{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:02:19Z","timestamp":1779800539998,"version":"3.53.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Protein J"],"DOI":"10.1007\/s10930-025-10317-1","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:19:19Z","timestamp":1768483159000},"page":"400-408","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SARS-CoV-2 Spike Protein S2 Subunit: Recombinant Protein Expression Analysis, Purification, and Its Regulatory Effect on IGF-1R Expression"],"prefix":"10.1007","volume":"45","author":[{"given":"Ekta","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajnish","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishita","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudita","family":"Tripathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Kumari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Prakash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"10317_CR1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMOA2001017","volume":"382","author":"N Zhu","year":"2020","unstructured":"Zhu N, Zhang D, Wang W, Li X, Yang B, Song J et al (2020) A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 382:727\u2013733. https:\/\/doi.org\/10.1056\/NEJMOA2001017","journal-title":"N Engl J Med"},{"key":"10317_CR2","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1136\/postgradmedj-2020-138386","volume":"97","author":"MT Adil","year":"2021","unstructured":"Adil MT, Rahman R, Whitelaw D, Jain V, Al-Taan O, Rashid F et al (2021) SARS-CoV-2 and the pandemic of COVID-19. Postgrad Med J 97:110\u2013116. https:\/\/doi.org\/10.1136\/postgradmedj-2020-138386","journal-title":"Postgrad Med J"},{"key":"10317_CR3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s40249-021-00853-0","volume":"10","author":"AR Zhang","year":"2021","unstructured":"Zhang AR, Shi WQ, Liu K, Li XL, Liu MJ, Zhang WH et al (2021) Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012\u20132020. Infect Dis Poverty 10:66. https:\/\/doi.org\/10.1186\/s40249-021-00853-0","journal-title":"Infect Dis Poverty"},{"key":"10317_CR4","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41579-022-00713-0","volume":"20","author":"MM Lamers","year":"2022","unstructured":"Lamers MM, Haagmans BL (2022) SARS-CoV-2 pathogenesis. Nat Rev Microbiol 20:270\u2013284. https:\/\/doi.org\/10.1038\/s41579-022-00713-0","journal-title":"Nat Rev Microbiol"},{"key":"10317_CR5","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.biochi.2020.09.018","volume":"179","author":"S Muralidar","year":"2020","unstructured":"Muralidar S, Ambi SV, Sekaran S, Krishnan UM (2020) The emergence of COVID-19 as a global pandemic: understanding the epidemiology, immune response and potential therapeutic targets of SARS-CoV-2. Biochimie 179:85\u2013100. https:\/\/doi.org\/10.1016\/j.biochi.2020.09.018","journal-title":"Biochimie"},{"key":"10317_CR6","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1515\/mr-2022-0016","volume":"2","author":"N Zhang","year":"2022","unstructured":"Zhang N, Wang S, Wong CCL (2022) Proteomics research of SARS-CoV-2 and COVID-19 disease. Med Rev (Berl) 2:427\u2013445. https:\/\/doi.org\/10.1515\/mr-2022-0016","journal-title":"Med Rev (Berl)"},{"key":"10317_CR7","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","volume":"181","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann M, Kleine-Weber H, Schroeder S, Kr\u00fcger N, Herrler T, Erichsen S et al (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271\u2013280. https:\/\/doi.org\/10.1016\/j.cell.2020.02.052","journal-title":"Cell"},{"key":"10317_CR8","doi-asserted-by":"publisher","first-page":"3618","DOI":"10.1038\/s41467-020-17371-6","volume":"11","author":"X Fan","year":"2020","unstructured":"Fan X, Cao D, Kong L, Zhang X (2020) Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein. Nat Commun 11:3618. https:\/\/doi.org\/10.1038\/s41467-020-17371-6","journal-title":"Nat Commun"},{"key":"10317_CR9","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/s41564-022-01155-3","volume":"7","author":"X Sun","year":"2022","unstructured":"Sun X, Yi C, Zhu Y, Ding L, Xia S, Chen X et al (2022) Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2. Nat Microbiol 7:1063\u20131074. https:\/\/doi.org\/10.1038\/s41564-022-01155-3","journal-title":"Nat Microbiol"},{"key":"10317_CR10","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","volume":"181","author":"AC Walls","year":"2020","unstructured":"Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181:281\u201392.e6. https:\/\/doi.org\/10.1016\/j.cell.2020.02.058","journal-title":"Cell"},{"key":"10317_CR11","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/s41586-020-2798-3","volume":"586","author":"F Krammer","year":"2020","unstructured":"Krammer F (2020) SARS-CoV-2 vaccines in development. Nature 586:516\u2013527. https:\/\/doi.org\/10.1038\/s41586-020-2798-3","journal-title":"Nature"},{"key":"10317_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012383","volume":"20","author":"J Guenthoer","year":"2024","unstructured":"Guenthoer J, Garrett ME, Lilly M, Depierreux DM, Ruiz F, Chi M et al (2024) The S2 subunit of spike encodes diverse targets for functional antibody responses to SARS-CoV-2. PLoS Pathog 20:e1012383. https:\/\/doi.org\/10.1371\/journal.ppat.1012383","journal-title":"PLoS Pathog"},{"key":"10317_CR13","first-page":"e01232","volume":"98","author":"Z Cai","year":"2024","unstructured":"Cai Z, Ni W, Li W, Wu Z, Yao X, Zheng Y et al (2024) SARS-CoV-2 S protein disrupts the formation of ISGF3 complex through conserved S2 subunit to antagonize type I interferon response. J Virol 98:e01232-e1323","journal-title":"J Virol"},{"key":"10317_CR14","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.virol.2012.09.034","volume":"435","author":"W Hu","year":"2013","unstructured":"Hu W, Chen A, Miao Y, Xia S, Ling Z, Xu K et al (2013) Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Virology 435:320\u2013328. https:\/\/doi.org\/10.1016\/j.virol.2012.09.034","journal-title":"Virology"},{"key":"10317_CR15","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1126\/science.aae0474","volume":"352","author":"R Kong","year":"2016","unstructured":"Kong R, Xu K, Zhou T, Acharya P, Lemmin T, Liu K et al (2016) Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science 352:828\u2013833. https:\/\/doi.org\/10.1126\/science.aae0474","journal-title":"Science"},{"key":"10317_CR16","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1126\/science.aac7263","volume":"349","author":"A Impagliazzo","year":"2015","unstructured":"Impagliazzo A et al (2015) A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science 349:1301\u20131306. https:\/\/doi.org\/10.1126\/science.aac7263","journal-title":"Science"},{"key":"10317_CR17","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.7355","volume":"12","author":"M Pal","year":"2020","unstructured":"Pal M, Berhanu G, Desalegn C, Kandi V (2020) Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): an update. Cureus 12:e7355. https:\/\/doi.org\/10.7759\/cureus.7355","journal-title":"Cureus"},{"key":"10317_CR18","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.cmet.2021.01.016","volume":"33","author":"DJ Drucker","year":"2021","unstructured":"Drucker DJ (2021) Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning. Cell Metab 33:479\u2013498. https:\/\/doi.org\/10.1016\/j.cmet.2021.01.016","journal-title":"Cell Metab"},{"key":"10317_CR19","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/j.coph.2006.10.002","volume":"6","author":"DR Clemmons","year":"2006","unstructured":"Clemmons DR (2006) Involvement of insulin-like growth factor-I in the control of glucose homeostasis. Curr Opin Pharmacol 6:620\u2013625. https:\/\/doi.org\/10.1016\/j.coph.2006.10.002","journal-title":"Curr Opin Pharmacol"},{"key":"10317_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(SICI)1097-4652(200004)183:1","volume":"183","author":"A Grimberg","year":"2000","unstructured":"Grimberg A, Cohen P (2000) Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 183:1\u20139. https:\/\/doi.org\/10.1002\/(SICI)1097-4652(200004)183:1","journal-title":"J Cell Physiol"},{"key":"10317_CR21","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1210\/jc.2003-031140","volume":"89","author":"HL Simpson","year":"2004","unstructured":"Simpson HL, Jackson NC, Shojaee-Moradie F, Jones RH, Russell-Jones DL, S\u00f6nksen PH et al (2004) Insulin-like growth factor I has a direct effect on glucose and protein metabolism, but no effect on lipid metabolism in type 1 diabetes. J Clin Endocrinol Metab 89:425\u2013432. https:\/\/doi.org\/10.1210\/jc.2003-031140","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"10317_CR22","doi-asserted-by":"publisher","first-page":"463","DOI":"10.18632\/oncotarget.886","volume":"4","author":"F Janku","year":"2013","unstructured":"Janku F, Huang HJ, Angelo LS, Kurzrock R (2013) A kinase-independent biological activity for insulin growth factor-1 receptor (IGF-1R): implications for inhibition of the IGF-1R signal. Oncotarget 4(3):463\u2013473","journal-title":"Oncotarget"},{"key":"10317_CR23","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.796991","volume":"9","author":"E Tan","year":"2021","unstructured":"Tan E, Chin CSH, Lim ZFS, Ng SK (2021) HEK293 cell line as a platform to produce recombinant proteins and viral vectors. Front Bioeng Biotechnol 9:796991","journal-title":"Front Bioeng Biotechnol"},{"issue":"2","key":"10317_CR24","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3934\/publichealth.2017.2.127","volume":"4","author":"SJ Olshansky","year":"2017","unstructured":"Olshansky SJ, Hayflick L (2017) The role of the WI-38 cell strain in saving lives and reducing morbidity. AIMS Public Health 4(2):127\u2013137","journal-title":"AIMS Public Health"},{"key":"10317_CR25","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1007\/s11033-018-4298-1","volume":"45","author":"KM Santosh","year":"2018","unstructured":"Santosh KM, Nitish K, Gautam K, Tara K, Krishna P (2018) Recombinant human interferon regulatory factor-1 (IRF-1) protein expression and solubilisation study in Escherichia coli. Mol Biol Rep 45:1367\u20131374. https:\/\/doi.org\/10.1007\/s11033-018-4298-1","journal-title":"Mol Biol Rep"},{"key":"10317_CR26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.pep.2016.06.009","volume":"130","author":"WC Tsai","year":"2017","unstructured":"Tsai WC, Wu TC, Chiang BL, Wen HW (2017) Cloning, expression, and purification of recombinant major mango allergen Man i 1 in Escherichia coli. Protein Expr Purif 130:35\u201343. https:\/\/doi.org\/10.1016\/j.pep.2016.06.009","journal-title":"Protein Expr Purif"},{"issue":"9","key":"10317_CR27","doi-asserted-by":"publisher","first-page":"429","DOI":"10.4103\/1947-2714.100998","volume":"4","author":"T Mahmood","year":"2012","unstructured":"Mahmood T, Yang P-C (2012) Western blot: technique, theory, and trouble shooting. North Am J Med Sci 4(9):429","journal-title":"North Am J Med Sci"},{"key":"10317_CR28","doi-asserted-by":"publisher","first-page":"3824","DOI":"10.1038\/s41467-022-31615-7","volume":"13","author":"JB Case","year":"2022","unstructured":"Case JB, Mackin S, Errico JM, Chong Z, Madden EA, Whitener B et al (2022) Resilience of S309 and AZD7442 monoclonal antibody treatments against infection by SARS-CoV-2 Omicron lineage strains. Nat Commun 13:3824. https:\/\/doi.org\/10.1038\/s41467-022-31615-7","journal-title":"Nat Commun"},{"key":"10317_CR29","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s12038-011-9180-4","volume":"37","author":"A Gupta","year":"2012","unstructured":"Gupta A, Rath PC (2012) Expression, purification and characterization of the interferon-inducible, antiviral and tumour-suppressor protein, human RNase L. J Biosci 37:103\u2013113. https:\/\/doi.org\/10.1007\/s12038-011-9180-4","journal-title":"J Biosci"},{"key":"10317_CR30","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1002\/pro.102","volume":"18","author":"A Sivashanmugam","year":"2009","unstructured":"Sivashanmugam A, Murray V, Cui C, Zhang Y, Wang J, Li Q (2009) Practical protocols for production of very high yields of recombinant proteins using Escherichia coli. Protein Sci 18:936\u2013948. https:\/\/doi.org\/10.1002\/pro.102","journal-title":"Protein Sci"},{"key":"10317_CR31","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-7-671","volume":"7","author":"AL Larentis","year":"2014","unstructured":"Larentis AL, Nicolau JFMQ, Esteves GDS, Vareschini DT, De Almeida FVR, Dos Reis MG et al (2014) Evaluation of pre-induction temperature, cell growth at induction and IPTG concentration on the expression of a leptospiral protein in E. coli using shaking flasks and microbioreactor. BMC Res Notes 7:671. https:\/\/doi.org\/10.1186\/1756-0500-7-671","journal-title":"BMC Res Notes"},{"key":"10317_CR32","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41419-018-0536-z","volume":"9","author":"SH Jeon","year":"2018","unstructured":"Jeon SH, Yoo JK, Kim CM, Lim ES, Lee SJ, Lee JM et al (2018) The novel hsa-miR-12528 regulates tumourigenesis and metastasis through hypo-phosphorylation of AKT cascade by targeting IGF-1R in human lung cancer. Cell Death Dis 9:493. https:\/\/doi.org\/10.1038\/s41419-018-0536-z","journal-title":"Cell Death Dis"},{"key":"10317_CR33","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1002\/ijc.32118","volume":"145","author":"A De Vincenzo","year":"2019","unstructured":"De Vincenzo A, Belli S, Franco P, Telesca M, Iaccarino I, Botti G et al (2019) Paracrine recruitment and activation of fibroblasts by c-Myc expressing breast epithelial cells through the IGFs\/IGF-1R axis. Int J Cancer 145:2827\u20132839. https:\/\/doi.org\/10.1002\/ijc.32118","journal-title":"Int J Cancer"},{"key":"10317_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155236","volume":"133","author":"J Shin","year":"2022","unstructured":"Shin J, Toyoda S, Nishitani S, Onodera T, Fukuda S, Kita S et al (2022) SARS-CoV-2 infection impairs the insulin\/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1. Metabolism 133:155236. https:\/\/doi.org\/10.1016\/j.metabol.2022.155236","journal-title":"Metabolism"},{"key":"10317_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2021.166260","volume":"1867","author":"F Li","year":"2021","unstructured":"Li F, Li J, Wang PH, Yang N, Huang J, Ou J et al (2021) SARS-CoV-2 spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K\/AKT\/mTOR signaling. Biochim Biophys Acta Mol Basis Dis 1867:166260. https:\/\/doi.org\/10.1016\/j.bbadis.2021.166260","journal-title":"Biochim Biophys Acta Mol Basis Dis"}],"container-title":["The Protein Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10930-025-10317-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10930-025-10317-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10930-025-10317-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T12:02:51Z","timestamp":1779796971000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10930-025-10317-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["10317"],"URL":"https:\/\/doi.org\/10.1007\/s10930-025-10317-1","relation":{},"ISSN":["1875-8355"],"issn-type":[{"value":"1875-8355","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]},"assertion":[{"value":"18 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}