{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T01:18:07Z","timestamp":1785806287693,"version":"3.56.0"},"reference-count":140,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:p>Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Following initial infection of airway epithelia, SARS-CoV-2 invades a wide range of cells in multiple organs, including pancreatic islet cells. Diabetes is now recognised as a risk factor for severe COVID-19 outcomes, including hospitalisation and death. Additionally, COVID-19 is associated with a higher risk of new-onset diabetes and metabolic complications of diabetes. One mechanism by which these deleterious outcomes may occur is via the destruction of insulin-producing islet \u03b2 cells, either directly by SARS-CoV-2 entry into \u03b2 cells or indirectly due to inflammation and fibrosis in the surrounding microenvironment. While the canonical pathway of viral entry via angiotensin-converting enzyme 2 (ACE2) has been established as a major route of SARS-CoV-2 infection in the lung, it may not be solely responsible for viral entry into the endocrine pancreas. This is likely due to the divergent expression of viral entry factors among different tissues. For example, expression of ACE2 has not been unequivocally demonstrated in \u03b2 cells. Thus, it is important to understand how other proteins known to be highly expressed in pancreatic endocrine cells may be involved in SARS-CoV-2 entry, with the view that these could be targeted to prevent the demise of the \u03b2 cell in COVID-19. To that end, this review discusses alternate receptors of SARS-CoV-2 (CD147 and GRP78), as well as mediators (furin, TMPRSS2, cathepsin L, ADAM17, neuropilin-1, and heparan sulphate) that may facilitate SARS-CoV-2 entry into pancreatic islets independent of or in conjunction with ACE2.<\/jats:p>","DOI":"10.1530\/jme-21-0282","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T08:26:59Z","timestamp":1651825619000},"page":"R63-R79","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":19,"title":["Going viral in the islet: mediators of SARS-CoV-2 entry beyond ACE2"],"prefix":"10.1530","volume":"69","author":[{"given":"Rohita","family":"Rangu","sequence":"first","affiliation":[{"name":"Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA"},{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pandora L","family":"Wander","sequence":"additional","affiliation":[{"name":"Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA"},{"name":"Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breanne M","family":"Barrow","sequence":"additional","affiliation":[{"name":"Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4831-7034","authenticated-orcid":true,"given":"Sakeneh","family":"Zraika","sequence":"additional","affiliation":[{"name":"Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA"},{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Diabetes","doi-asserted-by":"publisher","first-page":"3034","DOI":"10.2337\/db07-1802","article-title":"Cytokine-induced \u03b2-cell death is independent of endoplasmic reticulum stress signaling","volume":"57","author":"\u00c5kerfeldt","year":"2008","unstructured":"\u00c5kerfeldt MCHowes JChan JYStevens VABoubenna NMcGuire HMKing CBiden TJLaybutt DR2008Cytokine-induced \u03b2-cell death is independent of endoplasmic reticulum stress signaling. Diabetes573034\u20133044. (https:\/\/doi.org\/10.2337\/db07-1802)10.2337\/db07-1802"},{"key":"bib2","series-title":"Nature","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41586-021-03553-9","article-title":"High-dimensional characterization of post-acute sequelae of COVID-19","volume":"594","author":"Al-Aly","year":"2021","unstructured":"Al-Aly ZXie YBowe B2021High-dimensional characterization of post-acute sequelae of COVID-19. Nature594259\u2013264. (https:\/\/doi.org\/10.1038\/s41586-021-03553-9)10.1038\/s41586-021-03553-9"},{"key":"bib3","series-title":"Cell Death and Differentiation","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1038\/cdd.2012.67","article-title":"C\/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in \u03b2-cells","volume":"19","author":"Allagnat","year":"2012","unstructured":"Allagnat FFukaya MNogueira TCDelaroche DWelsh NMarselli LMarchetti PHaefliger JAEizirik DLCardozo AK2012C\/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in \u03b2-cells. Cell Death and Differentiation191836\u20131846. (https:\/\/doi.org\/10.1038\/cdd.2012.67)10.1038\/cdd.2012.67"},{"key":"bib4","series-title":"Heliyon","article-title":"Expression profiles of the SARS-CoV-2 host invasion genes in nasopharyngeal and oropharyngeal swabs of COVID-19 patients","volume":"6","author":"Amati","year":"2020","unstructured":"Amati FVancheri CLatini AColona VLGrelli SD\u2019Apice MRBalestrieri EPassarelli CMinutolo ALoddo S, 2020Expression profiles of the SARS-CoV-2 host invasion genes in nasopharyngeal and oropharyngeal swabs of COVID-19 patients. Heliyon6 e05143. (https:\/\/doi.org\/10.1016\/j.heliyon.2020.e05143)"},{"key":"bib5","series-title":"eLife","article-title":"SARS-CoV-2 strategically mimics proteolytic activation of human ENaC","volume":"9","author":"Anand","year":"2020","unstructured":"Anand PPuranik AAravamudan MVenkatakrishnan AJSoundararajan V2020SARS-CoV-2 strategically mimics proteolytic activation of human ENaC. eLife9 e58603. (https:\/\/doi.org\/10.7554\/eLife.58603)"},{"key":"bib6","series-title":"Frontiers in Pharmacology","article-title":"Pathological aspects of COVID-19 as a conformational disease and the use of pharmacological chaperones as a potential therapeutic strategy","volume":"11","author":"Aoe","year":"2020","unstructured":"Aoe T2020Pathological aspects of COVID-19 as a conformational disease and the use of pharmacological chaperones as a potential therapeutic strategy. Frontiers in Pharmacology11 1095. (https:\/\/doi.org\/10.3389\/fphar.2020.01095)"},{"key":"bib7","series-title":"Cells","article-title":"The PIKfyve inhibitor apilimod: a double-edged sword against COVID-19","volume":"10","author":"Baranov","year":"2020","unstructured":"Baranov MVBianchi Fvan den Bogaart G2020The PIKfyve inhibitor apilimod: a double-edged sword against COVID-19. Cells10 30. (https:\/\/doi.org\/10.3390\/cells10010030)"},{"key":"bib8","series-title":"Signal Transduction and Targeted Therapy","article-title":"Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial","volume":"6","author":"Bian","year":"2021","unstructured":"Bian HZheng ZHWei DWen AZhang ZLian JQKang WZHao CQWang JXie RH2021Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial. Signal Transduction and Targeted Therapy6 194. (https:\/\/doi.org\/10.1038\/s41392-021-00603-6)"},{"key":"bib9","series-title":"Diabetes","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.2337\/db16-1318","article-title":"Neprilysin is required for angiotensin-(1\u20137)\u2019s ability to enhance insulin secretion via its proteolytic activity to generate angiotensin-(1-2)","volume":"66","author":"Brar","year":"2017","unstructured":"Brar GSBarrow BMWatson MGriesbach RChoung EWelch ARuzsicska BRaleigh DPZraika S2017Neprilysin is required for angiotensin-(1\u20137)\u2019s ability to enhance insulin secretion via its proteolytic activity to generate angiotensin-(1-2). Diabetes662201\u20132212. (https:\/\/doi.org\/10.2337\/db16-1318)10.2337\/db16-1318"},{"key":"bib10","series-title":"Diabetes","doi-asserted-by":"publisher","first-page":"492","DOI":"10.2337\/db20-0474","article-title":"Loss of furin in \u03b2 cells induces an mTORC1-ATF4 anabolic pathway that leads to \u03b2-cell dysfunction","volume":"70","author":"Brouwers","year":"2021","unstructured":"Brouwers BCoppola IVints KDislich BJouvet NVan Lommel LSegers CGounko NVThorrez LSchuit F, 2021Loss of furin in \u03b2 cells induces an mTORC1-ATF4 anabolic pathway that leads to \u03b2-cell dysfunction. Diabetes70492\u2013503. (https:\/\/doi.org\/10.2337\/db20-0474)10.2337\/db20-0474"},{"key":"bib11","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1007\/s00125-015-3669-6","article-title":"Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms","volume":"58","author":"Brozzi","year":"2015","unstructured":"Brozzi FNardelli TRLopes MMillard IBarthson JIgoillo-Esteve MGrieco FAVillate OOliveira JMCasimir M, 2015Cytokines induce endoplasmic reticulum stress in human, rat and mouse beta cells via different mechanisms. Diabetologia582307\u20132316. (https:\/\/doi.org\/10.1007\/s00125-015-3669-6)10.1007\/s00125-015-3669-6"},{"key":"bib12","series-title":"Molecular and Cellular Endocrinology","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.mce.2018.01.019","article-title":"DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes","volume":"473","author":"Bugliani","year":"2018","unstructured":"Bugliani MSyed FPaula FMMOmar BASuleiman MMossuto SGrano FCardarelli FBoggi UVistoli F2018DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes. Molecular and Cellular Endocrinology473186\u2013193. (https:\/\/doi.org\/10.1016\/j.mce.2018.01.019)10.1016\/j.mce.2018.01.019"},{"key":"bib13","series-title":"International Journal of Molecular Sciences","article-title":"Does the SARS-CoV-2 spike protein receptor binding domain interact effectively with the DPP4 (CD26) receptor? A molecular docking study","volume":"22","author":"Cameron","year":"2021","unstructured":"Cameron KRozano LFalasca MMancera RL2021Does the SARS-CoV-2 spike protein receptor binding domain interact effectively with the DPP4 (CD26) receptor? A molecular docking study. International Journal of Molecular Sciences22 7001. (https:\/\/doi.org\/10.3390\/ijms22137001)"},{"key":"bib14","series-title":"Science","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1126\/science.abd2985","article-title":"Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity","volume":"370","author":"Cantuti-Castelvetri","year":"2020","unstructured":"Cantuti-Castelvetri LOjha RPedro LDDjannatian MFranz JKuivanen Svan der Meer FKallio KKaya TAnastasina M, 2020Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science370856\u2013860. (https:\/\/doi.org\/10.1126\/science.abd2985)10.1126\/science.abd2985"},{"key":"bib15","series-title":"Diabetes","article-title":"Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic \u03b2-cells","volume":"54","author":"Cardozo","year":"2005","unstructured":"Cardozo AKOrtis FStorling JFeng YMRasschaert JTonnesen MVan Eylen FMandrup-Poulsen THerchuelz AEizirik DL2005Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic \u03b2-cells. Diabetes54 452 LP\u2013461 LP. (https:\/\/doi.org\/10.2337\/diabetes.54.2.452)"},{"key":"bib16","series-title":"Journal of Biological Chemistry","article-title":"The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection","volume":"296","author":"Carlos","year":"2021","unstructured":"Carlos AJHa DPYeh DWVan Krieken RTseng CCZhang PGill PMachida KLee AS2021The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection. Journal of Biological Chemistry296 100759. (https:\/\/doi.org\/10.1016\/j.jbc.2021.100759)"},{"key":"bib17","series-title":"Journal of Virology","doi-asserted-by":"publisher","first-page":"9279","DOI":"10.1128\/JVI.00659-06","article-title":"Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein","volume":"80","author":"Chan","year":"2006","unstructured":"Chan CPSiu KLChin KTYuen KYZheng BJin DYChing-Ping CKam-Leung SKing-Tung CKwok-Yung Y2006Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein. Journal of Virology809279\u20139287. (https:\/\/doi.org\/10.1128\/JVI.00659-06)10.1128\/JVI.00659-06"},{"key":"bib18","series-title":"American Journal of Pathology","doi-asserted-by":"publisher","first-page":"2986","DOI":"10.2353\/ajpath.2010.090665","article-title":"TMPRSS2, a serine protease expressed in the prostate on the apical surface of luminal epithelial cells and released into semen in prostasomes, is misregulated in prostate cancer cells","volume":"176","author":"Chen","year":"2010","unstructured":"Chen YWLee MSLucht AChou FPHuang WHavighurst TCKim KWang JKAntalis TMJohnson MD, 2010TMPRSS2, a serine protease expressed in the prostate on the apical surface of luminal epithelial cells and released into semen in prostasomes, is misregulated in prostate cancer cells. American Journal of Pathology1762986\u20132996. (https:\/\/doi.org\/10.2353\/ajpath.2010.090665)10.2353\/ajpath.2010.090665"},{"key":"bib19","series-title":"Journal of Biological Chemistry","doi-asserted-by":"publisher","first-page":"11709","DOI":"10.1074\/jbc.RA118.001897","article-title":"Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells","volume":"293","author":"Chu","year":"2018","unstructured":"Chu HChan CMZhang XWang YYuan SZhou JAu-Yeung RK-HSze KHYang DShuai H, 2018Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells. Journal of Biological Chemistry29311709\u201311726. (https:\/\/doi.org\/10.1074\/jbc.RA118.001897)10.1074\/jbc.RA118.001897"},{"key":"bib20","series-title":"Lancet","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/S0140-6736(97)11212-0","article-title":"Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus","volume":"351","author":"Claas","year":"1998","unstructured":"Claas ECJOsterhaus ADMEvan Beek RDe Jong JCRimmelzwaan GFSenne DAKrauss SShortridge KFWebster RG1998Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet351472\u2013477. (https:\/\/doi.org\/10.1016\/S0140-6736(9711212-0)10.1016\/S0140-6736(97)11212-0"},{"key":"bib21","series-title":"Cell","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.cell.2020.09.033","article-title":"SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2","volume":"183","author":"Clausen","year":"2020","unstructured":"Clausen TMSandoval DRSpliid CBPihl JPerrett HRPainter CDNarayanan AMajowicz SAKwong EMMcVicar RN2020SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2. Cell1831043.e15\u20131057.e15. (https:\/\/doi.org\/10.1016\/j.cell.2020.09.033)10.1016\/j.cell.2020.09.033"},{"key":"bib22","series-title":"Cell Metabolism","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.cmet.2020.11.006","article-title":"SARS-CoV-2 cell entry factors ACE2 and TMPRSS2 are expressed in the microvasculature and ducts of human pancreas but are not enriched in \u03b2 cells","volume":"32","author":"Coate","year":"2020","unstructured":"Coate KCCha JShrestha SWang WGon\u00e7alves LMAlma\u00e7a JKapp MEFasolino MMorgan ADai C2020SARS-CoV-2 cell entry factors ACE2 and TMPRSS2 are expressed in the microvasculature and ducts of human pancreas but are not enriched in \u03b2 cells. Cell Metabolism321028.e4\u20131040.e4. (https:\/\/doi.org\/10.1016\/j.cmet.2020.11.006)10.1016\/j.cmet.2020.11.006"},{"key":"bib23","series-title":"Antiviral Research","article-title":"The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade","volume":"176","author":"Coutard","year":"2020","unstructured":"Coutard BValle Cde Lamballerie XCanard BSeidah NGDecroly E2020The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Research176 104742. (https:\/\/doi.org\/10.1016\/j.antiviral.2020.104742)"},{"key":"bib24","series-title":"Science","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1126\/science.abd3072","article-title":"Neuropilin-1 is a host factor for SARS-CoV-2 infection","volume":"370","author":"Daly","year":"2020","unstructured":"Daly JLSimonetti BKlein KChen KEWilliamson MKAnt\u00f3n-Pl\u00e1garo CShoemark DKSim\u00f3n-Gracia LBauer MHollandi R2020Neuropilin-1 is a host factor for SARS-CoV-2 infection. Science370861\u2013865. (https:\/\/doi.org\/10.1126\/science.abd3072)10.1126\/science.abd3072"},{"key":"bib25","series-title":"Molecules","article-title":"A review of small molecule inhibitors and functional probes of human cathepsin L","volume":"25","author":"Dana","year":"2020","unstructured":"Dana DPathak SK2020A review of small molecule inhibitors and functional probes of human cathepsin L. Molecules25 698. (https:\/\/doi.org\/10.3390\/molecules25030698)"},{"key":"bib26","series-title":"PLoS ONE","article-title":"Heparan sulfate proteoglycans in beta cells provide a critical link between endoplasmic reticulum stress, oxidative stress and type 2 diabetes","volume":"16","author":"Dhounchak","year":"2021","unstructured":"Dhounchak SPopp SKBrown DJLaybutt DRBiden TJBornstein SRParish CRSimeonovic CJ2021Heparan sulfate proteoglycans in beta cells provide a critical link between endoplasmic reticulum stress, oxidative stress and type 2 diabetes. PLoS ONE16 e0252607. (https:\/\/doi.org\/10.1371\/journal.pone.0252607)"},{"key":"bib27","series-title":"Frontiers in Pharmacology","article-title":"SARS-CoV-2 spike-heat shock protein A5 (GRP78) recognition may be related to the immersed human coronaviruses","volume":"11","author":"Elfiky","year":"2020","unstructured":"Elfiky AA2020SARS-CoV-2 spike-heat shock protein A5 (GRP78) recognition may be related to the immersed human coronaviruses. Frontiers in Pharmacology11 577467. (https:\/\/doi.org\/10.3389\/fphar.2020.577467)"},{"key":"bib28","series-title":"Islets","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1080\/19382014.2021.1954458","article-title":"Expression of SARS-CoV-2 receptor \u2018ACE2\u2019 in human pancreatic \u03b2 cells: to be or not to be!","volume":"13","author":"El-Huneidi","year":"2021","unstructured":"El-Huneidi WHamad MTaneera J2021Expression of SARS-CoV-2 receptor \u2018ACE2\u2019 in human pancreatic \u03b2 cells: to be or not to be!Islets13106\u2013114. (https:\/\/doi.org\/10.1080\/19382014.2021.1954458)10.1080\/19382014.2021.1954458"},{"key":"bib29","series-title":"Cells","article-title":"SARS-CoV-2 entry: at the crossroads of CD147 and ACE2","volume":"10","author":"Fenizia","year":"2021","unstructured":"Fenizia CGalbiati SVanetti CVago RClerici MTacchetti CDaniele T2021SARS-CoV-2 entry: at the crossroads of CD147 and ACE2. Cells10 1434. (https:\/\/doi.org\/10.3390\/cells10061434)"},{"key":"bib30","series-title":"Frontiers in Endocrinology","doi-asserted-by":"publisher","first-page":"596898","DOI":"10.3389\/fendo.2020.596898","article-title":"SARS-CoV-2 receptor angiotensin I-converting enzyme type 2 (ACE2) is expressed in human pancreatic \u03b2-cells and in the human pancreas microvasculature","volume":"11","author":"Fignani","year":"2020","unstructured":"Fignani DLicata GBrusco NNigi LGrieco GEMarselli LOverbergh LGysemans CColli MLMarchetti P2020SARS-CoV-2 receptor angiotensin I-converting enzyme type 2 (ACE2) is expressed in human pancreatic \u03b2-cells and in the human pancreas microvasculature. Frontiers in Endocrinology11596898. (https:\/\/doi.org\/10.3389\/fendo.2020.596898)10.3389\/fendo.2020.596898"},{"key":"bib31","series-title":"PNAS","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1073\/pnas.040337597","article-title":"Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expression and antitumor activity","volume":"97","author":"Gagnon","year":"2000","unstructured":"Gagnon MLBielenberg DRGechtman ZMiao HQTakashima SSoker SKlagsbrun M2000Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expression and antitumor activity. PNAS972573\u20132578. (https:\/\/doi.org\/10.1073\/pnas.040337597)10.1073\/pnas.040337597"},{"key":"bib32","series-title":"Signal Transduction and Targeted Therapy","article-title":"CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma","volume":"6","author":"Geng","year":"2021","unstructured":"Geng JChen LYuan YWang KWang YQin CWu GChen RZhang ZWei D2021CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma. Signal Transduction and Targeted Therapy6 347. (https:\/\/doi.org\/10.1038\/s41392-021-00760-8)"},{"key":"bib33","series-title":"Frontiers in Cellular and Infection Microbiology","doi-asserted-by":"publisher","first-page":"589505","DOI":"10.3389\/fcimb.2020.589505","article-title":"Cathepsin L in COVID-19: from pharmacological evidences to genetics","volume":"10","author":"Gomes","year":"2020","unstructured":"Gomes CPFernandes DECasimiro Fda Mata GFPassos MTVarela PMastroianni-Kirsztajn GPesquero JB2020Cathepsin L in COVID-19: from pharmacological evidences to genetics. Frontiers in Cellular and Infection Microbiology10589505. (https:\/\/doi.org\/10.3389\/fcimb.2020.589505)10.3389\/fcimb.2020.589505"},{"key":"bib34","series-title":"Bioscience Reports","article-title":"How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity","volume":"36","author":"Grass","year":"2015","unstructured":"Grass GDToole BP2015How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity. Bioscience Reports36 e00283. (https:\/\/doi.org\/10.1042\/BSR20150256)"},{"key":"bib35","series-title":"Cell Calcium","article-title":"Could an endo-lysosomal ion channel be the Achilles heel of SARS-CoV2?","volume":"88","author":"Grimm","year":"2020","unstructured":"Grimm CTang R2020Could an endo-lysosomal ion channel be the Achilles heel of SARS-CoV2?Cell Calcium88 102212. (https:\/\/doi.org\/10.1016\/j.ceca.2020.102212)"},{"key":"bib36","series-title":"Experimental Lung Research","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1080\/01902140600710512","article-title":"Increased extracellular matrix metalloproteinase inducer (EMMPRIN) expression in pulmonary fibrosis","volume":"32","author":"Guillot","year":"2006","unstructured":"Guillot SDelaval PBrinchault GCaulet-Maugendre SDepince ALena HDelatour BLagente VMartin-Chouly C2006Increased extracellular matrix metalloproteinase inducer (EMMPRIN) expression in pulmonary fibrosis. Experimental Lung Research3281\u201397. (https:\/\/doi.org\/10.1080\/01902140600710512)10.1080\/01902140600710512"},{"key":"bib37","series-title":"Journal of Infection","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.jinf.2020.06.017","article-title":"The stress-inducible molecular chaperone GRP78 as potential therapeutic target for coronavirus infection","volume":"81","author":"Ha","year":"2020","unstructured":"Ha DPVan Krieken RCarlos AJLee AS2020The stress-inducible molecular chaperone GRP78 as potential therapeutic target for coronavirus infection. Journal of Infection81452\u2013482. (https:\/\/doi.org\/10.1016\/j.jinf.2020.06.017)10.1016\/j.jinf.2020.06.017"},{"key":"bib38","series-title":"Antiviral Research","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.antiviral.2009.12.001","article-title":"TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds","volume":"85","author":"Haga","year":"2010","unstructured":"Haga SNagata NOkamura TYamamoto NSata TYamamoto NSasazuki TIshizaka Y2010TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds. Antiviral Research85551\u2013555. (https:\/\/doi.org\/10.1016\/j.antiviral.2009.12.001)10.1016\/j.antiviral.2009.12.001"},{"key":"bib39","series-title":"PNAS","doi-asserted-by":"publisher","first-page":"7809","DOI":"10.1073\/pnas.0711241105","article-title":"Modulation of TNF-\u03b1-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-\u03b1 production and facilitates viral entry","volume":"105","author":"Haga","year":"2008","unstructured":"Haga SYamamoto NNakai-Murakami COsawa YTokunaga KSata TYamamoto NSasazuki TIshizaka Y2008Modulation of TNF-\u03b1-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-\u03b1 production and facilitates viral entry. PNAS1057809\u20137814. (https:\/\/doi.org\/10.1073\/pnas.0711241105)10.1073\/pnas.0711241105"},{"key":"bib40","series-title":"Diabetes Research and Clinical Practice","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1016\/j.diabres.2009.12.016","article-title":"Genetic association of the neuropilin-1 gene with type 1 diabetes in children: neuropilin-1 expression in pancreatic islets","volume":"87","author":"Hasan","year":"2010","unstructured":"Hasan NMKendrick MADruckenbrod NRHuelsmeyer MKWarner TFMacDonald MJ2010Genetic association of the neuropilin-1 gene with type 1 diabetes in children: neuropilin-1 expression in pancreatic islets. Diabetes Research and Clinical Practice87e29\u2013e32. (https:\/\/doi.org\/10.1016\/j.diabres.2009.12.016)10.1016\/j.diabres.2009.12.016"},{"key":"bib41","series-title":"Journal of Biomolecular Structure and Dynamics","first-page":"1","article-title":"Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia","author":"Helal","year":"2020","unstructured":"Helal MAShouman SAbdelwaly AElmehrath AOEssawy MSayed SMSaleh AHEl-Badri N2020Molecular basis of the potential interaction of SARS-CoV-2 spike protein to CD147 in COVID-19 associated-lymphopenia. Journal of Biomolecular Structure and Dynamics1\u201311. (https:\/\/doi.org\/10.1080\/07391102.2020.1822208)"},{"key":"bib42","series-title":"Chemical Science","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1039\/D0SC05064D","article-title":"Molecular mechanism of inhibiting the SARS-CoV-2 cell entry facilitator TMPRSS2 with camostat and nafamostat","volume":"12","author":"Hempel","year":"2021","unstructured":"Hempel TRaich LOlsson SAzouz NPKlingler AMHoffmann MP\u00f6hlmann SRothenberg MENo\u00e9 F2021Molecular mechanism of inhibiting the SARS-CoV-2 cell entry facilitator TMPRSS2 with camostat and nafamostat. Chemical Science12983\u2013992. (https:\/\/doi.org\/10.1039\/D0SC05064D)10.1039\/D0SC05064D"},{"key":"bib43","series-title":"Journal of Virology","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1128\/JVI.02202-13","article-title":"TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein","volume":"88","author":"Heurich","year":"2014","unstructured":"Heurich AHofmann-Winkler HGierer SLiepold TJahn OP\u00f6hlmann S2014TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. Journal of Virology881293\u20131307. (https:\/\/doi.org\/10.1128\/JVI.02202-13)10.1128\/JVI.02202-13"},{"key":"bib44","series-title":"Molecular Systems Biology","article-title":"The protein expression profile of ACE2 in human tissues","volume":"16","author":"Hikmet","year":"2020","unstructured":"Hikmet FM\u00e9ar LEdvinsson \u00c5Micke PUhl\u00e9n MLindskog C2020The protein expression profile of ACE2 in human tissues. Molecular Systems Biology16 e9610. (https:\/\/doi.org\/10.15252\/msb.20209610)"},{"key":"bib45","series-title":"Cell","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020a","unstructured":"Hoffmann MKleine-Weber HSchroeder SKr\u00fcger NHerrler TErichsen SSchiergens TSHerrler GWu NHNitsche A2020aSARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell181271.e8\u2013280.e8. (https:\/\/doi.org\/10.1016\/j.cell.2020.02.052)10.1016\/j.cell.2020.02.052"},{"key":"bib46","series-title":"Molecular Cell","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.molcel.2020.04.022","article-title":"A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells","volume":"78","author":"Hoffmann","year":"2020b","unstructured":"Hoffmann MKleine-Weber HP\u00f6hlmann S2020bA multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Molecular Cell78779.e5\u2013784.e5. (https:\/\/doi.org\/10.1016\/j.molcel.2020.04.022)10.1016\/j.molcel.2020.04.022"},{"key":"bib47","series-title":"EBiomedicine","doi-asserted-by":"publisher","first-page":"103255","DOI":"10.1016\/j.ebiom.2021.103255","article-title":"Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity","volume":"65","author":"Hoffmann","year":"2021","unstructured":"Hoffmann MHofmann-Winkler HSmith JCKr\u00fcger NArora PS\u00f8rensen LKS\u00f8gaard OSHasselstr\u00f8m JBWinkler MHempel T2021Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity. EBiomedicine65103255. (https:\/\/doi.org\/10.1016\/j.ebiom.2021.103255)10.1016\/j.ebiom.2021.103255"},{"key":"bib48","series-title":"Acta Pharmacologica Sinica","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1038\/s41401-020-0485-4","article-title":"Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19","volume":"41","author":"Huang","year":"2020","unstructured":"Huang YYang CXu XFXu WLiu SW2020Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacologica Sinica411141\u20131149. (https:\/\/doi.org\/10.1038\/s41401-020-0485-4)10.1038\/s41401-020-0485-4"},{"key":"bib49","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1007\/s00125-009-1329-4","article-title":"Amyloid formation in human IAPP transgenic mouse islets and pancreas, and human pancreas, is not associated with endoplasmic reticulum stress","volume":"52","author":"Hull","year":"2009","unstructured":"Hull RLZraika SUdayasankar JAston-Mourney KSubramanian SLKahn SE2009Amyloid formation in human IAPP transgenic mouse islets and pancreas, and human pancreas, is not associated with endoplasmic reticulum stress. Diabetologia521102\u20131111. (https:\/\/doi.org\/10.1007\/s00125-009-1329-4)10.1007\/s00125-009-1329-4"},{"key":"bib50","series-title":"Life Sciences","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.lfs.2019.04.022","article-title":"GRP78: a cell\u2019s response to stress","volume":"226","author":"Ibrahim","year":"2019","unstructured":"Ibrahim IMAbdelmalek DHElfiky AA2019GRP78: a cell\u2019s response to stress. Life Sciences226156\u2013163. (https:\/\/doi.org\/10.1016\/j.lfs.2019.04.022)10.1016\/j.lfs.2019.04.022"},{"key":"bib51","series-title":"Journal of Infection","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.jinf.2020.02.026","article-title":"COVID-19 spike-host cell receptor GRP78 binding site prediction","volume":"80","author":"Ibrahim","year":"2020","unstructured":"Ibrahim IMAbdelmalek DHElshahat MEElfiky AA2020COVID-19 spike-host cell receptor GRP78 binding site prediction. Journal of Infection80554\u2013562. (https:\/\/doi.org\/10.1016\/j.jinf.2020.02.026)10.1016\/j.jinf.2020.02.026"},{"key":"bib52","series-title":"Journal of Clinical Medicine","article-title":"Association between nafamostat mesylate and in-hospital mortality in patients with coronavirus disease 2019: a multicenter observational study","volume":"11","author":"Inokuchi","year":"2021","unstructured":"Inokuchi RKuno TKomiyama JUda KMiyamoto YTaniguchi YAbe TIshimaru MAdomi MTamiya N2021Association between nafamostat mesylate and in-hospital mortality in patients with coronavirus disease 2019: a multicenter observational study. Journal of Clinical Medicine11 116. (https:\/\/doi.org\/10.3390\/jcm11010116)"},{"key":"bib53","series-title":"iScience","article-title":"Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1\/S2 site","volume":"23","author":"Jaimes","year":"2020","unstructured":"Jaimes JAMillet JKWhittaker GR2020Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1\/S2 site. iScience23 101212. (https:\/\/doi.org\/10.1016\/j.isci.2020.101212)"},{"key":"bib54","series-title":"International Journal of Molecular Medicine","article-title":"COVID-19 and SARS-CoV-2 host cell entry mediators: expression profiling of TMRSS4 in health and disease","volume":"47","author":"Katopodis","year":"2021","unstructured":"Katopodis PKerslake RDavies JRandeva S HChatha KHall MSpandidos A DAnikin VPolychronis ARobertus L2021COVID-19 and SARS-CoV-2 host cell entry mediators: expression profiling of TMRSS4 in health and disease. International Journal of Molecular Medicine47 64. (https:\/\/doi.org\/10.3892\/ijmm.2021.4897)"},{"key":"bib55","series-title":"Endocrinology","doi-asserted-by":"publisher","first-page":"5126","DOI":"10.1210\/endo.137.11.8895387","article-title":"Developmental expression of proprotein-processing endoprotease furin in rat pancreatic islets","volume":"137","author":"Kayo","year":"1996","unstructured":"Kayo TKonda YTanaka STakata KKoizumi ATakeuchi T1996Developmental expression of proprotein-processing endoprotease furin in rat pancreatic islets. Endocrinology1375126\u20135134. (https:\/\/doi.org\/10.1210\/endo.137.11.8895387)10.1210\/endo.137.11.8895387"},{"key":"bib56","series-title":"Carcinogenesis","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1093\/carcin\/bgs196","article-title":"Hypoxia upregulates CD147 through a combined effect of HIF-1\u03b1 and Sp1 to promote glycolysis and tumor progression in epithelial solid tumors","volume":"33","author":"Ke","year":"2012","unstructured":"Ke XFei FChen YXu LZhang ZHuang QZhang HYang HChen ZXing J2012Hypoxia upregulates CD147 through a combined effect of HIF-1\u03b1 and Sp1 to promote glycolysis and tumor progression in epithelial solid tumors. Carcinogenesis331598\u20131607. (https:\/\/doi.org\/10.1093\/carcin\/bgs196)10.1093\/carcin\/bgs196"},{"key":"bib57","series-title":"Journal of Medical Virology","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1002\/jmv.26397","article-title":"Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells","volume":"93","author":"Ko","year":"2021","unstructured":"Ko MJeon SRyu WSKim S2021Comparative analysis of antiviral efficacy of FDA-approved drugs against SARS-CoV-2 in human lung cells. Journal of Medical Virology931403\u20131408. (https:\/\/doi.org\/10.1002\/jmv.26397)10.1002\/jmv.26397"},{"issue":"Supplement","key":"bib58","series-title":"In Vivo","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.21873\/invivo.11956","article-title":"Endoplasmic reticulum stress markers in SARS-COV-2 infection and pneumonia: case-control study","volume":"34","author":"K\u00f6seler","year":"2020","unstructured":"K\u00f6seler ASabirli RG\u00f6ren TT\u00fcrk\u00e7\u00fcer IKurt \u00d62020Endoplasmic reticulum stress markers in SARS-COV-2 infection and pneumonia: case-control study. In Vivo34 (Supplement) 1645\u20131650. (https:\/\/doi.org\/10.21873\/invivo.11956)10.21873\/invivo.11956"},{"key":"bib59","series-title":"Nature Medicine","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/nm1267","article-title":"A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury","volume":"11","author":"Kuba","year":"2005","unstructured":"Kuba KImai YRao SGao HGuo FGuan BHuan YYang PZhang YDeng W2005A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nature Medicine11875\u2013879. (https:\/\/doi.org\/10.1038\/nm1267)10.1038\/nm1267"},{"key":"bib60","series-title":"Cell Metabolism","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.cmet.2020.11.005","article-title":"Expression of SARS-CoV-2 entry factors in the pancreas of normal organ donors and individuals with COVID-19","volume":"32","author":"Kusmartseva","year":"2020","unstructured":"Kusmartseva IWu WSyed FVan Der Heide VJorgensen MJoseph PTang XCandelario-Jalil EYang CNick H2020Expression of SARS-CoV-2 entry factors in the pancreas of normal organ donors and individuals with COVID-19. Cell Metabolism321041.e6\u20131051.e6. (https:\/\/doi.org\/10.1016\/j.cmet.2020.11.005)10.1016\/j.cmet.2020.11.005"},{"key":"bib61","series-title":"Signal Transduction and Targeted Therapy","article-title":"Not only ACE2 \u2013 the quest for additional host cell mediators of SARS-CoV-2 infection: neuropilin-1 (NRP1) as a novel SARS-CoV-2 host cell entry mediator implicated in COVID-19","volume":"6","author":"Kyrou","year":"2021","unstructured":"Kyrou IRandeva HSSpandidos DAKarteris E2021Not only ACE2 \u2013 the quest for additional host cell mediators of SARS-CoV-2 infection: neuropilin-1 (NRP1) as a novel SARS-CoV-2 host cell entry mediator implicated in COVID-19. Signal Transduction and Targeted Therapy6 21. (https:\/\/doi.org\/10.1038\/s41392-020-00460-9)"},{"key":"bib62","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1007\/s00125-006-0590-z","article-title":"Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes","volume":"50","author":"Laybutt","year":"2007","unstructured":"Laybutt DRPreston AM\u00c5kerfeldt MCKench JGBusch AKBiankin AVBiden TJ2007Endoplasmic reticulum stress contributes to beta cell apoptosis in type 2 diabetes. Diabetologia50752\u2013763. (https:\/\/doi.org\/10.1007\/s00125-006-0590-z)10.1007\/s00125-006-0590-z"},{"key":"bib63","series-title":"Endocrinology","article-title":"Endocrine significance of SARS-CoV-2\u2019s reliance on ACE2","volume":"161","author":"Lazartigues","year":"2020","unstructured":"Lazartigues EQadir MMFMauvais-Jarvis F2020Endocrine significance of SARS-CoV-2\u2019s reliance on ACE2. Endocrinology161 bqaa108. (https:\/\/doi.org\/10.1210\/endocr\/bqaa108)"},{"key":"bib64","series-title":"Genes","article-title":"Relative abundance of SARS-CoV-2 entry genes in the enterocytes of the lower gastrointestinal tract","volume":"11","author":"Lee","year":"2020","unstructured":"Lee JJKopetz SVilar EShen JPChen KMaitra A2020Relative abundance of SARS-CoV-2 entry genes in the enterocytes of the lower gastrointestinal tract. Genes11 645. (https:\/\/doi.org\/10.3390\/genes11060645)"},{"key":"bib65","series-title":"Biophysical Journal","doi-asserted-by":"publisher","first-page":"2828","DOI":"10.1016\/j.bpj.2021.05.026","article-title":"Neuropilin-1 assists SARS-CoV-2 infection by stimulating the separation of Spike protein S1 and S2","volume":"120","author":"Li","year":"2021","unstructured":"Li ZLBuck M2021Neuropilin-1 assists SARS-CoV-2 infection by stimulating the separation of Spike protein S1 and S2. Biophysical Journal1202828\u20132837. (https:\/\/doi.org\/10.1016\/j.bpj.2021.05.026)10.1016\/j.bpj.2021.05.026"},{"key":"bib66","series-title":"iScience","article-title":"The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike","volume":"23","author":"Li","year":"2020","unstructured":"Li YZhang ZYang LLian XXie YLi SXin SCao PLu J2020The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike. iScience23 101160. (https:\/\/doi.org\/10.1016\/j.isci.2020.101160)"},{"key":"bib67","series-title":"mBio","article-title":"The TMPRSS2 inhibitor nafamostat reduces SARS-CoV-2 pulmonary infection in mouse models of COVID-19","volume":"12","author":"Li","year":"2021","unstructured":"Li KMeyerholz DKBartlett JAMcCray PBJ2021The TMPRSS2 inhibitor nafamostat reduces SARS-CoV-2 pulmonary infection in mouse models of COVID-19. mBio12 e0097021. (https:\/\/doi.org\/10.1128\/mBio.00970-21)"},{"key":"bib68","series-title":"Clinical Gastroenterology and Hepatology","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1016\/j.cgh.2020.04.040","article-title":"ACE2 expression in pancreas may cause pancreatic damage after SARS-CoV-2 infection","volume":"18","author":"Liu","year":"2020","unstructured":"Liu FLong XZhang BZhang WChen XZhang Z2020ACE2 expression in pancreas may cause pancreatic damage after SARS-CoV-2 infection. Clinical Gastroenterology and Hepatology182128.e2\u20132130.e2. (https:\/\/doi.org\/10.1016\/j.cgh.2020.04.040)10.1016\/j.cgh.2020.04.040"},{"key":"bib69","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1007\/s00125-019-4834-0","article-title":"Cellular proliferation in mouse and human pancreatic islets is regulated by serpin B13 inhibition and downstream targeting of E-cadherin by cathepsin L","volume":"62","author":"Lo","year":"2019","unstructured":"Lo CWKryvalap YSheu TJChang CHCzyzyk J2019Cellular proliferation in mouse and human pancreatic islets is regulated by serpin B13 inhibition and downstream targeting of E-cadherin by cathepsin L. Diabetologia62822\u2013834. (https:\/\/doi.org\/10.1007\/s00125-019-4834-0)10.1007\/s00125-019-4834-0"},{"key":"bib70","series-title":"PNAS","doi-asserted-by":"publisher","first-page":"12319","DOI":"10.1073\/pnas.0800340105","article-title":"Role of furin in granular acidification in the endocrine pancreas: identification of the V-ATPase subunit Ac45 as a candidate substrate","volume":"105","author":"Louagie","year":"2008","unstructured":"Louagie ETaylor NAFlamez DRoebroek AJMBright NAMeulemans SQuintens RHerrera PLSchuit FVan de Ven WJM2008Role of furin in granular acidification in the endocrine pancreas: identification of the V-ATPase subunit Ac45 as a candidate substrate. PNAS10512319\u201312324. (https:\/\/doi.org\/10.1073\/pnas.0800340105)10.1073\/pnas.0800340105"},{"key":"bib71","series-title":"Journal of Clinical Investigation","doi-asserted-by":"publisher","first-page":"2934","DOI":"10.1172\/JCI25485","article-title":"Cathepsin L is essential for onset of autoimmune diabetes in NOD mice","volume":"115","author":"Maehr","year":"2005","unstructured":"Maehr RMintern JDHerman AELennon-Dum\u00e9nil AMMathis DBenoist CPloegh HL2005Cathepsin L is essential for onset of autoimmune diabetes in NOD mice. Journal of Clinical Investigation1152934\u20132943. (https:\/\/doi.org\/10.1172\/JCI25485)10.1172\/JCI25485"},{"key":"bib72","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1007\/s00125-007-0816-8","article-title":"The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients","volume":"50","author":"Marchetti","year":"2007","unstructured":"Marchetti PBugliani MLupi RMarselli LMasini MBoggi UFilipponi FWeir GCEizirik DLCnop M2007The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia502486\u20132494. (https:\/\/doi.org\/10.1007\/s00125-007-0816-8)10.1007\/s00125-007-0816-8"},{"key":"bib73","series-title":"Frontiers in Pharmacology","doi-asserted-by":"publisher","first-page":"584637","DOI":"10.3389\/fphar.2020.584637","article-title":"Age-dependent assessment of genes involved in cellular senescence, telomere, and mitochondrial pathways in human lung tissue of smokers, COPD, and IPF: associations with SARS-CoV-2 COVID-19 ACE2-TMPRSS2-Furin-DPP4 Axis","volume":"11","author":"Maremanda","year":"2020","unstructured":"Maremanda KPSundar IKLi DRahman I2020Age-dependent assessment of genes involved in cellular senescence, telomere, and mitochondrial pathways in human lung tissue of smokers, COPD, and IPF: associations with SARS-CoV-2 COVID-19 ACE2-TMPRSS2-Furin-DPP4 Axis. Frontiers in Pharmacology11584637. (https:\/\/doi.org\/10.3389\/fphar.2020.584637)10.3389\/fphar.2020.584637"},{"key":"bib74","series-title":"Cell Reports","article-title":"Persistent or transient human \u03b2 cell dysfunction induced by metabolic stress: specific signatures and shared gene expression with type 2 diabetes","volume":"33","author":"Marselli","year":"2020","unstructured":"Marselli LPiron ASuleiman MColli MLYi XKhamis ACarrat GRRutter GABugliani MGiusti L2020Persistent or transient human \u03b2 cell dysfunction induced by metabolic stress: specific signatures and shared gene expression with type 2 diabetes. Cell Reports33 108466. (https:\/\/doi.org\/10.1016\/j.celrep.2020.108466)"},{"key":"bib75","series-title":"PNAS","doi-asserted-by":"publisher","first-page":"12543","DOI":"10.1073\/pnas.0503203102","article-title":"Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection","volume":"102","author":"Matsuyama","year":"2005","unstructured":"Matsuyama SUjike MMorikawa STashiro MTaguchi F2005Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. PNAS10212543\u201312547. (https:\/\/doi.org\/10.1073\/pnas.0503203102)10.1073\/pnas.0503203102"},{"key":"bib76","series-title":"Biology","article-title":"SARS-CoV-2 infection and pancreatic beta-cell failure","volume":"11","author":"Mine","year":"2021","unstructured":"Mine KNagafuchi SMori HTakahashi HAnzai K2021SARS-CoV-2 infection and pancreatic beta-cell failure. Biology11 22. (https:\/\/doi.org\/10.3390\/biology11010022)"},{"key":"bib77","series-title":"Lancet: Diabetes and Endocrinology","first-page":"671","article-title":"Temporal trends in emergency admissions for diabetic ketoacidosis in people with diabetes in England before and during the COVID-19 pandemic: a population-based study","volume":"9","author":"Misra","year":"2021","unstructured":"Misra SBarron EVamos EThomas SDhatariya KKar PYoung BKhunti KValabhji J2021Temporal trends in emergency admissions for diabetic ketoacidosis in people with diabetes in England before and during the COVID-19 pandemic: a population-based study. Lancet: Diabetes and Endocrinology9671\u2013680. (https:\/\/doi.org\/10.1016\/S2213-8587(2100208-4)"},{"key":"bib78","series-title":"Nature Metabolism","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1038\/s42255-021-00347-1","article-title":"SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas","volume":"3","author":"M\u00fcller","year":"2021","unstructured":"M\u00fcller JAGro\u00df RConzelmann CKr\u00fcger JMerle USteinhart JWeil TKoepke LBozzo CPRead C2021SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nature Metabolism3149\u2013165. (https:\/\/doi.org\/10.1038\/s42255-021-00347-1)10.1038\/s42255-021-00347-1"},{"key":"bib79","series-title":"PLoS Pathogens","article-title":"SARS-CoV-2 tropism, entry, replication, and propagation: considerations for drug discovery and development","volume":"17","author":"Murgolo","year":"2021","unstructured":"Murgolo NTherien AGHowell BKlein DKoeplinger KLieberman LAAdam GCFlynn JMcKenna PSwaminathan G2021SARS-CoV-2 tropism, entry, replication, and propagation: considerations for drug discovery and development. PLoS Pathogens17 e1009225. (https:\/\/doi.org\/10.1371\/journal.ppat.1009225)"},{"key":"bib80","series-title":"Thrombosis and Haemostasis","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1055\/s-0040-1721319","article-title":"Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the spike S1 receptor-binding domain with heparin","volume":"120","author":"Mycroft-West","year":"2020","unstructured":"Mycroft-West CJSu DPagani IRudd TRElli SGandhi NSGuimond SEMiller GJMeneghetti MCZNader HB2020Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the spike S1 receptor-binding domain with heparin. Thrombosis and Haemostasis1201700\u20131715. (https:\/\/doi.org\/10.1055\/s-0040-1721319)10.1055\/s-0040-1721319"},{"key":"bib81","series-title":"Biochemical Journal","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1042\/BJ20101569","article-title":"Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting","volume":"434","author":"Ni","year":"2011","unstructured":"Ni MZhang YLee AS2011Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting. Biochemical Journal434181\u2013188. (https:\/\/doi.org\/10.1042\/BJ20101569)10.1042\/BJ20101569"},{"key":"bib82","series-title":"Diabetes Care","doi-asserted-by":"publisher","first-page":"e64","DOI":"10.2337\/dc20-1824","article-title":"Association between DPP-4 inhibitors and COVID-19-related outcomes among patients with type 2 diabetes","volume":"44","author":"Noh","year":"2021","unstructured":"Noh YOh ISJeong HEFilion KBYu OHYShin JY2021Association between DPP-4 inhibitors and COVID-19-related outcomes among patients with type 2 diabetes. Diabetes Care44e64\u2013e66. (https:\/\/doi.org\/10.2337\/dc20-1824)10.2337\/dc20-1824"},{"key":"bib83","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1007\/s00125-014-3299-4","article-title":"Dipeptidyl peptidase 4 (DPP-4) is expressed in mouse and human islets and its activity is decreased in human islets from individuals with type 2 diabetes","volume":"57","author":"Omar","year":"2014","unstructured":"Omar BALiehua LYamada YSeino YMarchetti PAhr\u00e9n B2014Dipeptidyl peptidase 4 (DPP-4) is expressed in mouse and human islets and its activity is decreased in human islets from individuals with type 2 diabetes. Diabetologia571876\u20131883. (https:\/\/doi.org\/10.1007\/s00125-014-3299-4)10.1007\/s00125-014-3299-4"},{"key":"bib84","series-title":"Nature Genetics","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1038\/s41588-020-00731-9","article-title":"Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor","volume":"52","author":"Onabajo","year":"2020","unstructured":"Onabajo OOBanday ARStanifer MLYan WObajemu ASanter DMFlorez-Vargas OPiontkivska HVargas JMRing TJ2020Interferons and viruses induce a novel truncated ACE2 isoform and not the full-length SARS-CoV-2 receptor. Nature Genetics521283\u20131293. (https:\/\/doi.org\/10.1038\/s41588-020-00731-9)10.1038\/s41588-020-00731-9"},{"key":"bib85","series-title":"PLoS Computational Biology","article-title":"Targeting TMPRSS2 and cathepsin B\/L together may be synergistic against SARS-CoV-2 infection","volume":"16","author":"Padmanabhan","year":"2020","unstructured":"Padmanabhan PDesikan RDixit NM2020Targeting TMPRSS2 and cathepsin B\/L together may be synergistic against SARS-CoV-2 infection. PLoS Computational Biology16 e1008461. (https:\/\/doi.org\/10.1371\/journal.pcbi.1008461)"},{"key":"bib86","series-title":"International Journal of Molecular Sciences","article-title":"Severe COVID-19 patients show an increase in soluble TNFR1 and ADAM17, with a relationship to mortality","volume":"22","author":"Palacios","year":"2021","unstructured":"Palacios YRuiz ARam\u00f3n-Luing LAOca\u00f1a-Guzman RBarreto-Rodriguez OS\u00e1nchez-Monciv\u00e1is ATecuatzi-Cadena BRegalado-Garc\u00eda AGPineda-Gudi\u00f1o RDGarc\u00eda-Mart\u00ednez A2021Severe COVID-19 patients show an increase in soluble TNFR1 and ADAM17, with a relationship to mortality. International Journal of Molecular Sciences22 8423. (https:\/\/doi.org\/10.3390\/ijms22168423)"},{"key":"bib87","series-title":"PLoS Pathogens","article-title":"Furin cleavage of SARS-CoV-2 spike promotes but is not essential for infection and cell-cell fusion","volume":"17","author":"Papa","year":"2021","unstructured":"Papa GMallery DLAlbecka AWelch LGCattin-Ortol\u00e1 JLuptak JPaul DMcMahon HTGoodfellow IGCarter A2021Furin cleavage of SARS-CoV-2 spike promotes but is not essential for infection and cell-cell fusion. PLoS Pathogens17 e1009246. (https:\/\/doi.org\/10.1371\/journal.ppat.1009246)"},{"key":"bib88","series-title":"Nature Microbiology","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/s41564-021-00908-w","article-title":"The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets","volume":"6","author":"Peacock","year":"2021","unstructured":"Peacock TPGoldhill DHZhou JBaillon LFrise RSwann OCKugathasan RPenn RBrown JCSanchez-David RY2021The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nature Microbiology6899\u2013909. (https:\/\/doi.org\/10.1038\/s41564-021-00908-w)10.1038\/s41564-021-00908-w"},{"key":"bib89","series-title":"Biochemical Journal","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1042\/BJ20071639","article-title":"Neuropilins: structure, function and role in disease","volume":"411","author":"Pellet-Many","year":"2008","unstructured":"Pellet-Many CFrankel PJia HZachary I2008Neuropilins: structure, function and role in disease. Biochemical Journal411211\u2013226. (https:\/\/doi.org\/10.1042\/BJ20071639)10.1042\/BJ20071639"},{"key":"bib90","series-title":"Diabetologia","article-title":"Interferon-\u03b3 potentiates endoplasmic reticulum stress-induced death by reducing pancreatic beta cell defence mechanisms","volume":"49","author":"Pirot","year":"2006","unstructured":"Pirot PEizirik DLCardozo AK2006Interferon-\u03b3 potentiates endoplasmic reticulum stress-induced death by reducing pancreatic beta cell defence mechanisms. Diabetologia49 1229\u20131236. (https:\/\/doi.org\/10.1007\/s00125-006-0214-7)"},{"key":"bib91","series-title":"JCI Insight","article-title":"SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes","volume":"6","author":"Qadir","year":"2021","unstructured":"Qadir MMFBhondeley MBeatty WGaupp DDDoyle-Meyers LAFischer TBandyopadhyay IBlair RVBohm RRappaport J2021SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes. JCI Insight6 e151551. (https:\/\/doi.org\/10.1172\/jci.insight.151551)"},{"key":"bib92","series-title":"EBiomedicine","article-title":"Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: phase 1b\/2a experimental study to investigate safety, pharmacokinetics and pharmacodynamics","volume":"76","author":"Quinn","year":"2022","unstructured":"Quinn TMGaughan EEBruce AAntonelli JO\u2019Connor RLi FMcNamara SKoch OMacKintosh CDockrell D2022Randomised controlled trial of intravenous nafamostat mesylate in COVID pneumonitis: phase 1b\/2a experimental study to investigate safety, pharmacokinetics and pharmacodynamics. EBiomedicine76 103856. (https:\/\/doi.org\/10.1016\/j.ebiom.2022.103856)"},{"key":"bib93","series-title":"mSphere","article-title":"Human basigin (CD147) does not directly interact with SARS-CoV-2 spike glycoprotein","volume":"6","author":"Ragotte","year":"2021","unstructured":"Ragotte RJPulido DDonnellan FRHill MLGorini GDavies HBrun JMcHugh KKing LDWSkinner K2021Human basigin (CD147) does not directly interact with SARS-CoV-2 spike glycoprotein. mSphere6 e0064721. (https:\/\/doi.org\/10.1128\/mSphere.00647-21)"},{"key":"bib94","series-title":"bioRxiv","article-title":"SARS-CoV-2 activat","author":"Rosa-Fernandes","year":"2021","unstructured":"Rosa-Fernandes LLazari LCda Silva JMde Morais Gomes VMachado RRGdos Santos AFAraujo DBCoutinho JVPArini GSAngeli CB2021SARS-CoV-2 activates ER stress and unfolded protein response. bioRxiv [epub]. (https:\/\/doi.org\/10.1101\/2021.06.21.449284)"},{"key":"bib95","series-title":"Oncogene","doi-asserted-by":"publisher","first-page":"3621","DOI":"10.1038\/onc.2011.522","article-title":"The unfolded protein response controls induction and activation of ADAM17\/TACE by severe hypoxia and ER stress","volume":"31","author":"Rzymski","year":"2012","unstructured":"Rzymski TPetry AKra\u010dun DRie\u00df FPike LHarris ALG\u00f6rlach A2012The unfolded protein response controls induction and activation of ADAM17\/TACE by severe hypoxia and ER stress. Oncogene313621\u20133634. (https:\/\/doi.org\/10.1038\/onc.2011.522)10.1038\/onc.2011.522"},{"key":"bib96","series-title":"Life Sciences","article-title":"High GRP78 levels in Covid-19 infection: a case-control study","volume":"265","author":"Sabirli","year":"2021","unstructured":"Sabirli RKoseler AGoren TTurkcuer IKurt O2021High GRP78 levels in Covid-19 infection: a case-control study. Life Sciences265 118781. (https:\/\/doi.org\/10.1016\/j.lfs.2020.118781)"},{"key":"bib97","series-title":"Diabetes Research and Clinical Practice","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition","volume":"157","author":"Saeedi","year":"2019","unstructured":"Saeedi PPetersohn ISalpea PMalanda BKaruranga SUnwin NColagiuri SGuariguata LMotala AAOgurtsova K2019Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Research and Clinical Practice157 107843. (https:\/\/doi.org\/10.1016\/j.diabres.2019.107843)"},{"key":"bib98","series-title":"Endocrine Pathology","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1385\/EP:11:1:31","article-title":"Proprotein-processing endoprotease furin and its substrate parathyroid hormone-related protein are coexpressed in insulinoma cells","volume":"11","author":"Sawada","year":"2000","unstructured":"Sawada YKameya TAizama TIzumi TTakeuchi T2000Proprotein-processing endoprotease furin and its substrate parathyroid hormone-related protein are coexpressed in insulinoma cells. Endocrine Pathology1131\u201339. (https:\/\/doi.org\/10.1385\/EP:11:1:31)10.1385\/EP:11:1:31"},{"key":"bib99","series-title":"FEBS Letters","doi-asserted-by":"publisher","first-page":"3567","DOI":"10.1002\/1873-3468.12858","article-title":"GRP78 protects a disintegrin and metalloprotease 17 against protein-disulfide isomerase A6 catalyzed inactivation","volume":"591","author":"Sch\u00e4fer","year":"2017","unstructured":"Sch\u00e4fer MGranato DCKrossa SBartels AKYokoo SD\u00fcsterh\u00f6ft SKoudelka TScheidig AJTholey APaes Leme AF2017GRP78 protects a disintegrin and metalloprotease 17 against protein-disulfide isomerase A6 catalyzed inactivation. FEBS Letters5913567\u20133587. (https:\/\/doi.org\/10.1002\/1873-3468.12858)10.1002\/1873-3468.12858"},{"key":"bib100","series-title":"American Journal of Therapeutics","first-page":"e358","article-title":"Shedding light on COVID-19: ADAM17 the missing link?","volume":"28","author":"Schreiber","year":"2020","unstructured":"Schreiber BPatel AVerma A2020Shedding light on COVID-19: ADAM17 the missing link?American Journal of Therapeutics28e358\u2013e360. (https:\/\/doi.org\/10.1097\/MJT.0000000000001226)"},{"key":"bib101","series-title":"Cell Metabolism","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.cmet.2016.08.020","article-title":"Single-cell transcriptome profiling of human pancreatic islets in health and type 2 diabetes","volume":"24","author":"Segerstolpe","year":"2016","unstructured":"Segerstolpe \u00c5Palasantza AEliasson PAndersson EMAndr\u00e9asson ACSun XPicelli SSabirsh AClausen MBjursell MK2016Single-cell transcriptome profiling of human pancreatic islets in health and type 2 diabetes. Cell Metabolism24593\u2013607. (https:\/\/doi.org\/10.1016\/j.cmet.2016.08.020)10.1016\/j.cmet.2016.08.020"},{"key":"bib102","series-title":"PNAS","doi-asserted-by":"publisher","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell entry mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","unstructured":"Shang JWan YLuo CYe GGeng QAuerbach ALi F2020Cell entry mechanisms of SARS-CoV-2. PNAS11711727\u201311734. (https:\/\/doi.org\/10.1073\/pnas.2003138117)10.1073\/pnas.2003138117"},{"key":"bib103","series-title":"Journal of Histochemistry and Cytochemistry","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1177\/002215549704500102","article-title":"Localization of endogenous furin in cultured cell lines","volume":"45","author":"Shapiro","year":"1997","unstructured":"Shapiro JSciaky NLee JBosshart HAngeletti RHBonifacino JS1997Localization of endogenous furin in cultured cell lines. Journal of Histochemistry and Cytochemistry453\u201312. (https:\/\/doi.org\/10.1177\/002215549704500102)10.1177\/002215549704500102"},{"key":"bib104","series-title":"Scientific Reports","article-title":"No evidence for basigin\/CD147 as a direct SARS-CoV-2 spike binding receptor","volume":"11","author":"Shilts","year":"2021","unstructured":"Shilts JCrozier TWMGreenwood EJDLehner PJWright GJ2021No evidence for basigin\/CD147 as a direct SARS-CoV-2 spike binding receptor. Scientific Reports11 413. (https:\/\/doi.org\/10.1038\/s41598-020-80464-1)"},{"key":"bib105","series-title":"Nature Communications","article-title":"Viral infiltration of pancreatic islets in patients with COVID-19","volume":"12","author":"Steenblock","year":"2021","unstructured":"Steenblock CRichter SBerger IBarovic MSchmid JSchubert UJarzebska Nvon M\u00e4ssenhausen ALinkermann ASch\u00fcrmann A2021Viral infiltration of pancreatic islets in patients with COVID-19. Nature Communications12 3534. (https:\/\/doi.org\/10.1038\/s41467-021-23886-3)"},{"key":"bib106","series-title":"Biochemical and Biophysical Research Communications","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.bbrc.2009.03.140","article-title":"Important role of heparan sulfate in postnatal islet growth and insulin secretion","volume":"383","author":"Takahashi","year":"2009","unstructured":"Takahashi INoguchi NNata KYamada SKaneiwa TMizumoto SIkeda TSugihara KAsano MYoshikawa T2009Important role of heparan sulfate in postnatal islet growth and insulin secretion. Biochemical and Biophysical Research Communications383113\u2013118. (https:\/\/doi.org\/10.1016\/j.bbrc.2009.03.140)10.1016\/j.bbrc.2009.03.140"},{"key":"bib107","series-title":"Biology","article-title":"Expression profile of SARS-CoV-2 host receptors in human pancreatic islets revealed upregulation of ACE2 in diabetic donors","volume":"9","author":"Taneera","year":"2020","unstructured":"Taneera JEl-Huneidi WHamad MMohammed AKElaraby EHachim MY2020Expression profile of SARS-CoV-2 host receptors in human pancreatic islets revealed upregulation of ACE2 in diabetic donors. Biology9 215. (https:\/\/doi.org\/10.3390\/biology9080215)"},{"key":"bib108","series-title":"Cell Death and Differentiation","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1038\/cdd.2012.60","article-title":"CD147 induces UPR to inhibit apoptosis and chemosensitivity by increasing the transcription of Bip in hepatocellular carcinoma","volume":"19","author":"Tang","year":"2012","unstructured":"Tang JGuo YSZhang YYu XLLi LHuang WLi YChen BJiang JLChen ZN2012CD147 induces UPR to inhibit apoptosis and chemosensitivity by increasing the transcription of Bip in hepatocellular carcinoma. Cell Death and Differentiation191779\u20131790. (https:\/\/doi.org\/10.1038\/cdd.2012.60)10.1038\/cdd.2012.60"},{"key":"bib109","series-title":"bioRxiv","article-title":"Transferrin receptor is another receptor for SARS-CoV","author":"Tang","year":"2020","unstructured":"Tang XYang MDuan ZLiao ZLiu LCheng RFang MWang GLiu HXu J2020Transferrin receptor is another receptor for SARS-CoV-2 entry. bioRxiv [epub]. (https:\/\/doi.org\/10.1101\/2020.10.23.350348)"},{"key":"bib110","series-title":"Cell Metabolism","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/j.cmet.2021.05.015","article-title":"SARS-CoV-2 infection induces beta cell transdifferentiation","volume":"33","author":"Tang","year":"2021a","unstructured":"Tang XUhl SZhang TXue DLi BVandana JJAcklin JABonnycastle LLNarisu NErdos MR2021aSARS-CoV-2 infection induces beta cell transdifferentiation. Cell Metabolism331577.e7\u20131591.e7. (https:\/\/doi.org\/10.1016\/j.cmet.2021.05.015)10.1016\/j.cmet.2021.05.015"},{"key":"bib111","series-title":"ACS Infectious Diseases","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1021\/acsinfecdis.0c00701","article-title":"Proteolytic activation of SARS-CoV-2 spike at the S1\/S2 boundary: potential role of proteases beyond furin","volume":"7","author":"Tang","year":"2021b","unstructured":"Tang TJaimes JABidon MKStraus MRDaniel SWhittaker GR2021bProteolytic activation of SARS-CoV-2 spike at the S1\/S2 boundary: potential role of proteases beyond furin. ACS Infectious Diseases7264\u2013272. (https:\/\/doi.org\/10.1021\/acsinfecdis.0c00701)10.1021\/acsinfecdis.0c00701"},{"key":"bib112","series-title":"Nature","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41586-021-03792-w","article-title":"After the pandemic: perspectives on the future trajectory of COVID-19","volume":"596","author":"Telenti","year":"2021","unstructured":"Telenti AArvin ACorey LCorti DDiamond MSGarc\u00eda-Sastre AGarry RFHolmes ECPang PSVirgin HW2021After the pandemic: perspectives on the future trajectory of COVID-19. Nature596495\u2013504. (https:\/\/doi.org\/10.1038\/s41586-021-03792-w)10.1038\/s41586-021-03792-w"},{"key":"bib113","series-title":"Nature Reviews: Molecular Cell Biology","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/nrm934","article-title":"Furin at the cutting edge: from protein traffic to embryogenesis and disease","volume":"3","author":"Thomas","year":"2002","unstructured":"Thomas G2002Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nature Reviews: Molecular Cell Biology3753\u2013766. (https:\/\/doi.org\/10.1038\/nrm934)10.1038\/nrm934"},{"key":"bib114","series-title":"Science","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","unstructured":"Uhl\u00e9n MFagerberg LHallstr\u00f6m BMLindskog COksvold PMardinoglu ASivertsson \u00c5Kampf CSj\u00f6stedt EAsplund A2015Proteomics. Tissue-based map of the human proteome. Science347 1260419. (https:\/\/doi.org\/10.1126\/science.1260419)"},{"key":"bib115","series-title":"Stem Cell Reviews and Reports","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1007\/s12015-020-09976-7","article-title":"CD147 as a target for COVID-19 treatment: suggested effects of azithromycin and stem cell engagement","volume":"16","author":"Ulrich","year":"2020","unstructured":"Ulrich HPillat MM2020CD147 as a target for COVID-19 treatment: suggested effects of azithromycin and stem cell engagement. Stem Cell Reviews and Reports16434\u2013440. (https:\/\/doi.org\/10.1007\/s12015-020-09976-7)10.1007\/s12015-020-09976-7"},{"key":"bib116","series-title":"ERJ Open Research","first-page":"00848","article-title":"Increased blood angiotensin converting enzyme 2 activity in critically ill COVID-19 patients","volume":"7","author":"van Lier","year":"2021","unstructured":"van Lier DKox MSantos Kvan der Hoeven HPillay JPickkers P2021Increased blood angiotensin converting enzyme 2 activity in critically ill COVID-19 patients. ERJ Open Research700848\u201302020. (https:\/\/doi.org\/10.1183\/23120541.00848-2020)"},{"key":"bib117","series-title":"Emerging Microbes and Infections","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1080\/22221751.2020.1739565","article-title":"Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26","volume":"9","author":"Vankadari","year":"2020","unstructured":"Vankadari NWilce JA2020Emerging COVID-19 coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerging Microbes and Infections9601\u2013604. (https:\/\/doi.org\/10.1080\/22221751.2020.1739565)10.1080\/22221751.2020.1739565"},{"key":"bib118","series-title":"Endocrine Practice","doi-asserted-by":"publisher","first-page":"971","DOI":"10.4158\/EP161679.RA","article-title":"Diabetic ketoacidosis: a common debut of diabetes among African Americans with type 2 diabetes","volume":"23","author":"Vellanki","year":"2017","unstructured":"Vellanki PUmpierrez GE2017Diabetic ketoacidosis: a common debut of diabetes among African Americans with type 2 diabetes. Endocrine Practice23971\u2013978. (https:\/\/doi.org\/10.4158\/EP161679.RA)10.4158\/EP161679.RA"},{"key":"bib119","series-title":"BMJ Open Diabetes Research and Care","article-title":"Risk factors for adverse outcomes among 35 879 veterans with and without diabetes after diagnosis with COVID-19","volume":"9","author":"Wander","year":"2021","unstructured":"Wander PLLowy EBeste LATulloch-Palomino LKorpak APeterson ACYoung BABoyko EJ2021Risk factors for adverse outcomes among 35 879 veterans with and without diabetes after diagnosis with COVID-19. BMJ Open Diabetes Research and Care9 e002252. (https:\/\/doi.org\/10.1136\/bmjdrc-2021-002252)"},{"key":"bib120","series-title":"Diabetes Care","doi-asserted-by":"publisher","first-page":"782","DOI":"10.2337\/dc21-1686","article-title":"The incidence of diabetes among 2,777,768 veterans with and without recent SARS-CoV-2 infection","volume":"45","author":"Wander","year":"2022","unstructured":"Wander PLLowy EBeste LATulloch-Palomino LKorpak APeterson ACKahn SEBoyko EJ2022The incidence of diabetes among 2,777,768 veterans with and without recent SARS-CoV-2 infection. Diabetes Care45782\u2013788. (https:\/\/doi.org\/10.2337\/dc21-1686)10.2337\/dc21-1686"},{"key":"bib121","series-title":"Cell Stress and Chaperones","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s12192-008-0053-1","article-title":"The altered expression of glucose-regulated proteins 78 in different phase of streptozotocin-affected pancreatic beta-cells","volume":"14","author":"Wang","year":"2009","unstructured":"Wang MWang PPeng JLWu SZhao XPLi LShen GX2009The altered expression of glucose-regulated proteins 78 in different phase of streptozotocin-affected pancreatic beta-cells. Cell Stress and Chaperones1443\u201348. (https:\/\/doi.org\/10.1007\/s12192-008-0053-1)10.1007\/s12192-008-0053-1"},{"key":"bib122","series-title":"Signal Transduction and Targeted Therapy","article-title":"CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells","volume":"5","author":"Wang","year":"2020","unstructured":"Wang KChen WZhang ZDeng YLian JQDu PWei DZhang YSun XXGong L2020CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells. Signal Transduction and Targeted Therapy5 283. (https:\/\/doi.org\/10.1038\/s41392-020-00426-x)"},{"key":"bib123","series-title":"Nature Metabolism","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1038\/s42255-020-00324-0","article-title":"HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry","volume":"2","author":"Wei","year":"2020","unstructured":"Wei CWan LYan QWang XZhang JYang XZhang YFan CLi DDeng Y2020HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry. Nature Metabolism21391\u20131400. (https:\/\/doi.org\/10.1038\/s42255-020-00324-0)10.1038\/s42255-020-00324-0"},{"key":"bib124","series-title":"Scientific Reports","article-title":"SARS-CoV-2 receptor ACE2 is co-expressed with genes related to transmembrane serine proteases, viral entry, immunity and cellular stress","volume":"10","author":"Wruck","year":"2020","unstructured":"Wruck WAdjaye J2020SARS-CoV-2 receptor ACE2 is co-expressed with genes related to transmembrane serine proteases, viral entry, immunity and cellular stress. Scientific Reports10 21415. (https:\/\/doi.org\/10.1038\/s41598-020-78402-2)"},{"key":"bib125","series-title":"Cell Metabolism","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1016\/j.cmet.2021.05.013","article-title":"SARS-CoV-2 infects human pancreatic \u03b2 cells and elicits \u03b2 cell impairment","volume":"33","author":"Wu","year":"2021","unstructured":"Wu CTLidsky PVXiao YLee ITCheng RNakayama TJiang SDemeter JBevacqua RJChang CA2021SARS-CoV-2 infects human pancreatic \u03b2 cells and elicits \u03b2 cell impairment. Cell Metabolism331565.e5\u20131576.e5. (https:\/\/doi.org\/10.1016\/j.cmet.2021.05.013)10.1016\/j.cmet.2021.05.013"},{"key":"bib126","series-title":"Molecules","article-title":"A novel purification procedure for active recombinant human DPP4 and the inability of DPP4 to bind SARS-CoV-2","volume":"25","author":"Xi","year":"2020","unstructured":"Xi CRDi Fazio ANadvi NAPatel KXiang MSWZhang HEDeshpande CLow JKKWang XTChen Y2020A novel purification procedure for active recombinant human DPP4 and the inability of DPP4 to bind SARS-CoV-2. Molecules25 5392. (https:\/\/doi.org\/10.3390\/molecules25225392)"},{"key":"bib127","series-title":"Lancet Diabetes and Endocrinology","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/S2213-8587(22)00044-4","article-title":"Risks and burdens of incident diabetes in long COVID: a cohort study","volume":"10","author":"Xie","year":"2022","unstructured":"Xie YAl-Aly Z2022Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes and Endocrinology10311\u2013321. (https:\/\/doi.org\/10.1016\/S2213-8587(2200044-4)10.1016\/S2213-8587(22)00044-4"},{"key":"bib128","series-title":"Cells","article-title":"The ins and outs of cathepsins: physiological function and role in disease management","volume":"9","author":"Yadati","year":"2020","unstructured":"Yadati THouben TBitorina AShiri-Sverdlov R2020The ins and outs of cathepsins: physiological function and role in disease management. Cells9 1679. (https:\/\/doi.org\/10.3390\/cells9071679)"},{"key":"bib129","series-title":"Acta Diabetologica","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s00592-009-0109-4","article-title":"Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes","volume":"47","author":"Yang","year":"2010","unstructured":"Yang JKLin SSJi XJGuo LM2010Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetologica47193\u2013199. (https:\/\/doi.org\/10.1007\/s00592-009-0109-4)10.1007\/s00592-009-0109-4"},{"key":"bib130","series-title":"Cell Stem Cell","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.stem.2020.06.015","article-title":"A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids","volume":"27","author":"Yang","year":"2020","unstructured":"Yang LHan YNilsson-Payant BEGupta VWang PDuan XTang XZhu JZhao ZJaffr\u00e9 F2020A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids. Cell Stem Cell27125.e7\u2013136.e7. (https:\/\/doi.org\/10.1016\/j.stem.2020.06.015)10.1016\/j.stem.2020.06.015"},{"key":"bib131","series-title":"PLoS ONE","article-title":"DPP-4 inhibitors may improve the mortality of coronavirus disease 2019: a meta-analysis","volume":"16","author":"Yang","year":"2021","unstructured":"Yang YCai ZZhang J2021DPP-4 inhibitors may improve the mortality of coronavirus disease 2019: a meta-analysis. PLoS ONE16 e0251916. (https:\/\/doi.org\/10.1371\/journal.pone.0251916)"},{"key":"bib132","series-title":"Cell","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/j.cell.2021.02.053","article-title":"Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system","volume":"184","author":"Yeung","year":"2021","unstructured":"Yeung MLTeng JLLJia LZhang CHuang CCai JPZhou RChan KHZhao HZhu L2021Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system. Cell1842212.e12\u20132228.e12. (https:\/\/doi.org\/10.1016\/j.cell.2021.02.053)10.1016\/j.cell.2021.02.053"},{"key":"bib133","series-title":"Science Immunology","article-title":"TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes","volume":"5","author":"Zang","year":"2020","unstructured":"Zang RCastro MFGMcCune BTZeng QRothlauf PWSonnek NMLiu ZBrulois KFWang XGreenberg HB2020TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Science Immunology5 eabc3582. (https:\/\/doi.org\/10.1126\/sciimmunol.abc3582)"},{"key":"bib134","series-title":"Cell Discovery","article-title":"Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro","volume":"6","author":"Zhang","year":"2020","unstructured":"Zhang QChen CZSwaroop MXu MWang LLee JWang AQPradhan MHagen NChen L2020Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro. Cell Discovery6 80. (https:\/\/doi.org\/10.1038\/s41421-020-00222-5)"},{"key":"bib135","series-title":"Diabetes","doi-asserted-by":"publisher","first-page":"361","DOI":"10.2337\/diabetes.50.2.361","article-title":"Expression and distribution of lactate\/monocarboxylate transporter isoforms in pancreatic islets and the exocrine pancreas","volume":"50","author":"Zhao","year":"2001","unstructured":"Zhao CWilson MCSchuit FHalestrap APRutter GA2001Expression and distribution of lactate\/monocarboxylate transporter isoforms in pancreatic islets and the exocrine pancreas. Diabetes50361\u2013366. (https:\/\/doi.org\/10.2337\/diabetes.50.2.361)10.2337\/diabetes.50.2.361"},{"key":"bib136","series-title":"Signal Transduction and Targeted Therapy","article-title":"Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development","volume":"6","author":"Zhao","year":"2021","unstructured":"Zhao MMYang WLYang FYZhang LHuang WJHou WFan CFJin RHFeng YMWang YC2021Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development. Signal Transduction and Targeted Therapy6 134. (https:\/\/doi.org\/10.1038\/s41392-021-00558-8)"},{"key":"bib137","series-title":"Nature Communications","article-title":"A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry","volume":"12","author":"Zhu","year":"2021","unstructured":"Zhu YFeng FHu GWang YYu YZhu YXu WCai XSun ZHan W2021A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry. Nature Communications12 961. (https:\/\/doi.org\/10.1038\/s41467-021-21213-4)"},{"key":"bib138","series-title":"EClinicalmedicine","article-title":"Nafamostat in hospitalized patients with moderate to severe COVID-19 pneumonia: a randomised phase II clinical trial","volume":"41","author":"Zhuravel","year":"2021","unstructured":"Zhuravel SVKhmelnitskiy OKBurlaka OOGritsan AIGoloshchekin BMKim SHong KY2021Nafamostat in hospitalized patients with moderate to severe COVID-19 pneumonia: a randomised phase II clinical trial. EClinicalmedicine41 101169. (https:\/\/doi.org\/10.1016\/j.eclinm.2021.101169)"},{"key":"bib139","series-title":"Journal of Clinical Investigation","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1172\/JCI46177","article-title":"Heparan sulfate and heparanase play key roles in mouse \u03b2 cell survival and autoimmune diabetes","volume":"122","author":"Ziolkowski","year":"2012","unstructured":"Ziolkowski AFPopp SKFreeman CParish CRSimeonovic CJ2012Heparan sulfate and heparanase play key roles in mouse \u03b2 cell survival and autoimmune diabetes. Journal of Clinical Investigation122132\u2013141. (https:\/\/doi.org\/10.1172\/JCI46177)10.1172\/JCI46177"},{"key":"bib140","series-title":"Frontiers in Immunology","doi-asserted-by":"publisher","first-page":"576745","DOI":"10.3389\/fimmu.2020.576745","article-title":"ACE2\/ADAM17\/TMPRSS2 interplay may be the main risk factor for COVID-19","volume":"11","author":"Zipeto","year":"2020","unstructured":"Zipeto DPalmeira JDFArga\u00f1araz GAArga\u00f1araz ER2020ACE2\/ADAM17\/TMPRSS2 interplay may be the main risk factor for COVID-19. Frontiers in Immunology11576745. (https:\/\/doi.org\/10.3389\/fimmu.2020.576745).10.3389\/fimmu.2020.576745"}],"container-title":["Journal of Molecular Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/jme.bioscientifica.com\/view\/journals\/jme\/69\/2\/JME-21-0282.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jme.bioscientifica.com\/downloadpdf\/journals\/jme\/69\/2\/JME-21-0282.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jme.bioscientifica.com\/downloadpdf\/journals\/jme\/69\/2\/JME-21-0282.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:10Z","timestamp":1784555650000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/jme\/article\/69\/2\/R63-R79\/14515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,1]]},"references-count":140,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/jme-21-0282","relation":{},"ISSN":["0952-5041","1479-6813"],"issn-type":[{"value":"0952-5041","type":"print"},{"value":"1479-6813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,1]]}}}