{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:08:59Z","timestamp":1782436139364,"version":"3.54.5"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU Research Framework Programme H2020\/Marie Sk\u0142odowska-Curie Actions","award":["101024974"],"award-info":[{"award-number":["101024974"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>SARS-CoV-2 is the pathogen responsible for the most recent global pandemic, which has claimed hundreds of thousands of victims worldwide. Despite remarkable efforts to develop an effective vaccine, concerns have been raised about the actual protection against novel variants. Thus, researchers are eager to identify alternative strategies to fight against this pathogen. Like other opportunistic entities, a key step in the SARS-CoV-2 lifecycle is the maturation of the envelope glycoprotein at the RARR685\u2193 motif by the cellular enzyme Furin. Inhibition of this cleavage greatly affects viral propagation, thus representing an ideal drug target to contain infection. Importantly, no Furin-escape variants have ever been detected, suggesting that the pathogen cannot replace this protease by any means. Here, we designed a novel fluorogenic SARS-CoV-2-derived substrate to screen commercially available and custom-made libraries of small molecules for the identification of new Furin inhibitors. We found that a peptide substrate mimicking the cleavage site of the envelope glycoprotein of the Omicron variant (QTQTKSHRRAR-AMC) is a superior tool for screening Furin activity when compared to the commercially available Pyr-RTKR-AMC substrate. Using this setting, we identified promising novel compounds able to modulate Furin activity in vitro and suitable for interfering with SARS-CoV-2 maturation. In particular, we showed that 3-((5-((5-bromothiophen-2-yl)methylene)-4-oxo-4,5 dihydrothiazol-2-yl)(3-chloro-4-methylphenyl)amino)propanoic acid (P3, IC50 = 35 \u03bcM) may represent an attractive chemical scaffold for the development of more effective antiviral drugs via a mechanism of action that possibly implies the targeting of Furin secondary sites (exosites) rather than its canonical catalytic pocket. Overall, a SARS-CoV-2-derived peptide was investigated as a new substrate for in vitro high-throughput screening (HTS) of Furin inhibitors and allowed the identification of compound P3 as a promising hit with an innovative chemical scaffold. Given the key role of Furin in infection and the lack of any Food and Drug Administration (FDA)-approved Furin inhibitor, P3 represents an interesting antiviral candidate.<\/jats:p>","DOI":"10.3390\/ijms25105079","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T09:03:38Z","timestamp":1715072618000},"page":"5079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Screening of Small-Molecule Libraries Using SARS-CoV-2-Derived Sequences Identifies Novel Furin Inhibitors"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6595-5125","authenticated-orcid":false,"given":"Alireza","family":"Jorkesh","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Science, University of Padova, Via Marzolo, 5, 35131 Padova, Italy"},{"name":"Department of Biology, University of Padua, Viale G. Colombo 3, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8633-2994","authenticated-orcid":false,"given":"Sylvia","family":"Rothenberger","sequence":"additional","affiliation":[{"name":"Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, 1011 Lausanne, Switzerland"},{"name":"Spiez Laboratory, Federal Office for Civil Protection, Austrasse, 3700 Spiez, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Baldassar","sequence":"additional","affiliation":[{"name":"Department of Industrial Engineering, University of Padova, Via Marzolo 9, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0982-1342","authenticated-orcid":false,"given":"Birute","family":"Grybaite","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu Rd. 19, LT-50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0237-9088","authenticated-orcid":false,"given":"Povilas","family":"Kavaliauskas","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu Rd. 19, LT-50254 Kaunas, Lithuania"},{"name":"Joan and Sanford I. Weill Department of Medicine, Weill Cornell University, 1300 York Avenue, New York, NY 10065, USA"},{"name":"Biological Research Center, Lithuanian University of Health Sciences, Tilzes Str. 18, LT-47181 Kaunas, Lithuania"},{"name":"Institute of Infectious Diseases and Pathogenic Microbiology, Birstono Str. 38A, LT-59116 Prienai, Lithuania"},{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-2941","authenticated-orcid":false,"given":"Vytautas","family":"Mickevicius","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Kaunas University of Technology, Radvilenu Rd. 19, LT-50254 Kaunas, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6823-3375","authenticated-orcid":false,"given":"Monica","family":"Dettin","sequence":"additional","affiliation":[{"name":"Department of Industrial Engineering, University of Padova, Via Marzolo 9, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5747-507X","authenticated-orcid":false,"given":"Filippo","family":"Vascon","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padua, Viale G. Colombo 3, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-0461","authenticated-orcid":false,"given":"Laura","family":"Cendron","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padua, Viale G. Colombo 3, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-0722","authenticated-orcid":false,"given":"Antonella","family":"Pasquato","sequence":"additional","affiliation":[{"name":"Department of Industrial Engineering, University of Padova, Via Marzolo 9, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1056\/NEJMp1905224","article-title":"Preparing for the Next Pandemic\u2014The WHO\u2019s Global Influenza Strategy","volume":"381","author":"Phelan","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/s41591-020-0796-5","article-title":"Emergence of a Novel Human Coronavirus Threatening Human Health","volume":"26","author":"Poon","year":"2020","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(21)02796-3","article-title":"Estimating Excess Mortality Due to the COVID-19 Pandemic: A Systematic Analysis of COVID-19-Related Mortality, 2020\u20132021","volume":"399","author":"Wang","year":"2022","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e236","DOI":"10.1016\/S2666-5247(22)00390-1","article-title":"Efficacy of SARS-CoV-2 Vaccines and the Dose\u2013Response Relationship with Three Major Antibodies: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"4","author":"Yang","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"317","DOI":"10.14740\/jocmr4518","article-title":"Review of COVID-19 Variants and COVID-19 Vaccine Efficacy: What the Clinician Should Know?","volume":"13","author":"Vasireddy","year":"2021","journal-title":"J. Clin. Med. Res."},{"key":"ref_7","unstructured":"Aleem, A., Akbar Samad, A.B., and Vaqar, S. (2024). StatPearls, StatPearls Publishing."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104742","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":"Antivir. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nrd3699","article-title":"The Biology and Therapeutic Targeting of the Proprotein Convertases","volume":"11","author":"Seidah","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apcsb.2022.10.001","article-title":"Chapter One\u2014Proprotein Convertases Regulate Trafficking and Maturation of Key Proteins within the Secretory Pathway","volume":"Volume 133","author":"Donev","year":"2023","journal-title":"Advances in Protein Chemistry and Structural Biology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Seidah, N.G., Pasquato, A., and Andr\u00e9o, U. (2021). How Do Enveloped Viruses Exploit the Secretory Proprotein Convertases to Regulate Infectivity and Spread?. Viruses, 13.","DOI":"10.20944\/preprints202104.0469.v1"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cassari, L., Pavan, A., Zoia, G., Chinellato, M., Zeni, E., Grinzato, A., Rothenberger, S., Cendron, L., Dettin, M., and Pasquato, A. (2023). SARS-CoV-2 S Mutations: A Lesson from the Viral World to Understand How Human Furin Works. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054791"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lubinski, B., Jaimes, J.A., and Whittaker, G.R. (2022). Whittaker Intrinsic Furin-Mediated Cleavability of the Spike S1\/S2 Site from SARS-CoV-2 Variant B.1.1.529 (Omicron). bioRxiv, bioRxiv:2022.04.20.488969.","DOI":"10.1101\/2022.04.20.488969"},{"key":"ref_14","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":"ref_15","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":"ref_16","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1002\/jmv.27539","article-title":"Roles of the Polybasic Furin Cleavage Site of Spike Protein in SARS-CoV-2 Replication, Pathogenesis, and Host Immune Responses and Vaccination","volume":"94","author":"Hossain","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2109905118","DOI":"10.1073\/pnas.2109905118","article-title":"Furin Cleavage of the SARS-CoV-2 Spike Is Modulated by O-Glycosylation","volume":"118","author":"Zhang","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chan, Y.A., and Zhan, S.H. (2022). The Emergence of the Spike Furin Cleavage Site in SARS-CoV-2. Mol. Biol. Evol., 39.","DOI":"10.1093\/molbev\/msab327"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Reuter, N., Chen, X., Kropff, B., Peter, A.S., Britt, W.J., Mach, M., \u00dcberla, K., and Thomas, M. (2023). SARS-CoV-2 Spike Protein Is Capable of Inducing Cell\u2013Cell Fusions Independent from Its Receptor ACE2 and This Activity Can Be Impaired by Furin Inhibitors or a Subset of Monoclonal Antibodies. Viruses, 15.","DOI":"10.3390\/v15071500"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00128-22","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":"ref_21","doi-asserted-by":"crossref","first-page":"108254","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":"ref_22","first-page":"162","article-title":"SARS-CoV-2 Variant Biology: Immune Escape, Transmission and Fitness","volume":"21","author":"Carabelli","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2022.01.002","article-title":"A Novel Antibody against the Furin Cleavage Site of SARS-CoV-2 Spike Protein: Effects on Proteolytic Cleavage and ACE2 Binding","volume":"242","author":"Spelios","year":"2022","journal-title":"Immunol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, L., Gao, M., Li, J., Xie, X., Zhao, H., Wang, Y., Xu, X., Zu, S., Chen, C., and Wan, D. (2023). Identification of an Immunogenic Epitope and Protective Antibody against the Furin Cleavage Site of SARS-CoV-2. eBioMedicine, 87.","DOI":"10.1016\/j.ebiom.2022.104401"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1042\/BJ20120537","article-title":"Generation and Characterization of Non-Competitive Furin-Inhibiting Nanobodies","volume":"448","author":"Zhu","year":"2012","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7293","DOI":"10.1073\/pnas.95.13.7293","article-title":"A1-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. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1042\/BST20230078","article-title":"Alpha-1-Antitrypsin Antagonizes COVID-19: A Review of the Epidemiology, Molecular Mechanisms, and Clinical Evidence","volume":"51","author":"Bai","year":"2023","journal-title":"Biochem. Soc. Trans."},{"key":"ref_28","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. USA"},{"key":"ref_29","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":"ref_30","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"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.chembiol.2022.02.001","article-title":"A Highly Selective, Cell-Permeable Furin Inhibitor BOS-318 Rescues Key Features of Cystic Fibrosis Airway Disease","volume":"29","author":"Douglas","year":"2022","journal-title":"Cell Chem. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Thomas, G., Couture, F., and Kwiatkowska, A. (2022). The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073435"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23471","DOI":"10.1074\/jbc.M513675200","article-title":"The Proprotein Convertase SKI-1\/S1P: In Vitro Analysis of Lassa Virus Glycoprotein-Derived Substrates and Ex Vivo Validation of Irreversible Peptide Inhibitors","volume":"281","author":"Pasquato","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.virol.2011.04.021","article-title":"Arenavirus Envelope Glycoproteins Mimic Autoprocessing Sites of the Cellular Proprotein Convertase Subtilisin Kexin Isozyme-1\/Site-1 Protease","volume":"417","author":"Pasquato","year":"2011","journal-title":"Virology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"20897","DOI":"10.1074\/jbc.M803762200","article-title":"Substrate Cleavage Analysis of Furin and Related Proprotein Convertases: A Comparative Study*","volume":"283","author":"Remacle","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1006\/abbi.1996.0249","article-title":"Purification and Enzymatic Characterization of Recombinant Prohormone Convertase 2: Stabilization of Activity by 21 kDa 7B2","volume":"330","author":"Lamango","year":"1996","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.2174\/092986712801323162","article-title":"Limitations of Inhibitory Activities of Polyphenols on Furin-Mediated Substrate Processing","volume":"19","author":"Zhu","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1007\/s11418-021-01519-9","article-title":"Screening for Inhibitory Effects of Crude Drugs on Furin-like Enzymatic Activities","volume":"75","author":"Kiba","year":"2021","journal-title":"J. Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays","volume":"4","author":"Zhang","year":"1999","journal-title":"SLAS Discov."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Le Guilloux, V., Schmidtke, P., and Tuffery, P. (2009). Fpocket: An Open Source Platform for Ligand Pocket Detection. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-168"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Feng, D., Ren, L., Wu, J., Guo, L., Han, Z., Yang, J., Xie, W., Wang, Y., Xu, F., and Su, X. (2023). Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition. Molecules, 28.","DOI":"10.3390\/molecules28041883"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100951","DOI":"10.1016\/j.imu.2022.100951","article-title":"Unravelling Vitamin B12 as a Potential Inhibitor against SARS-CoV-2: A Computational Approach","volume":"30","author":"Pandya","year":"2022","journal-title":"Inform. Med. Unlocked"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.4254\/wjh.v14.i6.1131","article-title":"COVID-19 Liver and Gastroenterology Findings: An in Silico Analysis of SARS-CoV-2 Interactions with Liver Molecules","volume":"14","author":"Peiter","year":"2022","journal-title":"WJH"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rajak, P., and Ganguly, A. (2023). In Silico Study Unfolds Inhibitory Potential of Epicatechin Gallate against SARS-CoV-2 Entry and Replication within the Host Cell. Mechanobiol. Med., 1.","DOI":"10.1016\/j.mbm.2023.100015"},{"key":"ref_48","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":"ref_49","doi-asserted-by":"crossref","first-page":"30442","DOI":"10.1074\/jbc.271.48.30442","article-title":"Identification of the Paired Basic Convertases Implicated in HIV Gp160 Processing Based on in Vitro Assays and Expression in CD4+ Cell Lines","volume":"271","author":"Decroly","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1007\/s00706-013-1074-8","article-title":"Synthesis and Antimicrobial Activity of N-(4-Chlorophenyl)-\u03b2-Alanine Derivatives with an Azole Moiety","volume":"144","year":"2013","journal-title":"Monatshefte Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1021\/ci100384d","article-title":"Chemical Name to Structure: OPSIN, an Open Source Solution","volume":"51","author":"Lowe","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open Babel: An Open Chemical Toolbox","volume":"3","author":"Banck","year":"2011","journal-title":"J. Cheminformatics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5079\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:40:54Z","timestamp":1760107254000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,7]]},"references-count":53,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105079"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105079","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,7]]}}}