured":"Platanias LC (2005) Mechanisms of type-i- and type-ii-interferon-mediated signalling. Nat Rev Immunol 5:375\u201386","journal-title":"Nat Rev Immunol"},{"key":"1701_CR106","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1177\/1753425917698032","volume":"23","author":"M Polke","year":"2017","unstructured":"Polke M, Seiler F, Lepper PM, Kamyschnikow A, Langer F, Monz D, Herr C, Bals R, Beisswenger C (2017) Hypoxia and the hypoxia-regulated transcription factor hif-1$$\\alpha $$ suppress the host defence of airway epithelial cells. Innate Immun 23:373\u2013380","journal-title":"Innate Immun"},{"key":"1701_CR107","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","volume":"6","author":"AG Porter","year":"1999","unstructured":"Porter AG, J\u00e4nicke RU (1999) Emerging roles of caspase-3 in apoptosis. Cell Death Differ 6:99\u2013104","journal-title":"Cell Death Differ"},{"key":"1701_CR108","doi-asserted-by":"publisher","first-page":"9932","DOI":"10.1073\/pnas.1913707117","volume":"117","author":"F P\u00fcschel","year":"2020","unstructured":"P\u00fcschel F, Favaro F, Redondo-Pedraza J, Lucendo E, Iurlaro R, Marchetti S, Majem B, Eldering E, Nadal E, Ricci J-E, Chevet E, Mu\u00f1oz-Pinedo C (2020) Starvation and antimetabolic therapy promote cytokine release and recruitment of immune cells. Proc Natl Acad Sci USA 117:9932\u20139941","journal-title":"Proc Natl Acad Sci USA"},{"key":"1701_CR109","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.985363","volume":"12","author":"S Qian","year":"2022","unstructured":"Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J (2022) The role of bcl-2 family proteins in regulating apoptosis and cancer therapy. Front Oncol 12:985363","journal-title":"Front Oncol"},{"key":"1701_CR110","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2019.111737","volume":"386","author":"Q Qiu","year":"2020","unstructured":"Qiu Q, Yang Z, Cao F, Yang C, Hardy P, Yan X, Yang S, Xiong W (2020) Activation of nlrp3 inflammasome by lymphocytic microparticles via tlr4 pathway contributes to airway inflammation. Exp Cell Res 386:111737","journal-title":"Exp Cell Res"},{"key":"1701_CR111","first-page":"00299","volume":"34","author":"S Ramasamy","year":"2021","unstructured":"Ramasamy S, Subbian S (2021) Critical determinants of cytokine storm and type i interferon response in covid-19 pathogenesis. Clin Microbiol Rev 34:00299\u201320","journal-title":"Clin Microbiol Rev"},{"key":"1701_CR112","doi-asserted-by":"publisher","first-page":"02415","DOI":"10.1128\/JVI.02415-20","volume":"95","author":"A Rebendenne","year":"2021","unstructured":"Rebendenne A, Valad\u00e3o ALC, Tauziet M, Maarifi G, Bonaventure B, McKellar J, Plan\u00e8s R, Nisole S, Arnaud-Arnould M, Moncorg\u00e9 O, Goujon C (2021) Sars-cov-2 triggers an mda-5-dependent interferon response which is unable to control replication in lung epithelial cells. J Virol 95:02415\u201320","journal-title":"J Virol"},{"issue":"1","key":"1701_CR113","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s00285-023-01940-6","volume":"87","author":"HA Ribeiro","year":"2023","unstructured":"Ribeiro HA, Scindia Y, Mehrad B, Laubenbacher R (2023) Covid-19-associated pulmonary aspergillosis in immunocompetent patients: a virtual patient cohort study. J Math Biol 87(1):6","journal-title":"J Math Biol"},{"issue":"1","key":"1701_CR114","doi-asserted-by":"publisher","first-page":"2000080","DOI":"10.1371\/journal.pbio.2000080","volume":"15","author":"S Riethmueller","year":"2017","unstructured":"Riethmueller S, Somasundaram P, Ehlers JC, Hung C-W, Flynn CM, Lokau J, Agthe M, D\u00fcsterh\u00f6ft S, Zhu Y, Gr\u00f6tzinger J et al (2017) Proteolytic origin of the soluble human il-6r in vivo and a decisive role of n-glycosylation. PLoS Biol 15(1):2000080","journal-title":"PLoS Biol"},{"key":"1701_CR115","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102683","volume":"122","author":"AI Rodriguez-Perez","year":"2021","unstructured":"Rodriguez-Perez AI, Labandeira CM, Pedrosa MA, Valenzuela R, Suarez-Quintanilla JA, Cortes-Ayaso M, May\u00e1n-Conesa P, Labandeira-Garcia JL (2021) Autoantibodies against ace2 and angiotensin type-1 receptors increase severity of covid-19. J Autoimmun 122:102683","journal-title":"J Autoimmun"},{"key":"1701_CR116","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102420","volume":"24","author":"E Saccon","year":"2021","unstructured":"Saccon E, Chen X, Mikaeloff F, Rodriguez JE, Szekely L, Vinhas BS, Krishnan S, Byrareddy SN, Frisan T, Vegvari A, Mirazimi A, Neogi U, Gupta S (2021) Cell-type-resolved quantitative proteomics map of interferon response against sars-cov-2. IScience 24:102420","journal-title":"IScience"},{"key":"1701_CR117","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1371\/journal.pcbi.0030163","volume":"3","author":"J Saez-Rodriguez","year":"2007","unstructured":"Saez-Rodriguez J, Simeoni L, Lindquist J, Hemenway R, Bommhardt U, Arndt B, Haus U, Weismantel R, Gilles E, Klamt S, Schraven B (2007) A logical model provides insights into t cell receptor signaling. PLoS Comput Biol 3:163","journal-title":"PLoS Comput Biol"},{"key":"1701_CR118","first-page":"003","volume":"6","author":"AR Safa","year":"2013","unstructured":"Safa AR (2013) Roles of c-flip in apoptosis, necroptosis, and autophagy. Journal of carcinogenesis & mutagenesis Suppl 6:003","journal-title":"Journal of carcinogenesis & mutagenesis Suppl"},{"key":"1701_CR119","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3892\/br.2021.1419","volume":"14","author":"AA Salman","year":"2021","unstructured":"Salman AA, Waheed MH, Ali-Abdulsahib AA, Atwan ZW (2021) Low type i interferon response in covid-19 patients: Interferon response may be a potential treatment for covid-19. Biomedical reports 14:43","journal-title":"Biomedical reports"},{"key":"1701_CR120","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/sj.cdd.4401438","volume":"11","author":"M Sawada","year":"2004","unstructured":"Sawada M, Kiyono T, Nakashima S, Shinoda J, Naganawa T, Hara S, Iwama T, Sakai N (2004) Molecular mechanisms of tnf-alpha-induced ceramide formation in human glioma cells: P53-mediated oxidant stress-dependent and -independent pathways. Cell Death Differ 11:997\u20131008","journal-title":"Cell Death Differ"},{"key":"1701_CR121","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1752-0509-1-4","volume":"1","author":"MA Schaub","year":"2007","unstructured":"Schaub MA, Henzinger TA, Fisher J (2007) Qualitative networks: a symbolic approach to analyze biological signaling networks. BMC Syst Biol 1:4","journal-title":"BMC Syst Biol"},{"key":"1701_CR122","doi-asserted-by":"publisher","first-page":"525","DOI":"10.4062\/biomolther.2014.094","volume":"22","author":"H-S Seo","year":"2014","unstructured":"Seo H-S, Sikder MA, Lee HJ, Ryu J, Lee CJ (2014) Apigenin inhibits tumor necrosis factor-$$\\alpha $$-induced production and gene expression of mucin through regulating nuclear factor-kappa b signaling pathway in airway epithelial cells. Biomolecules & therapeutics 22:525\u201331","journal-title":"Biomolecules & therapeutics"},{"key":"1701_CR123","doi-asserted-by":"publisher","first-page":"2365","DOI":"10.1002\/jcp.24409","volume":"228","author":"A Sermeus","year":"2013","unstructured":"Sermeus A, Rebucci M, Fransolet M, Flamant L, Desmet D, Delaive E, Arnould T, Michiels C (2013) Differential effect of hypoxia on etoposide-induced dna damage response and p53 regulation in different cell types. J Cell Physiol 228:2365\u201376","journal-title":"J Cell Physiol"},{"key":"1701_CR124","doi-asserted-by":"publisher","first-page":"4873","DOI":"10.2147\/IJN.S315782","volume":"16","author":"HJ Shin","year":"2021","unstructured":"Shin HJ, Jo MJ, Jin IS, Park C-W, Kim J-S, Shin DH (2021) Optimization and pharmacokinetic evaluation of synergistic fenbendazole and rapamycin co-encapsulated in methoxy poly(ethylene glycol)-$$<$$i$$>$$b$$<$$\/i$$>$$-poly(caprolactone) polymeric micelles. Int J Nanomed 16:4873\u20134889","journal-title":"Int J Nanomed"},{"key":"1701_CR125","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/ptr.4954","volume":"28","author":"MA Sikder","year":"2014","unstructured":"Sikder MA, Lee HJ, Mia MZ, Park SH, Ryu J, Kim J-H, Min SY, Hong J-H, Seok JH, Lee CJ (2014) Inhibition of tnf-$$\\alpha $$-induced muc5ac mucin gene expression and production by wogonin through the inactivation of nf-$$\\kappa $$b signaling in airway epithelial cells. Phytotherapy research PTR 28:62\u20138","journal-title":"Phytotherapy research PTR"},{"key":"1701_CR126","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1074\/jbc.M304736200","volume":"279","author":"C Skurk","year":"2004","unstructured":"Skurk C, Maatz H, Kim H-S, Yang J, Abid MR, Aird WC, Walsh K (2004) The akt-regulated forkhead transcription factor foxo3a controls endothelial cell viability through modulation of the caspase-8 inhibitor flip. J Biol Chem 279:1513\u201325","journal-title":"J Biol Chem"},{"key":"1701_CR127","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1002\/jmv.27317","volume":"94","author":"F Sodeifian","year":"2022","unstructured":"Sodeifian F, Nikfarjam M, Kian N, Mohamed K, Rezaei N (2022) The role of type i interferon in the treatment of covid-19. J Med Virol 94:63\u201381","journal-title":"J Med Virol"},{"key":"1701_CR128","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s42977-021-00092-2","volume":"72","author":"G Stepanova","year":"2021","unstructured":"Stepanova G (2021) Biologia futura: is adam 17 the reason for covid-19 susceptibility in hyperglycemic and diabetic patients? Biologia futura 72:291\u2013297","journal-title":"Biologia futura"},{"issue":"16","key":"1701_CR129","doi-asserted-by":"publisher","first-page":"12878","DOI":"10.14814\/phy2.12878","volume":"4","author":"M Stolarczyk","year":"2016","unstructured":"Stolarczyk M, Amatngalim GD, Yu X, Veltman M, Hiemstra PS, Scholte BJ (2016) Adam 17 and egfr regulate il-6 receptor and amphiregulin mrna expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (copd). Physiol Rep 4(16):12878","journal-title":"Physiol Rep"},{"key":"1701_CR130","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1007\/s10930-020-09935-8","volume":"39","author":"S Suhail","year":"2020","unstructured":"Suhail S, Zajac J, Fossum C, Lowater H, McCracken C, Severson N, Laatsch B, Narkiewicz-Jodko A, Johnson B, Liebau J, Bhattacharyya S, Hati S (2020) Role of oxidative stress on sars-cov (sars) and sars-cov-2 (covid-19) infection: A review. Protein J 39:644\u2013656","journal-title":"Protein J"},{"key":"1701_CR131","doi-asserted-by":"publisher","first-page":"7461","DOI":"10.1073\/pnas.1002459107","volume":"107","author":"S Suzuki","year":"2010","unstructured":"Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, Sugano S, Sato E, Nagao T, Yokote K, Tatsuno I, Prives C (2010) Phosphate-activated glutaminase (gls2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc Natl Acad Sci USA 107:7461\u20136","journal-title":"Proc Natl Acad Sci USA"},{"key":"1701_CR132","doi-asserted-by":"publisher","first-page":"4095","DOI":"10.3390\/ijms23084095","volume":"23","author":"M Tolomeo","year":"2022","unstructured":"Tolomeo M, Cavalli A, Cascio A (2022) Stat1 and its crucial role in the control of viral infections. Int J Mol Sci 23:4095","journal-title":"Int J Mol Sci"},{"key":"1701_CR133","doi-asserted-by":"crossref","unstructured":"Uliczka K, Bossen J, Zissler UM, Fink C, Niu X, Pieper M, Prange RD, Vock C, Wagner C, Knop M et\u00a0al (2024) Foxo factors are essential for maintaining organ homeostasis by acting as stress sensors in airway epithelial cells. bioRxiv, 2024\u201301","DOI":"10.7554\/eLife.96385"},{"key":"1701_CR134","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1093\/jrr\/rrv021","volume":"56","author":"H Ushijima","year":"2015","unstructured":"Ushijima H, Suzuki Y, Oike T, Komachi M, Yoshimoto Y, Ando K, Okonogi N, Sato H, Noda S-E, Saito J-I, Nakano T (2015) Radio-sensitization effect of an mtor inhibitor, temsirolimus, on lung adenocarcinoma a549 cells under normoxic and hypoxic conditions. J Radiat Res 56:663\u20138","journal-title":"J Radiat Res"},{"key":"1701_CR135","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.abb.2014.08.013","volume":"562","author":"RJ Valentine","year":"2014","unstructured":"Valentine RJ, Coughlan KA, Ruderman NB, Saha AK (2014) Insulin inhibits ampk activity and phosphorylates ampk ser485\/491 through akt in hepatocytes, myotubes and incubated rat skeletal muscle. Arch Biochem Biophys 562:62\u20139","journal-title":"Arch Biochem Biophys"},{"key":"1701_CR136","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1042\/BCJ20170097","volume":"474","author":"S Vollmer","year":"2017","unstructured":"Vollmer S, Strickson S, Zhang T, Gray N, Lee KL, Rao VR, Cohen P (2017) The mechanism of activation of irak1 and irak4 by interleukin-1 and toll-like receptor agonists. Biochem J 474:2027\u20132038","journal-title":"Biochem J"},{"key":"1701_CR137","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12890-018-0735-0","volume":"18","author":"W Wang","year":"2018","unstructured":"Wang W, Weng J, Yu L, Huang Q, Jiang Y, Guo X (2018) Role of tlr4-p38 mapk-hsp27 signal pathway in lps-induced pulmonary epithelial hyperpermeability. BMC Pulm Med 18:178","journal-title":"BMC Pulm Med"},{"key":"1701_CR138","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.789180","volume":"11","author":"J Wang","year":"2022","unstructured":"Wang J, Zhao H, An Y (2022) Ace2 shedding and the role in covid-19. Front Cell Infect Microbiol 11:789180","journal-title":"Front Cell Infect Microbiol"},{"key":"1701_CR139","doi-asserted-by":"publisher","first-page":"1059376","DOI":"10.3389\/fimmu.2022.1059376","volume":"13","author":"K Wang","year":"2022","unstructured":"Wang K, Xuan Z, Liu X, Zheng M, Yang C, Wang H (2022) Immunomodulatory role of metalloproteinase adam17 in tumor development. Front Immunol 13:1059376","journal-title":"Front Immunol"},{"key":"1701_CR140","doi-asserted-by":"publisher","first-page":"6371","DOI":"10.3390\/ijms24076371","volume":"24","author":"X Wang","year":"2023","unstructured":"Wang X, Liu Y, Li K, Hao Z (2023) Roles of p53-mediated host-virus interaction in coronavirus infection. Int J Mol Sci 24:6371","journal-title":"Int J Mol Sci"},{"key":"1701_CR141","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176392","volume":"971","author":"X Wang","year":"2024","unstructured":"Wang X, Ma J, Lin D, Bai Y, Zhang D, Jia X, Gao J (2024) Mir-145-5p reduced ang ii-induced ace2 shedding and the inflammatory response in alveolar epithelial cells by targeting adam17 and inhibiting the at1r\/adam17 pathway. Eur J Pharmacol 971:176392","journal-title":"Eur J Pharmacol"},{"key":"1701_CR142","doi-asserted-by":"publisher","first-page":"4300","DOI":"10.1038\/s41467-023-40087-2","volume":"14","author":"H Wei","year":"2023","unstructured":"Wei H, Wang H, Wang G, Qu L, Jiang L, Dai S, Chen X, Zhang Y, Chen Z, Li Y, Guo M, Chen Y (2023) Structures of p53\/bcl-2 complex suggest a mechanism for p53 to antagonize bcl-2 activity. Nat Commun 14:4300","journal-title":"Nat Commun"},{"key":"1701_CR143","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.molcel.2014.11.001","volume":"56","author":"R Weinlich","year":"2014","unstructured":"Weinlich R, Green DR (2014) The two faces of receptor interacting protein kinase-1. Mol Cell 56:469\u201380","journal-title":"Mol Cell"},{"key":"1701_CR144","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1111\/j.1365-2249.2005.02678.x","volume":"139","author":"CK Wong","year":"2005","unstructured":"Wong CK, Wang CB, Ip WK, Tian YP, Lam CWK (2005) Role of p38 mapk and nf-kb for chemokine release in coculture of human eosinophils and bronchial epithelial cells. Clin Exp Immunol 139:90\u2013100","journal-title":"Clin Exp Immunol"},{"key":"1701_CR145","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1165\/rcmb.2009-0120OC","volume":"44","author":"Z Xing","year":"2011","unstructured":"Xing Z, Harper R, Anunciacion J, Yang Z, Gao W, Qu B, Guan Y, Cardona CJ (2011) Host immune and apoptotic responses to avian influenza virus h9n2 in human tracheobronchial epithelial cells. Am J Respir Cell Mol Biol 44:24\u201333","journal-title":"Am J Respir Cell Mol Biol"},{"key":"1701_CR146","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s11010-017-3082-1","volume":"436","author":"S Yadav","year":"2017","unstructured":"Yadav S, Kalra N, Ganju L, Singh M (2017) Activator protein-1 (ap-1): a bridge between life and death in lung epithelial (a549) cells under hypoxia. Mol Cell Biochem 436:99\u2013110","journal-title":"Mol Cell Biochem"},{"key":"1701_CR147","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1038\/s41590-021-00942-0","volume":"22","author":"T Yamada","year":"2021","unstructured":"Yamada T, Sato S, Sotoyama Y, Orba Y, Sawa H, Yamauchi H, Sasaki M, Takaoka A (2021) Rig-i triggers a signaling-abortive anti-sars-cov-2 defense in human lung cells. Nat Immunol 22:820\u2013828","journal-title":"Nat Immunol"},{"key":"1701_CR148","doi-asserted-by":"publisher","first-page":"28383","DOI":"10.1002\/jmv.28383","volume":"95","author":"Q Yang","year":"2023","unstructured":"Yang Q, Tang J, Cao J, Liu F, Fu M, Xue B, Zhou A, Chen S, Liu J, Zhou Y, Shi Y, Peng W, Chen X (2023) Sars-cov-2 infection activates creb\/cbp in cellular cyclic amp-dependent pathways. J Med Virol 95:28383","journal-title":"J Med Virol"},{"key":"1701_CR149","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/sj.cr.7290257","volume":"15","author":"T Zarubin","year":"2005","unstructured":"Zarubin T, Han J (2005) Activation and signaling of the p38 map kinase pathway. Cell Res 15:11\u20138","journal-title":"Cell Res"},{"key":"1701_CR150","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12964-018-0268-4","volume":"16","author":"MM Zegeye","year":"2018","unstructured":"Zegeye MM, Lindkvist M, F\u00e4lker K, Kumawat AK, Paramel G, Greneg\u00e5rd M, Sirsj\u00f6 A, Ljungberg LU (2018) Activation of the jak\/stat3 and pi3k\/akt pathways are crucial for il-6 trans-signaling-mediated pro-inflammatory response in human vascular endothelial cells. Cell Commun Signal 16:55","journal-title":"Cell Commun Signal"},{"key":"1701_CR151","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.virol.2007.04.009","volume":"365","author":"X Zhang","year":"2007","unstructured":"Zhang X, Wu K, Wang D, Yue X, Song D, Zhu Y, Wu J (2007) Nucleocapsid protein of sars-cov activates interleukin-6 expression through cellular transcription factor nf-kappab. Virology 365:324\u201335","journal-title":"Virology"},{"key":"1701_CR152","doi-asserted-by":"publisher","first-page":"16259","DOI":"10.1073\/pnas.1113884108","volume":"108","author":"C Zhang","year":"2011","unstructured":"Zhang C, Lin M, Wu R, Wang X, Yang B, Levine AJ, Hu W, Feng Z (2011) Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the warburg effect. Proc Natl Acad Sci USA 108:16259\u201364","journal-title":"Proc Natl Acad Sci USA"},{"key":"1701_CR153","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.648808","volume":"9","author":"C Zhang","year":"2021","unstructured":"Zhang C, Liu J, Wang J, Zhang T, Xu D, Hu W, Feng Z (2021) The interplay between tumor suppressor p53 and hypoxia signaling pathways in cancer. Frontiers in cell and developmental biology 9:648808","journal-title":"Frontiers in cell and developmental biology"},{"key":"1701_CR154","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3390\/v14040667","volume":"14","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Gargan S, Roche FM, Frieman M, Stevenson NJ (2022) Inhibition of the ifn-$$\\alpha $$ jak\/stat pathway by mers-cov and sars-cov-1 proteins in human epithelial cells. Viruses 14:667","journal-title":"Viruses"},{"key":"1701_CR155","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.778674","volume":"8","author":"Y Zhao","year":"2021","unstructured":"Zhao Y, Liu Y-S (2021) Longevity factor foxo3: A key regulator in aging-related vascular diseases. Frontiers in cardiovascular medicine 8:778674","journal-title":"Frontiers in cardiovascular medicine"},{"key":"1701_CR156","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12943-017-0648-1","volume":"16","author":"Y Zhao","year":"2017","unstructured":"Zhao Y, Hu X, Liu Y, Dong S, Wen Z, He W, Zhang S, Huang Q, Shi M (2017) Ros signaling under metabolic stress: cross-talk between ampk and akt pathway. Mol Cancer 16:79","journal-title":"Mol Cancer"},{"key":"1701_CR157","first-page":"36","volume":"33","author":"F Zheng","year":"2014","unstructured":"Zheng F, Tang Q, Wu J, Zhao S, Liang Z, Li L, Wu W, Hann S (2014) p38$$\\alpha $$ mapk-mediated induction and interaction of foxo3a and p53 contribute to the inhibited-growth and induced-apoptosis of human lung adenocarcinoma cells by berberine. Journal of experimental & clinical cancer research CR 33:36","journal-title":"Journal of experimental & clinical cancer research CR"},{"key":"1701_CR158","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.imlet.2021.06.008","volume":"237","author":"Y Zhou","year":"2021","unstructured":"Zhou Y, Wang M, Li Y, Wang P, Zhao P, Yang Z, Wang S, Zhang L, Li Z, Jia K, Zhong C, Li N, Yu Y, Hou J (2021) Sars-cov-2 spike protein enhances ace2 expression via facilitating interferon effects in bronchial epithelium. Immunol Lett 237:33\u201341","journal-title":"Immunol Lett"},{"key":"1701_CR159","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.708263","volume":"11","author":"Z Zhu","year":"2021","unstructured":"Zhu Z, Zheng Z, Liu J (2021) Comparison of covid-19 and lung cancer $$<$$i$$>$$via$$<$$\/i$$>$$ reactive oxygen species signaling. Front Oncol 11:708263","journal-title":"Front Oncol"},{"key":"1701_CR160","doi-asserted-by":"publisher","first-page":"202200234","DOI":"10.1002\/cmdc.202200234","volume":"17","author":"Z Zhu","year":"2022","unstructured":"Zhu Z, Zhou H, Chen F, Deng J, Yin L, He B, Hu Q, Wang T (2022) Sinomenine derivatives: Synthesis, antitumor activity, and apoptotic induction in mcf-7 cells via il-6\/pi3k\/akt\/nf-$$\\kappa $$b signaling pathway. ChemMedChem 17:202200234","journal-title":"ChemMedChem"},{"key":"1701_CR161","first-page":"51","volume":"80","author":"JE Ziello","year":"2007","unstructured":"Ziello JE, Jovin IS, Huang Y (2007) Hypoxia-inducible factor (hif)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med 80:51\u201360","journal-title":"Yale J Biol Med"}],"container-title":["Bulletin of Mathematical Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11538-026-01701-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11538-026-01701-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11538-026-01701-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:02:14Z","timestamp":1791468134000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11538-026-01701-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":161,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["1701"],"URL":"https:\/\/doi.org\/10.1007\/s11538-026-01701-8","relation":{},"ISSN":["0092-8240","1522-9602"],"issn-type":[{"value":"0092-8240","type":"print"},{"value":"1522-9602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]},"assertion":[{"value":"15 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The model was implemented in Java, and the code can be found at","order":2,"name":"Ethics","label":"Code availability","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"171"}}