{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:18:50Z","timestamp":1775276330779,"version":"3.50.1"},"reference-count":86,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.bmc.2021.116389","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T11:35:35Z","timestamp":1631619335000},"page":"116389","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection"],"prefix":"10.1016","volume":"48","author":[{"given":"Lukas","family":"Paulsson-Habegger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew K.","family":"Snabaitis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen P.","family":"Wren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2021.116389_b0005","doi-asserted-by":"crossref","unstructured":"Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The Species Severe Acute Respiratory Syndrome-Related Coronavirus: Classifying 2019-nCoV and Naming it SARS-CoV-2. Nat. Microbiol. 2020;5(4):536-44.","DOI":"10.1038\/s41564-020-0695-z"},{"key":"10.1016\/j.bmc.2021.116389_b0010","unstructured":"Who.int. 2020.Naming the Coronavirus Disease (COVID-19) and the Virus that Causes it. [online] Available at: <https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019\/technical-guidance\/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it>."},{"issue":"7","key":"10.1016\/j.bmc.2021.116389_b0015","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.00127-20","article-title":"Receptor Recognition by the Novel Coronavirus from Wuhan: An Analysis Based on Decade-Long Structural Studies of SARS Coronavirus","volume":"94","author":"Wan","year":"2020","journal-title":"J Virol"},{"key":"10.1016\/j.bmc.2021.116389_b0020","unstructured":"Covid19.who.int. 2020.WHO Coronavirus Disease (COVID-19) Dashboard. [online] Available at: <https:\/\/covid19.who.int\/>.[Date Accessed: 27\/05\/2021]."},{"issue":"20","key":"10.1016\/j.bmc.2021.116389_b0025","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1056\/NEJMoa030747","article-title":"Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome","volume":"348","author":"Drosten","year":"2003","journal-title":"New Eng J Med"},{"key":"10.1016\/j.bmc.2021.116389_b0030","unstructured":"Who.int. 2020.WHO | Summary of Probable SARS Cases with Onset of Illness From 1 November 2002 To 31 July 2003. [online] Available at: <https:\/\/www.who.int\/csr\/sars\/country\/table2004_04_21\/en\/>."},{"key":"10.1016\/j.bmc.2021.116389_b0035","unstructured":"World Health Organization. 2020. Middle East Respiratory Syndrome Coronavirus (MERS-Cov). [online] Available at: <https:\/\/www.who.int\/emergencies\/mers-cov\/en\/>."},{"key":"10.1016\/j.bmc.2021.116389_b0040","article-title":"Correlation Between Relative Nasopharyngeal Virus RNA Load and Lymphocyte Count Disease Severity in Patients with COVID-19","author":"Liu","year":"2020","journal-title":"Viral Immunol."},{"issue":"4","key":"10.1016\/j.bmc.2021.116389_b0045","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1007\/s00134-020-05985-9","article-title":"Angiotensin-Converting Enzyme 2 (ACE2) as a SARS-CoV-2 Receptor: Molecular Mechanisms and Potential Therapeutic Target","volume":"46","author":"Zhang","year":"2020","journal-title":"Intens Care Med"},{"issue":"5","key":"10.1016\/j.bmc.2021.116389_b0050","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1172\/JCI137647","article-title":"SARS-CoV-2: A Storm is Raging","volume":"130","author":"Pedersen","year":"2020","journal-title":"J Clin Invest."},{"issue":"16","key":"10.1016\/j.bmc.2021.116389_b0055","doi-asserted-by":"crossref","first-page":"8801","DOI":"10.1128\/JVI.77.16.8801-8811.2003","article-title":"The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core Complex","volume":"77","author":"Bosch","year":"2003","journal-title":"J Virol"},{"key":"10.1016\/j.bmc.2021.116389_b0060","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/bs.aivir.2019.08.002","article-title":"Structural Insights into Coronavirus Entry","volume":"105","author":"Tortorici","year":"2019","journal-title":"Adv Virus Res"},{"issue":"2","key":"10.1016\/j.bmc.2021.116389_b0065","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"},{"issue":"1","key":"10.1016\/j.bmc.2021.116389_b0070","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":"Ann Rev Virol"},{"issue":"21","key":"10.1016\/j.bmc.2021.116389_b0075","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"},{"issue":"6485","key":"10.1016\/j.bmc.2021.116389_b0080","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural Basis for the Recognition of SARS-CoV-2 by Full-Length Human ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"issue":"9","key":"10.1016\/j.bmc.2021.116389_b0085","doi-asserted-by":"crossref","first-page":"e202000786","DOI":"10.26508\/lsa.202000786","article-title":"TMPRSS2 and Furin are Both Essential for Proteolytic Activation of SARS-CoV-2 in Human Airway Cells","volume":"3","author":"Bestle","year":"2020","journal-title":"Life Sci Alliance"},{"issue":"4","key":"10.1016\/j.bmc.2021.116389_b0090","doi-asserted-by":"crossref","first-page":"557","DOI":"10.3390\/v4040557","article-title":"Ready, Set, Fuse! The Coronavirus Spike Protein and Acquisition of Fusion Competence","volume":"4","author":"Heald-Sargent","year":"2012","journal-title":"Viruses"},{"issue":"4","key":"10.1016\/j.bmc.2021.116389_b0095","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.bmc.2021.116389_b0100","series-title":"Activation of Viruses by Host Proteases","year":"2018"},{"issue":"10","key":"10.1016\/j.bmc.2021.116389_b0105","doi-asserted-by":"crossref","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."},{"issue":"7837","key":"10.1016\/j.bmc.2021.116389_b0110","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41586-020-2772-0","article-title":"Receptor Binding and Priming of the Spike Protein of SARS-CoV-2 for Membrane Fusion","volume":"588","author":"Benton","year":"2020","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.bmc.2021.116389_b0115","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.bmc.2021.116389_b0120","unstructured":"TMPRSS2 Transmembrane Serine Protease 2 [Homo sapiens (human)] - Gene - NCBI [Internet]. National Center for Biotechnology Information. 2021 [cited 18 February 2021]. Available from: https:\/\/www.ncbi.nlm.nih.gov\/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7113."},{"key":"10.1016\/j.bmc.2021.116389_b0125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biochi.2017.07.016","article-title":"TMPRSS2: A Potential Target for Treatment of Influenza Virus and Coronavirus Infections","volume":"142","author":"Shen","year":"2017","journal-title":"Biochimie"},{"issue":"3","key":"10.1016\/j.bmc.2021.116389_b0130","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1006\/geno.1997.4845","article-title":"Cloning of the TMPRSS2 Gene, Which Encodes a Novel Serine Protease with Transmembrane, LDLRA, and SRCR Domains and Maps to 21q22.3","volume":"44","author":"Paoloni-Giacobino","year":"1997","journal-title":"Genomics"},{"issue":"11","key":"10.1016\/j.bmc.2021.116389_b0135","doi-asserted-by":"crossref","first-page":"5605","DOI":"10.1128\/JVI.00140-10","article-title":"Cleavage of Influenza Virus Hemagglutinin by Airway Proteases TMPRSS2 and HAT Differs in Subcellular Localization and Susceptibility to Protease Inhibitors","volume":"84","author":"B\u00f6ttcher-Friebertsh\u00e4user","year":"2010","journal-title":"J Virology"},{"issue":"11","key":"10.1016\/j.bmc.2021.116389_b0140","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1158\/2159-8290.CD-13-1010","article-title":"The Androgen-Regulated Protease TMPRSS2 Activates a Proteolytic Cascade Involving Components of the Tumor Microenvironment and Promotes Prostate Cancer Metastasis","volume":"4","author":"Lucas","year":"2014","journal-title":"Cancer Discov"},{"issue":"6","key":"10.1016\/j.bmc.2021.116389_b0145","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3390\/v4061011","article-title":"Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein","volume":"4","author":"Belouzard","year":"2012","journal-title":"Viruses"},{"issue":"6511","key":"10.1016\/j.bmc.2021.116389_b0150","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abd4251","article-title":"Distinct Conformational States of SARS-CoV-2 Spike Protein","volume":"369","author":"Cai","year":"2020","journal-title":"Science"},{"issue":"42","key":"10.1016\/j.bmc.2021.116389_b0155","doi-asserted-by":"crossref","first-page":"11157","DOI":"10.1073\/pnas.1708727114","article-title":"Tectonic Conformational Changes of a Coronavirus Spike Glycoprotein Promote Membrane Fusion","volume":"114","author":"Walls","year":"2017","journal-title":"Proc Natl Acad Sci"},{"issue":"8","key":"10.1016\/j.bmc.2021.116389_b0160","doi-asserted-by":"crossref","first-page":"e1007236","DOI":"10.1371\/journal.ppat.1007236","article-title":"Cryo-EM Structure of the SARS Coronavirus Spike Glycoprotein in Complex with its Host Cell Receptor ACE2","volume":"14","author":"Song","year":"2018","journal-title":"PLOS Path."},{"issue":"6","key":"10.1016\/j.bmc.2021.116389_b0165","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/tra.12389","article-title":"Fusion of Enveloped Viruses in Endosomes","volume":"17","author":"White","year":"2016","journal-title":"Traffic"},{"issue":"8","key":"10.1016\/j.bmc.2021.116389_b0170","doi-asserted-by":"crossref","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","journal-title":"Nat Med"},{"issue":"2","key":"10.1016\/j.bmc.2021.116389_b0175","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1128\/JVI.01248-09","article-title":"Differential Downregulation of ACE2 by the Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus and Human Coronavirus NL63","volume":"84","author":"Glowacka","year":"2010","journal-title":"J Virol"},{"issue":"5","key":"10.1016\/j.bmc.2021.116389_b0180","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A Novel Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1\u20139","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ Res"},{"issue":"8","key":"10.1016\/j.bmc.2021.116389_b0185","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1161\/CIRCRESAHA.116.307708","article-title":"Role of the ACE2\/Angiotensin 1\u20137 Axis of the Renin-Angiotensin System in Heart Failure","volume":"118","author":"Patel","year":"2016","journal-title":"Circ Res"},{"issue":"21","key":"10.1016\/j.bmc.2021.116389_b0190","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0960-9822(02)01255-1","article-title":"Just the Beginning: Novel Functions for Angiotensin-Converting Enzymes","volume":"12","author":"Eriksson","year":"2002","journal-title":"Curr Biol"},{"key":"10.1016\/j.bmc.2021.116389_b0195","unstructured":"Acton S, Robison K, 2001. Angiotensin Converting Enzyme Homolog and Therapeutic and Diagnostic Uses Therefor. US 6,194,556 B1."},{"issue":"14","key":"10.1016\/j.bmc.2021.116389_b0200","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1111\/j.1742-4658.2005.04756.x","article-title":"Identification of Critical Active-Site Residues in Angiotensin-Converting Enzyme-2 (ACE2) by Site-Directed Mutagenesis","volume":"272","author":"Guy","year":"2005","journal-title":"FEBS J"},{"issue":"9","key":"10.1016\/j.bmc.2021.116389_b0205","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1271\/bbb.130360","article-title":"Effects of Conversion of the Zinc-Binding Motif Sequence of Thermolysin, HEXXH, to That of Dipeptidyl Peptidase III, HEXXXH, on the Activity and Stability of Thermolysin","volume":"77","author":"Menach","year":"2013","journal-title":"Biosci Biotechnol Biochem"},{"key":"10.1016\/j.bmc.2021.116389_b0210","unstructured":"PDB ID: 1R42, Towler P, Staker B, Prasad S, Menon S, Ryan D, Tang J et al. Native Human Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2). J Biol Chem 2004;279(17):17996-18007. Mol* (D. Sehnal, A.S. Rose, J. Kovca, S.K. Burley, S. Velankar (2018) Mol*: Towards a Common Library and Tools for Web Molecular Graphics MolVA\/EuroVis Proceedings. doi:10.2312\/molva.20181103)."},{"issue":"8 Supp B","key":"10.1016\/j.bmc.2021.116389_b0215","first-page":"9","article-title":"The Renin-Angiotensin Aldosterone System: Pathophysiological Role and Pharmacologic Inhibition","volume":"13","author":"Atlas","year":"2007","journal-title":"J. Manag. Care Spec. Pharm."},{"issue":"4","key":"10.1016\/j.bmc.2021.116389_b0220","doi-asserted-by":"crossref","first-page":"F486","DOI":"10.1152\/ajprenal.1991.260.4.F486","article-title":"Renin Release from Isolated Juxtaglomerular Apparatus Depends on Macula Densa Chloride Transport","volume":"260","author":"Lorenz","year":"1991","journal-title":"Am J Physiol-Renal"},{"issue":"2","key":"10.1016\/j.bmc.2021.116389_b0225","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0014-5793(98)01145-4","article-title":"Angiotensinogen Cleavage by Renin: Importance of a Structurally Constrained N-terminus","volume":"436","author":"Streatfeild-James","year":"1998","journal-title":"FEBS Lett"},{"issue":"7","key":"10.1016\/j.bmc.2021.116389_b0230","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/hr.2016.17","article-title":"Structure and Functions of Angiotensinogen","volume":"39","author":"Lu","year":"2016","journal-title":"Hypertens Res"},{"issue":"3","key":"10.1016\/j.bmc.2021.116389_b0235","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1210\/er.2003-0001","article-title":"Newly Recognized Components of the Renin-Angiotensin System: Potential Roles in Cardiovascular and Renal Regulation","volume":"24","author":"Carey","year":"2003","journal-title":"Endocr Rev"},{"issue":"3","key":"10.1016\/j.bmc.2021.116389_b0240","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/j.1365-2796.2008.01981.x","article-title":"Renin-Angiotensin System Revisited","volume":"264","author":"Fyhrquist","year":"2008","journal-title":"J Intern Med"},{"key":"10.1016\/j.bmc.2021.116389_b0245","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.peptides.2016.09.009","article-title":"Angiotensin-(1\u20135), an Active Mediator of Renin-Angiotensin System, Stimulates ANP Secretion via Mas Receptor","volume":"86","author":"Yu","year":"2016","journal-title":"Peptides"},{"key":"10.1016\/j.bmc.2021.116389_b0250","unstructured":"PubChem Compound Summary for CID 3082042, Angiotensin III [Internet]. National Center for Biotechnology Information. 2021 [cited 18 February 2021]. Available from: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/angiotensin_iii."},{"issue":"3","key":"10.1016\/j.bmc.2021.116389_b0255","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1161\/01.HYP.0000196950.48596.21","article-title":"Renal Angiotensin Type 2 Receptors Mediate Natriuresis Via Angiotensin III in the Angiotensin II Type 1 Receptor-Blocked Rat","volume":"47","author":"Padia","year":"2006","journal-title":"Hypertension"},{"issue":"21","key":"10.1016\/j.bmc.2021.116389_b0260","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1007\/s00018-004-4246-1","article-title":"What's New in the Renin-Angiotensin System?","volume":"61","author":"Chai","year":"2004","journal-title":"Cell Mol Life Sci"},{"issue":"1","key":"10.1016\/j.bmc.2021.116389_b0265","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/S0165-0173(97)00019-2","article-title":"Important Roles for Angiotensin III and IV in the Brain Renin-Angiotensin System","volume":"25","author":"Wright","year":"1997","journal-title":"Brain Res Rev"},{"issue":"5","key":"10.1016\/j.bmc.2021.116389_b0270","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1113\/expphysiol.2008.042002","article-title":"Recent Advances in the Angiotensin-Converting Enzyme 2 - Angiotensin-(1\u20137) - Mas Axis","volume":"93","author":"Santos","year":"2008","journal-title":"Exp. Physiol."},{"issue":"1","key":"10.1016\/j.bmc.2021.116389_b0275","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1161\/HYPERTENSIONAHA.109.143255","article-title":"Angiotensin-(1\u20137) Prevents Cardiomyocyte Pathological Remodeling Through a Nitric Oxide\/Guanosine 3\u2032,5\u2032-Cyclic Monophosphate-Dependent Pathway","volume":"55","author":"Gomes","year":"2010","journal-title":"Hypertension"},{"key":"10.1016\/j.bmc.2021.116389_b0280","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejphar.2016.01.007","article-title":"Angiotensin Converting Enzyme versus Angiotensin Converting Enzyme-2 Selectivity of MLN-4760 and DX600 in Human and Murine Bone Marrow-Derived Cells","volume":"774","author":"Joshi","year":"2016","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.bmc.2021.116389_b0285","doi-asserted-by":"crossref","unstructured":"Daina A, Michielin O, Zoete V. SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules. Sci Rep 7(1).","DOI":"10.1038\/srep42717"},{"issue":"18","key":"10.1016\/j.bmc.2021.116389_b0290","doi-asserted-by":"crossref","first-page":"15532","DOI":"10.1074\/jbc.M212934200","article-title":"Novel Peptide Inhibitors of Angiotensin-Converting Enzyme 2","volume":"278","author":"Huang","year":"2003","journal-title":"J Biol Chem"},{"issue":"40","key":"10.1016\/j.bmc.2021.116389_b0295","doi-asserted-by":"crossref","first-page":"11852","DOI":"10.1021\/ja0277226","article-title":"Substrate-Based Design of the First Class of Angiotensin-Converting Enzyme-Related Carboxypeptidase (ACE2) Inhibitors","volume":"124","author":"Dales","year":"2002","journal-title":"J Am Chem Soc"},{"issue":"20","key":"10.1016\/j.bmc.2021.116389_b0300","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1002\/cmdc.201600288","article-title":"Oral Administration of Peptide-Based Drugs: Beyond Lipinski's Rule","volume":"11","author":"Santos","year":"2016","journal-title":"ChemMedChem"},{"issue":"6","key":"10.1016\/j.bmc.2021.116389_b0305","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1161\/01.HYP.0000146120.29648.36","article-title":"Structure-Based Discovery of a Novel Angiotensin-Converting Enzyme 2 Inhibitor","volume":"44","author":"Huentelman","year":"2004","journal-title":"Hypertension"},{"key":"10.1016\/j.bmc.2021.116389_b0310","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmgm.2020.107697","article-title":"Prioritizing Potential ACE2 Inhibitors in the COVID-19 Pandemic: Insights from a Molecular Mechanics-Assisted Structure-Based Virtual Screening Experiment","volume":"100","author":"Teral\u0131","year":"2020","journal-title":"J Mol Graph Model"},{"issue":"16","key":"10.1016\/j.bmc.2021.116389_b0315","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.1016\/j.bmcl.2011.06.091","article-title":"New substrate analogue furin inhibitors derived from 4-amidinobenzylamide","volume":"21","author":"Becker","year":"2011","journal-title":"Bioorg Med Chem Lett"},{"issue":"3","key":"10.1016\/j.bmc.2021.116389_b0320","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"},{"issue":"12","key":"10.1016\/j.bmc.2021.116389_b0325","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1021\/cr010182v","article-title":"Irreversible Inhibitors of Serine, Cysteine, and Threonine Proteases","volume":"102","author":"Powers","year":"2002","journal-title":"Chem Rev"},{"issue":"26","key":"10.1016\/j.bmc.2021.116389_b0330","doi-asserted-by":"crossref","first-page":"21992","DOI":"10.1074\/jbc.M111.332643","article-title":"Highly Potent Inhibitors of Proprotein Convertase Furin as Potential Drugs for Treatment of Infectious Diseases","volume":"287","author":"Becker","year":"2012","journal-title":"J Biol Chem"},{"issue":"12","key":"10.1016\/j.bmc.2021.116389_b0335","doi-asserted-by":"crossref","first-page":"6537","DOI":"10.1128\/JVI.00094-12","article-title":"Simultaneous Treatment of Human Bronchial Epithelial Cells with Serine and Cysteine Protease Inhibitors Prevents Severe Acute Respiratory Syndrome Coronavirus Entry","volume":"86","author":"Kawase","year":"2012","journal-title":"J Virol"},{"key":"10.1016\/j.bmc.2021.116389_b0340","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pupt.2015.07.001","article-title":"The Serine Protease Inhibitor Camostat Inhibits Influenza Virus Replication and Cytokine Production in Primary Cultures of Human Tracheal Epithelial Cells","volume":"33","author":"Yamaya","year":"2015","journal-title":"Pulm Pharmacol Ther"},{"key":"10.1016\/j.bmc.2021.116389_b0345","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.antiviral.2015.01.011","article-title":"Protease Inhibitors Targeting Coronavirus and Filovirus Entry","volume":"116","author":"Zhou","year":"2015","journal-title":"Antivir. Res."},{"issue":"2","key":"10.1016\/j.bmc.2021.116389_b0350","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1042\/BJ20130101","article-title":"Identification of the First Synthetic Inhibitors of the Type II Transmembrane Serine Protease TMPRSS2 Suitable for Inhibition of Influenza Virus Activation","volume":"452","author":"Meyer","year":"2013","journal-title":"Biochem J"},{"issue":"45","key":"10.1016\/j.bmc.2021.116389_b0355","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1016\/j.vaccine.2009.03.029","article-title":"MDCK Cells that Express Proteases TMPRSS2 and HAT Provide a Cell System to Propagate Influenza Viruses in the Absence of Trypsin and to Study Cleavage of HA and its Inhibition","volume":"27","author":"B\u00f6ttcher","year":"2009","journal-title":"Vaccine"},{"issue":"16","key":"10.1016\/j.bmc.2021.116389_b0360","doi-asserted-by":"crossref","first-page":"4860","DOI":"10.1016\/j.bmcl.2011.06.033","article-title":"Development of Substrate Analogue Inhibitors for the Human Airway Trypsin-like Protease HAT","volume":"21","author":"Sielaff","year":"2011","journal-title":"Bioorg Med Chem Lett"},{"issue":"13","key":"10.1016\/j.bmc.2021.116389_b0365","doi-asserted-by":"crossref","first-page":"6094","DOI":"10.1021\/jm300337q","article-title":"Ligand Binding Stepwise Disrupts Water Network in Thrombin: Enthalpic and Entropic Changes Reveal Classical Hydrophobic Effect","volume":"55","author":"Biela","year":"2012","journal-title":"J Med Chem"},{"issue":"15","key":"10.1016\/j.bmc.2021.116389_b0370","doi-asserted-by":"crossref","first-page":"5523","DOI":"10.1021\/jm100183e","article-title":"Identification of the First Low-Molecular-Weight Inhibitors of Matriptase-2","volume":"53","author":"Sisay","year":"2010","journal-title":"J Med Chem"},{"issue":"6","key":"10.1016\/j.bmc.2021.116389_b0375","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1021\/jm960762y","article-title":"Design of Highly Potent Noncovalent Thrombin Inhibitors That Utilize a Novel Lipophilic Binding Pocket in the Thrombin Active Site","volume":"40","author":"Tucker","year":"1997","journal-title":"J Med Chem"},{"issue":"14","key":"10.1016\/j.bmc.2021.116389_b0380","doi-asserted-by":"crossref","first-page":"4116","DOI":"10.1021\/jm051272l","article-title":"Secondary Amides of Sulfonylated 3-Amidinophenylalanine. New Potent and Selective Inhibitors of Matriptase\u2020","volume":"49","author":"Steinmetzer","year":"2006","journal-title":"J Med Chem"},{"issue":"1","key":"10.1016\/j.bmc.2021.116389_b0385","first-page":"87","article-title":"Structure-Actmty Relationships of Inhibitors Derived from 3-Amidinophenylalanine","volume":"9","author":"St\u00fcrzebecher","year":"1995","journal-title":"J Enzyme Inhib Med Chem"},{"issue":"1","key":"10.1016\/j.bmc.2021.116389_b0390","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3109\/00498259409043223","article-title":"Metabolic Fate of 14C-Camostat Mesylate in Man, Rat and Dog After Intravenous Administration","volume":"24","author":"Midgley","year":"1994","journal-title":"Xenobiotica"},{"issue":"2","key":"10.1016\/j.bmc.2021.116389_b0395","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/bcpt.13533","article-title":"Camostat Mesylate Against SARS-CoV-2 and COVID-19\u2014Rationale, Dosing and Safety","volume":"128","author":"Breining","year":"2020","journal-title":"Basic Clin Pharmacol"},{"key":"10.1016\/j.bmc.2021.116389_b0400","doi-asserted-by":"crossref","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","journal-title":"EBioMedicine"},{"key":"10.1016\/j.bmc.2021.116389_b0405","unstructured":"Search of: Camostat | Covid19 - List Results - ClinicalTrials.gov [Internet]. National Institute of Health. 2021 [cited 18 February 2021]. Available from: https:\/\/www.clinicaltrials.gov\/ct2\/results?recrs=&cond=Covid19&term=camostat&cntry=&state=&city=&dist=."},{"issue":"5","key":"10.1016\/j.bmc.2021.116389_b0410","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s11739-020-02383-3","article-title":"Potential New Treatment Strategies for COVID-19: Is There a Role for Bromhexine as Add-on Therapy?","volume":"15","author":"Depfenhart","year":"2020","journal-title":"Intern Emerg Med"},{"issue":"6","key":"10.1016\/j.bmc.2021.116389_b0415","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijantimicag.2020.106192","article-title":"Azithromycin and Ambroxol as Potential Pharmacotherapy for SARS-CoV-2","volume":"56","author":"Alkotaji","year":"2020","journal-title":"Int J Antimicrob Agents"},{"issue":"1","key":"10.1016\/j.bmc.2021.116389_b0420","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1021\/acs.bioconjchem.0c00664","article-title":"Rationally Designed ACE2-Derived Peptides Inhibit SARS-CoV-2","volume":"32","author":"Larue","year":"2021","journal-title":"Bioconjug Chem"},{"issue":"2","key":"10.1016\/j.bmc.2021.116389_b0425","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s12195-020-00658-5","article-title":"Structure-Based Design of Novel Peptidomimetics Targeting the SARS-CoV-2 Spike Protein","volume":"14","author":"Alagumuthu","year":"2020","journal-title":"Cell Mol Bioeng"},{"issue":"18","key":"10.1016\/j.bmc.2021.116389_b0430","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.4155\/fmc-2020-0180","article-title":"Evidence supporting the use of peptides and peptidomimetics as potential SARS-CoV-2 (COVID-19) therapeutics","volume":"12","author":"VanPatten","year":"2020","journal-title":"Future Med. Chem."}],"container-title":["Bioorganic &amp; Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089621003977?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089621003977?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T01:14:35Z","timestamp":1760836475000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089621003977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":86,"alternative-id":["S0968089621003977"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2021.116389","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Enzyme inhibition as a potential therapeutic strategy to treat COVID-19 infection","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2021.116389","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"116389"}}