{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:09:41Z","timestamp":1768522181233,"version":"3.49.0"},"reference-count":118,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["bmn.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Discovery Today"],"published-print":{"date-parts":[[2024,7]]},"DOI":"10.1016\/j.drudis.2024.104026","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T10:30:14Z","timestamp":1715941814000},"page":"104026","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"title":["Targeting furin, a cellular proprotein convertase, for COVID-19 prevention and therapeutics"],"prefix":"10.1016","volume":"29","author":[{"given":"Xia","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dabing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mazaher","family":"Maghsoudloo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhe","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-2200","authenticated-orcid":false,"given":"Junjiang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.drudis.2024.104026_b0005","unstructured":"WHO. Coronavirus disease (COVID-19) pandemic. World Health Organization. Accessed August 30, 2023. https:\/\/www.who.int\/europe\/emergencies\/situations\/covid-19."},{"key":"10.1016\/j.drudis.2024.104026_b0010","unstructured":"WHO. COVID-19 epidemiological update \u2013 15 March 2024. World Healthy Organization. Accessed March 15, 2024. https:\/\/www.who.int\/publications\/m\/item\/covid-19-epidemiological-update-15-march-2024."},{"key":"10.1016\/j.drudis.2024.104026_b0015","doi-asserted-by":"crossref","first-page":"e0121322","DOI":"10.1128\/spectrum.01213-22","article-title":"SARS-CoV-2 omicron spike simulations: broad antibody escape, weakened ACE2 binding, and modest furin cleavage","volume":"11","author":"Jawaid","year":"2023","journal-title":"Microbiol Spectr"},{"key":"10.1016\/j.drudis.2024.104026_b0020","first-page":"100250","article-title":"Never ending story? Evolution of SARS-CoV-2 monitored through Gibbs energies of biosynthesis and antigen-receptor binding of Omicron BQ.1, BQ.1.1, XBB and XBB.1 variants. Microb","volume":"23","author":"Popovic","year":"2023","journal-title":"Risk Anal"},{"key":"10.1016\/j.drudis.2024.104026_b0025","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s11427-020-1637-5","article-title":"Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission","volume":"63","author":"Xu","year":"2020","journal-title":"Sci China Life Sci"},{"key":"10.1016\/j.drudis.2024.104026_b0030","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.drudis.2024.104026_b0035","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jinf.2020.11.016","article-title":"Outcome prediction by serum calprotectin in patients with COVID-19 in the emergency department","volume":"82","author":"Bauer","year":"2021","journal-title":"J Infect"},{"key":"10.1016\/j.drudis.2024.104026_b0040","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41392-021-00653-w","article-title":"Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy","volume":"6","author":"Zhang","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"10.1016\/j.drudis.2024.104026_b0045","doi-asserted-by":"crossref","first-page":"e9725","DOI":"10.7717\/peerj.9725","article-title":"A comparison of COVID-19, SARS and MERS","volume":"8","author":"Hu","year":"2020","journal-title":"Peerj"},{"key":"10.1016\/j.drudis.2024.104026_b0050","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/0092-8674(84)90442-2","article-title":"Isolation of the putative structural gene for the lysine-arginine-cleaving endopeptidase required for processing of yeast prepro-alpha-factor","volume":"37","author":"Julius","year":"1984","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2024.104026_b0055","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF00364823","article-title":"Characterization of human c-fes\/fps reveals a new transcription unit (fur) in the immediately upstream region of the proto-oncogene","volume":"11","author":"Roebroek","year":"1986","journal-title":"Mol Biol Rep"},{"key":"10.1016\/j.drudis.2024.104026_b0060","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1126\/science.2683070","article-title":"Intracellular targeting and structural conservation of a prohormone-processing endoprotease","volume":"246","author":"Fuller","year":"1989","journal-title":"Science"},{"key":"10.1016\/j.drudis.2024.104026_b0065","doi-asserted-by":"crossref","first-page":"609","DOI":"10.18097\/PBMC20166206609","article-title":"Furin as proprotein convertase and its role in normal and pathological biological processes","volume":"62","author":"Solovyeva","year":"2016","journal-title":"Biomed Khim"},{"key":"10.1016\/j.drudis.2024.104026_b0070","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3390\/v11090837","article-title":"The proteolytic regulation of virus cell entry by furin and other proprotein convertases","volume":"11","author":"Izaguirre","year":"2019","journal-title":"Viruses"},{"key":"10.1016\/j.drudis.2024.104026_b0075","doi-asserted-by":"crossref","first-page":"5762","DOI":"10.1073\/pnas.95.10.5762","article-title":"Processing of the Ebola virus glycoprotein by the proprotein convertase furin","volume":"95","author":"Volchkov","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2024.104026_b0080","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41421-022-00419-w","article-title":"Novel cleavage sites identified in SARS-CoV-2 spike protein reveal mechanism for cathepsin L-facilitated viral infection and treatment strategies","volume":"8","author":"Zhao","year":"2022","journal-title":"Cell Discov"},{"key":"10.1016\/j.drudis.2024.104026_b0085","doi-asserted-by":"crossref","DOI":"10.1177\/11779322211054684","article-title":"Prediction of the effects of variants and differential expression of key host genes ACE2, TMPRSS2, and FURIN in SARS-CoV-2 pathogenesis: an in silico approach","volume":"15","author":"Hossain","year":"2021","journal-title":"Bioinform Biol Insights"},{"key":"10.1016\/j.drudis.2024.104026_b0090","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41586-021-03237-4","article-title":"Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis","volume":"591","author":"Johnson","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2024.104026_b0095","doi-asserted-by":"crossref","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","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.drudis.2024.104026_b0100","doi-asserted-by":"crossref","first-page":"5","DOI":"10.15407\/ubj88.06.005","article-title":"Chemical structure and properties of low-molecular furin inhibitors","volume":"88","author":"Osadchuk","year":"2016","journal-title":"Ukr Biochem J"},{"key":"10.1016\/j.drudis.2024.104026_b0105","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1042\/bj3260737","article-title":"The integrity of the RRGDL sequence of the proprotein convertase PC1 is critical for its zymogen and C-terminal processing and for its cellular trafficking","volume":"326","author":"Lusson","year":"1997","journal-title":"Biochem J"},{"key":"10.1016\/j.drudis.2024.104026_b0110","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.jmb.2004.10.050","article-title":"Proprotein convertase models based on the crystal structures of furin and kexin: explanation of their specificity","volume":"345","author":"Henrich","year":"2005","journal-title":"J Mol Biol"},{"key":"10.1016\/j.drudis.2024.104026_b0115","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbrc.2013.03.073","article-title":"Proteolytic cleavage of LEDA-1\/PIANP by furin-like proprotein convertases precedes its plasma membrane localization","volume":"434","author":"Evdokimov","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.drudis.2024.104026_b0120","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/j.1460-2075.1994.tb06231.x","article-title":"Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface","volume":"13","author":"Molloy","year":"1994","journal-title":"EMBO J"},{"key":"10.1016\/j.drudis.2024.104026_b0125","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/jcp.22792","article-title":"Hypoxia enhances cancer cell invasion through relocalization of the proprotein convertase furin from the trans-Golgi network to the cell surface","volume":"227","author":"Arsenault","year":"2012","journal-title":"J Cell Physiol"},{"key":"10.1016\/j.drudis.2024.104026_b0130","doi-asserted-by":"crossref","first-page":"6561","DOI":"10.1074\/jbc.M413248200","article-title":"Hypoxia-enhanced expression of the proprotein convertase furin is mediated by hypoxia-inducible factor-1: impact on the bioactivation of proproteins","volume":"280","author":"McMahon","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0135","doi-asserted-by":"crossref","first-page":"16108","DOI":"10.1074\/jbc.M600760200","article-title":"Identification of a pH sensor in the furin propeptide that regulates enzyme activation","volume":"281","author":"Feliciangeli","year":"2006","journal-title":"J Biol Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0140","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.3390\/ijms23073435","article-title":"The path to therapeutic furin inhibitors: from yeast pheromones to SARS-CoV-2","volume":"23","author":"Thomas","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.drudis.2024.104026_b0145","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.7150\/ijbs.63072","article-title":"COVID-19 disease and malignant cancers: the impact for the furin gene expression in susceptibility to SARS-CoV-2","volume":"17","author":"Li","year":"2021","journal-title":"Int J Biol Sci"},{"key":"10.1016\/j.drudis.2024.104026_b0150","doi-asserted-by":"crossref","first-page":"5","DOI":"10.15407\/ubj88.06.005","article-title":"Chemical structure and properties of low-molecular furin inhibitors","volume":"88","author":"Osadchuk","year":"2016","journal-title":"Ukr Biochem J"},{"key":"10.1016\/j.drudis.2024.104026_b0155","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1074\/jbc.270.6.2695","article-title":"Endoproteolytic cleavage of its propeptide is a prerequisite for efficient transport of furin out of the endoplasmic reticulum","volume":"270","author":"Creemers","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0160","doi-asserted-by":"crossref","first-page":"e1073","DOI":"10.1002\/cti2.1073","article-title":"Furin-mediated protein processing in infectious diseases and cancer","volume":"8","author":"Braun","year":"2019","journal-title":"Clin Transl Immunology"},{"key":"10.1016\/j.drudis.2024.104026_b0165","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.tibs.2003.12.006","article-title":"The kindest cuts of all: crystal structures of Kex2 and furin reveal secrets of precursor processing","volume":"29","author":"Rockwell","year":"2004","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.drudis.2024.104026_b0170","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/nsb941","article-title":"The crystal structure of the proprotein processing proteinase furin explains its stringent specificity","volume":"10","author":"Henrich","year":"2003","journal-title":"Nat Struct Biol"},{"key":"10.1016\/j.drudis.2024.104026_b0175","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/bj3270625","article-title":"Furin: a mammalian subtilisin\/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins","volume":"327","author":"Nakayama","year":"1997","journal-title":"Biochem J"},{"key":"10.1016\/j.drudis.2024.104026_b0180","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/j.1432-1033.1994.tb18864.x","article-title":"Homology modelling of the catalytic domain of human furin. A model for the eukaryotic subtilisin-like proprotein convertases","volume":"222","author":"Siezen","year":"1994","journal-title":"Eur J Biochem"},{"key":"10.1016\/j.drudis.2024.104026_b0185","doi-asserted-by":"crossref","first-page":"e1073","DOI":"10.1002\/cti2.1073","article-title":"Furin-mediated protein processing in infectious diseases and cancer","volume":"8","author":"Braun","year":"2019","journal-title":"Clin Transl Immunology"},{"key":"10.1016\/j.drudis.2024.104026_b0190","first-page":"197","article-title":"Proprotein convertase furin enhances survival and migration of vascular smooth muscle cells via processing of pro-nerve growth factor","volume":"2","author":"Daniel","year":"2013","journal-title":"J Biochem"},{"key":"10.1016\/j.drudis.2024.104026_b0195","doi-asserted-by":"crossref","first-page":"7061","DOI":"10.1021\/bi034156y","article-title":"Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1","volume":"42","author":"Vardar","year":"2003","journal-title":"Biochemistry"},{"key":"10.1016\/j.drudis.2024.104026_b0200","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.jmb.2011.04.042","article-title":"HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation","volume":"410","author":"Checkley","year":"2011","journal-title":"J Mol Biol"},{"key":"10.1016\/j.drudis.2024.104026_b0205","doi-asserted-by":"crossref","DOI":"10.1016\/j.bpc.2020.106420","article-title":"Delving deep into the structural aspects of a furin cleavage site inserted into the spike protein of SARS-CoV-2: a structural biophysical perspective","volume":"264","author":"Li","year":"2020","journal-title":"Biophys Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0210","article-title":"SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage","author":"Escalera","year":"2021","journal-title":"bioRxiv"},{"key":"10.1016\/j.drudis.2024.104026_b0215","doi-asserted-by":"crossref","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":"2021","journal-title":"ACS Infect Dis"},{"key":"10.1016\/j.drudis.2024.104026_b0220","doi-asserted-by":"crossref","first-page":"7218","DOI":"10.1073\/pnas.131076098","article-title":"Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia","volume":"98","author":"Chen","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2024.104026_b0225","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature02145","article-title":"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus","volume":"426","author":"Li","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2024.104026_b0230","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2024.104026_b0235","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2024.104026_b0240","doi-asserted-by":"crossref","first-page":"16396","DOI":"10.1016\/S0021-9258(18)42016-9","article-title":"Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen","volume":"267","author":"Molloy","year":"1992","journal-title":"J Biol Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0245","doi-asserted-by":"crossref","DOI":"10.3389\/fddsv.2022.899239","article-title":"Furin and COVID-19: structure, function and chemoinformatic analysis of representative active site inhibitors","volume":"2","author":"Villoutreix","year":"2022","journal-title":"Front Drug Discov"},{"key":"10.1016\/j.drudis.2024.104026_b0250","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0092-8674(01)00303-8","article-title":"The fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH","volume":"105","author":"Lescar","year":"2001","journal-title":"Cell"},{"key":"10.1016\/j.drudis.2024.104026_b0255","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev-virology-110615-042301","article-title":"Structure, function, and evolution of coronavirus spike proteins","volume":"3","author":"Li","year":"2016","journal-title":"Annu Rev Virol"},{"key":"10.1016\/j.drudis.2024.104026_b0260","doi-asserted-by":"crossref","first-page":"5010","DOI":"10.1111\/febs.15651","article-title":"The structural basis of accelerated host cell entry by SARS-CoV-2\u2020","volume":"288","author":"Seyran","year":"2020","journal-title":"FEBS J"},{"key":"10.1016\/j.drudis.2024.104026_b0265","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/s41423-020-0374-2","article-title":"Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein","volume":"17","author":"Xia","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"10.1016\/j.drudis.2024.104026_b0270","doi-asserted-by":"crossref","first-page":"e570","DOI":"10.1016\/S2666-5247(23)00144-1","article-title":"The SARS-CoV-2 furin cleavage site: natural selection or smoking gun?","volume":"4","author":"Lubinski","year":"2023","journal-title":"Lancet Microbe"},{"key":"10.1016\/j.drudis.2024.104026_b0275","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41579-020-00468-6","article-title":"Coronavirus biology and replication: implications for SARS-CoV-2","volume":"19","author":"V\u2019kovski","year":"2021","journal-title":"Nat Rev Microbiol"},{"key":"10.1016\/j.drudis.2024.104026_b0280","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.virol.2006.02.003","article-title":"Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry","volume":"350","author":"Follis","year":"2006","journal-title":"Virology"},{"key":"10.1016\/j.drudis.2024.104026_b0285","doi-asserted-by":"crossref","first-page":"8887","DOI":"10.1128\/JVI.00415-08","article-title":"Cathepsin L functionally cleaves the severe acute respiratory syndrome coronavirus class I fusion protein upstream of rather than adjacent to the fusion peptide","volume":"82","author":"Bosch","year":"2008","journal-title":"J Virol"},{"key":"10.1016\/j.drudis.2024.104026_b0290","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.3390\/v15071500","article-title":"SARS-CoV-2 spike protein is capable of inducing cell-cell fusions independent from its receptor ACE2 and this activity can be impaired by furin inhibitors or a subset of monoclonal antibodies","volume":"15","author":"Reuter","year":"2023","journal-title":"Viruses"},{"key":"10.1016\/j.drudis.2024.104026_b0295","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell entry mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2024.104026_b0300","doi-asserted-by":"crossref","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","journal-title":"Nat Microbiol"},{"key":"10.1016\/j.drudis.2024.104026_b0305","doi-asserted-by":"crossref","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":"2020","journal-title":"Mol Cell"},{"key":"10.1016\/j.drudis.2024.104026_b0310","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41594-022-00735-5","article-title":"The SARS-CoV-2 spike reversibly samples an open-trimer conformation exposing novel epitopes","volume":"29","author":"Costello","year":"2022","journal-title":"Nat Struct Mol Biol"},{"key":"10.1016\/j.drudis.2024.104026_b0315","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.3390\/ijerph19084586","article-title":"Is the SARS CoV-2 Omicron variant deadlier and more transmissible than Delta variant?","volume":"19","author":"Duong","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"10.1016\/j.drudis.2024.104026_b0320","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.drudis.2024.104026_b0325","article-title":"Mutations, recombination and insertion in the evolution of 2019-nCoV","author":"Wu","year":"2020","journal-title":"bioRxiv"},{"key":"10.1016\/j.drudis.2024.104026_b0330","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108254","article-title":"Furin inhibitors block SARS-CoV-2 spike protein cleavage to suppress virus production and cytopathic effects","volume":"33","author":"Cheng","year":"2020","journal-title":"Cell Rep"},{"key":"10.1016\/j.drudis.2024.104026_b0335","article-title":"TMPRSS2 and furin are both essential for proteolytic activation and spread of SARS-CoV-2 in human airway epithelial cells and provide promising drug targets","author":"Bestle","year":"2020","journal-title":"bioRxiv"},{"key":"10.1016\/j.drudis.2024.104026_b0340","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1517\/13543776.2014.1000303","article-title":"Therapeutic uses of furin and its inhibitors: a patent review","volume":"25","author":"Couture","year":"2015","journal-title":"Expert Opin Ther Pat"},{"key":"10.1016\/j.drudis.2024.104026_b0345","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.615398","article-title":"Alpha-1 antitrypsin for COVID-19 treatment: dual role in antiviral infection and anti-inflammation","volume":"11","author":"Yang","year":"2020","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.drudis.2024.104026_b0350","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.176017","article-title":"Alpha-1 antitrypsin protects against phosgene-induced acute lung injury by activating the ID1-dependent anti-inflammatory response","volume":"957","author":"He","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.drudis.2024.104026_b0355","doi-asserted-by":"crossref","first-page":"24887","DOI":"10.1016\/S0021-9258(19)74548-7","article-title":"Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant","volume":"268","author":"Anderson","year":"1993","journal-title":"J Biol Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0360","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1073\/pnas.95.13.7293","article-title":"Alpha1-antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent","volume":"95","author":"Jean","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2024.104026_b0365","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/protein\/gzs091","article-title":"Engineering of alpha1-antitrypsin variants with improved specificity for the proprotein convertase furin using site-directed random mutagenesis","volume":"26","author":"Hada","year":"2013","journal-title":"Protein Eng Des Sel"},{"key":"10.1016\/j.drudis.2024.104026_b0370","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1073\/pnas.95.13.7293","article-title":"Alpha1-antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent","volume":"95","author":"Jean","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2024.104026_b0375","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1038\/s41467-021-21972-0","article-title":"Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection","volume":"12","author":"Wettstein","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.drudis.2024.104026_b0380","doi-asserted-by":"crossref","first-page":"12522","DOI":"10.3390\/ijms232012522","article-title":"Reactive centre loop mutagenesis of SerpinB3 to target TMPRSS2 and furin: inhibition of SARS-CoV-2 cell entry and replication","volume":"23","author":"Singh","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.drudis.2024.104026_b0385","doi-asserted-by":"crossref","first-page":"36741","DOI":"10.1074\/jbc.M003848200","article-title":"Polyarginines are potent furin inhibitors","volume":"275","author":"Cameron","year":"2000","journal-title":"J Biol Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0390","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/oxfordjournals.jbchem.a124491","article-title":"Studies on an artificial trypsin inhibitor peptide derived from the mung bean trypsin inhibitor: chemical synthesis, refolding, and crystallographic analysis of its complex with trypsin","volume":"116","author":"Li","year":"1994","journal-title":"J Biochem"},{"key":"10.1016\/j.drudis.2024.104026_b0395","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1128\/IAI.72.1.602-605.2004","article-title":"Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo","volume":"72","author":"Sarac","year":"2004","journal-title":"Infect Immun"},{"key":"10.1016\/j.drudis.2024.104026_b0400","doi-asserted-by":"crossref","first-page":"220","DOI":"10.3109\/02713680903487609","article-title":"Nona-D-arginine amide for prophylaxis and treatment of experimental Pseudomonas aeruginosa keratitis","volume":"35","author":"Karicherla","year":"2010","journal-title":"Curr Eye Res"},{"key":"10.1016\/j.drudis.2024.104026_b0405","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1167\/iovs.08-2344","article-title":"Nona-D-arginine therapy for Pseudomonas aeruginosa keratitis","volume":"50","author":"Karicherla","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1016\/j.drudis.2024.104026_b0410","doi-asserted-by":"crossref","first-page":"8205","DOI":"10.1073\/pnas.1032865100","article-title":"Optimization of protease-inhibitor interactions by randomizing adventitious contacts","volume":"100","author":"Komiyama","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2024.104026_b0415","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1399-3011.1995.tb00594.x","article-title":"Peptidyl substrates containing unnatural amino acid at the P\u20191 position are potent inhibitors of prohormone convertases","volume":"46","author":"Basak","year":"1995","journal-title":"Int J Pept Protein Res"},{"key":"10.1016\/j.drudis.2024.104026_b0420","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/360358a0","article-title":"Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160","volume":"360","author":"Hallenberger","year":"1992","journal-title":"Nature"},{"key":"10.1016\/j.drudis.2024.104026_b0425","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.bbrc.2004.11.063","article-title":"Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus","volume":"326","author":"Bergeron","year":"2005","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.drudis.2024.104026_b0430","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3390\/v11111011","article-title":"Decanoyl-Arg-Val-Lys-Arg-chloromethylketone: an antiviral compound that acts against flaviviruses through the inhibition of furin-mediated prM cleavage","volume":"11","author":"Imran","year":"2019","journal-title":"Viruses"},{"key":"10.1016\/j.drudis.2024.104026_b0435","doi-asserted-by":"crossref","first-page":"9659","DOI":"10.1021\/bi034418w","article-title":"Barley serine proteinase inhibitor 2-derived cyclic peptides as potent and selective inhibitors of convertases PC1\/3 and furin","volume":"42","author":"Villemure","year":"2003","journal-title":"Biochemistry"},{"key":"10.1016\/j.drudis.2024.104026_b0440","doi-asserted-by":"crossref","first-page":"e0130417","DOI":"10.1371\/journal.pone.0130417","article-title":"Cationic cell-penetrating peptides are potent furin inhibitors","volume":"10","author":"Ramos-Molina","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.drudis.2024.104026_b0445","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1021\/cb500087x","article-title":"X-ray structures of human furin in complex with competitive inhibitors","volume":"9","author":"Dahms","year":"2014","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.drudis.2024.104026_b0450","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1021\/jm9012455","article-title":"Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics","volume":"53","author":"Becker","year":"2010","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0455","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1021\/acs.jmedchem.1c00518","article-title":"Why all the fury over furin?","volume":"65","author":"Osman","year":"2022","journal-title":"J Med Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0460","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1021\/acsmedchemlett.0c00651","article-title":"The basicity makes the difference: improved canavanine-derived inhibitors of the proprotein convertase furin","volume":"12","author":"Lam van","year":"2021","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.drudis.2024.104026_b0465","doi-asserted-by":"crossref","first-page":"19225","DOI":"10.1074\/jbc.270.33.19225","article-title":"Fluorescent peptidyl substrates as an aid in studying the substrate specificity of human prohormone convertase PC1 and human furin and designing a potent irreversible inhibitor","volume":"270","author":"Jean","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0470","doi-asserted-by":"crossref","first-page":"19707","DOI":"10.1073\/pnas.0606555104","article-title":"Synthetic small molecule furin inhibitors derived from 2,5-dideoxystreptamine","volume":"103","author":"Jiao","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.drudis.2024.104026_b0475","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1021\/acschembio.7b00633","article-title":"Structural studies revealed active site distortions of human furin by a small molecule inhibitor","volume":"12","author":"Dahms","year":"2017","journal-title":"ACS Chem Biol"},{"key":"10.1016\/j.drudis.2024.104026_b0480","doi-asserted-by":"crossref","first-page":"e0012822","DOI":"10.1128\/jvi.00128-22","article-title":"Distinctive roles of furin and TMPRSS2 in SARS-CoV-2 infectivity","volume":"96","author":"Essalmani","year":"2022","journal-title":"J Virol"},{"key":"10.1016\/j.drudis.2024.104026_b0485","doi-asserted-by":"crossref","first-page":"4589","DOI":"10.1016\/j.csbj.2023.09.003","article-title":"W254 in furin functions as a molecular gate promoting anti-viral drug binding: elucidation of putative drug tunneling and docking by non-equilibrium molecular dynamics","volume":"21","author":"Ridgway","year":"2023","journal-title":"Comput Struct Biotechnol J"},{"key":"10.1016\/j.drudis.2024.104026_b0490","series-title":"Regulation of carcinogenesis, angiogenesis and metastasis by the proprotein convertases (PCs): a new potential strategy in cancer therapy","first-page":"137","article-title":"Evaluation of anti-proprotein convertase activity of diterpene andrographolid derived products","author":"Basak","year":"2006"},{"key":"10.1016\/j.drudis.2024.104026_b0495","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.antiviral.2017.03.026","article-title":"Luteolin restricts dengue virus replication through inhibition of the proprotein convertase furin","volume":"143","author":"Peng","year":"2017","journal-title":"Antiviral Res"},{"key":"10.1016\/j.drudis.2024.104026_b0500","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jep.2018.05.019","article-title":"Anti-inflammatory effects of luteolin: a review of in vitro, in vivo, and in silico studies","volume":"225","author":"Aziz","year":"2018","journal-title":"J Ethnopharmacol"},{"key":"10.1016\/j.drudis.2024.104026_b0505","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3389\/fimmu.2019.00051","article-title":"Immunomodulatory effects of flavonoids: possible induction of T CD4+ regulatory cells through suppression of mTOR pathway signaling activity","volume":"10","author":"Hosseinzade","year":"2019","journal-title":"Front Immunol"},{"key":"10.1016\/j.drudis.2024.104026_b0510","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1007\/s10600-015-1311-y","article-title":"Isolation and characterization of a new flavonoid glucoside from aerial parts of phrynium placentarium","volume":"51","author":"Utpal","year":"2015","journal-title":"Chem Nat Compd"},{"key":"10.1016\/j.drudis.2024.104026_b0515","doi-asserted-by":"crossref","first-page":"947","DOI":"10.3892\/ijo.2013.2009","article-title":"Polyphenols with indirect proprotein convertase inhibitory activity","volume":"43","author":"Zhu","year":"2013","journal-title":"Int J Oncol"},{"key":"10.1016\/j.drudis.2024.104026_b0520","first-page":"583","article-title":"Inhibition of tumor cells proliferation and migration by the flavonoid furin inhibitor isolated from Oroxylum indicum","volume":"20","author":"Lalou","year":"2013","journal-title":"Curr Med Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0525","article-title":"Phytopharmaceuticals mediated furin and TMPRSS2 receptor blocking: can it be a potential therapeutic option for Covid-19?","volume":"85","author":"Palit","year":"2020","journal-title":"Phytomedicine"},{"key":"10.1016\/j.drudis.2024.104026_b0530","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jep.2012.10.043","article-title":"Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines","volume":"145","author":"Chang","year":"2013","journal-title":"J Ethnopharmacol"},{"key":"10.1016\/j.drudis.2024.104026_b0535","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2023.115688","article-title":"Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin","volume":"215","author":"Yang","year":"2023","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.drudis.2024.104026_b0540","doi-asserted-by":"crossref","DOI":"10.1016\/j.antiviral.2020.104742","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","journal-title":"Antiviral Res"},{"key":"10.1016\/j.drudis.2024.104026_b0545","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s12250-020-00212-7","article-title":"A unique protease cleavage site predicted in the spike protein of the novel pneumonia coronavirus (2019-nCoV) potentially related to viral transmissibility","volume":"35","author":"Wang","year":"2020","journal-title":"Virol Sin"},{"key":"10.1016\/j.drudis.2024.104026_b0550","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2021.100794","article-title":"An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment","volume":"59","author":"Dro\u017cd\u017cal","year":"2021","journal-title":"Drug Resist Updat"},{"key":"10.1016\/j.drudis.2024.104026_b0555","article-title":"Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro","author":"Yamamoto","year":"2020","journal-title":"bioRxiv"},{"key":"10.1016\/j.drudis.2024.104026_b0560","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3855\/jidc.18","article-title":"Macrolides for the treatment of severe respiratory illness caused by novel H1N1 swine influenza viral strains","volume":"3","author":"Bermejo-Martin","year":"2009","journal-title":"J Infect Dev Ctries"},{"key":"10.1016\/j.drudis.2024.104026_b0565","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.2174\/15680266113136660223","article-title":"Structure-activity relationships and mechanism of action of macrolides derived from erythromycin as antibacterial agents","volume":"13","author":"Liang","year":"2013","journal-title":"Curr Top Med Chem"},{"key":"10.1016\/j.drudis.2024.104026_b0570","first-page":"2331","article-title":"New candidates for furin inhibition as probable treat for COVID-19: docking output","author":"Dayer","year":"2021","journal-title":"Ithaca"},{"issue":"10","key":"10.1016\/j.drudis.2024.104026_b0575","doi-asserted-by":"crossref","first-page":"101642","DOI":"10.1016\/j.isci.2020.101642","article-title":"Furin: a potential therapeutic target for COVID-19","volume":"23","author":"Wu","year":"2020","journal-title":"iScience"},{"key":"10.1016\/j.drudis.2024.104026_b0580","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jconrel.2020.10.009","article-title":"Ivermectin: an award-winning drug with expected antiviral activity against COVID-19","volume":"329","author":"Formiga","year":"2021","journal-title":"J Control Release"},{"key":"10.1016\/j.drudis.2024.104026_b0585","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1128\/AAC.48.7.2693-2696.2004","article-title":"Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide","volume":"48","author":"Wu","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"key":"10.1016\/j.drudis.2024.104026_b0590","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1016\/j.gendis.2022.12.019","article-title":"COVID-19 therapeutics: clinical application of repurposed drugs and futuristic strategies for target-based drug discovery","volume":"10","author":"Kumar","year":"2023","journal-title":"Genes Dis"}],"container-title":["Drug Discovery Today"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S135964462400151X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S135964462400151X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T19:33:19Z","timestamp":1720121599000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S135964462400151X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":118,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["S135964462400151X"],"URL":"https:\/\/doi.org\/10.1016\/j.drudis.2024.104026","relation":{},"ISSN":["1359-6446"],"issn-type":[{"value":"1359-6446","type":"print"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting furin, a cellular proprotein convertase, for COVID-19 prevention and therapeutics","name":"articletitle","label":"Article Title"},{"value":"Drug Discovery Today","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.drudis.2024.104026","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"104026"}}