{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:55:09Z","timestamp":1792637709624,"version":"4.5.0"},"reference-count":124,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:00:00Z","timestamp":1693612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FFABR_PA_MICALE_NICOLA_ATENEO_2022"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.<\/jats:p>","DOI":"10.3390\/biom13091339","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:14:50Z","timestamp":1693793690000},"page":"1339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5881-7142","authenticated-orcid":false,"given":"Andrea","family":"Citarella","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Milan, Via Golgi 19, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Dimasi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Milan, Via Golgi 19, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-9351","authenticated-orcid":false,"given":"Davide","family":"Moi","sequence":"additional","affiliation":[{"name":"Department of Chemical and Geological Sciences, University of Cagliari, S.P. 8 CA, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6180-9581","authenticated-orcid":false,"given":"Daniele","family":"Passarella","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Milan, Via Golgi 19, 20133 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2171-9033","authenticated-orcid":false,"given":"Angela","family":"Scala","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6004-5196","authenticated-orcid":false,"given":"Anna","family":"Piperno","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9294-6033","authenticated-orcid":false,"given":"Nicola","family":"Micale","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41573-023-00692-8","article-title":"Accelerating Antiviral Drug Discovery: Lessons from COVID-19","volume":"22","author":"Hall","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Citarella, A., Scala, A., Piperno, A., and Micale, N. (2021). SARS-CoV-2 Mpro: A Potential Target for Peptidomimetics and Small-Molecule Inhibitors. Biomolecules, 11.","DOI":"10.3390\/biom11040607"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"n2713","DOI":"10.1136\/bmj.n2713","article-title":"COVID-19: Pfizer\u2019s Paxlovid Is 89% Effective in Patients at Risk of Serious Illness, Company Reports","volume":"375","author":"Mahase","year":"2021","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e202100576","DOI":"10.1002\/cmdc.202100576","article-title":"A Patent Review on SARS Coronavirus Main Protease (3CL pro) Inhibitors","volume":"17","author":"Chia","year":"2022","journal-title":"ChemMedChem"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1080\/13543776.2021.1857726","article-title":"Protease Inhibitors Targeting the Main Protease and Papain-like Protease of Coronaviruses","volume":"31","author":"Capasso","year":"2021","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1111\/febs.12936","article-title":"From SARS to MERS: Crystallographic Studies on Coronaviral Proteases Enable Antiviral Drug Design","volume":"281","author":"Hilgenfeld","year":"2014","journal-title":"FEBS J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"393","DOI":"10.4155\/fmc-2021-0269","article-title":"Design of SARS-CoV-2 Mpro, PLpro Dual-Target Inhibitors Based on Deep Reinforcement Learning and Virtual Screening","volume":"14","author":"Zhang","year":"2022","journal-title":"Future Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1021\/acscombsci.0c00058","article-title":"Targeting the Dimerization of the Main Protease of Coronaviruses: A Potential Broad-Spectrum Therapeutic Strategy","volume":"22","author":"Goyal","year":"2020","journal-title":"ACS Comb. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"112711","DOI":"10.1016\/j.ejmech.2020.112711","article-title":"The Development of Coronavirus 3C-Like Protease (3CLpro) Inhibitors from 2010 to 2020","volume":"206","author":"Liu","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-020-2223-y","article-title":"Structure of Mpro from SARS-CoV-2 and Discovery of Its Inhibitors","volume":"582","author":"Jin","year":"2020","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e151","DOI":"10.1002\/mco2.151","article-title":"The SARS-CoV-2 Main Protease (M pro): Structure, Function, and Emerging Therapies for COVID-19","volume":"3","author":"Hu","year":"2022","journal-title":"MedComm"},{"key":"ref_12","unstructured":"(2023, February 28). RCSB PDB\u20147ALH: Crystal Structure of the Main Protease (3CLpro\/Mpro) of SARS-CoV-2 at 1.65A Resolution (Spacegroup C2). Available online: https:\/\/www.rcsb.org\/structure\/7ALH."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.abb3405","article-title":"Crystal Structure of SARS-CoV-2 Main Protease Provides a Basis for Design of Improved \u03b1-Ketoamide Inhibitors","volume":"368","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"ref_14","unstructured":"(2023, February 28). RCSB PDB\u20141P9S: Coronavirus Main Proteinase (3CLpro) Structure: Basis for Design of Anti-SARS Drugs. Available online: https:\/\/www.rcsb.org\/structure\/1P9S."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17365","DOI":"10.1074\/jbc.AC120.016154","article-title":"Unusual Zwitterionic Catalytic Site of SARS-CoV-2 Main Protease Revealed by Neutron Crystallography","volume":"295","author":"Kneller","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101972","DOI":"10.1016\/j.jbc.2022.101972","article-title":"Structural Basis for the in Vitro Efficacy of Nirmatrelvir against SARS-CoV-2 Variants","volume":"298","author":"Greasley","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12500","DOI":"10.1021\/acs.jmedchem.2c01005","article-title":"Targeting SARS-CoV-2 Main Protease for Treatment of COVID-19: Covalent Inhibitors Structure\u2013Activity Relationship Insights and Evolution Perspectives","volume":"65","author":"Bono","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1021\/acsinfecdis.0c00815","article-title":"Challenges for Targeting SARS-CoV-2 Proteases as a Therapeutic Strategy for COVID-19","volume":"7","author":"Steuten","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mangiavacchi, F., Botwina, P., Menichetti, E., Bagnoli, L., Rosati, O., Marini, F., Fonseca, S.F., Abenante, L., Alves, D., and Dabrowska, A. (2021). Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of Mpro and Its Antiviral Activity in Cells against SARS-CoV-2. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137048"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.cbpa.2008.03.009","article-title":"Peptidomimetics, a Synthetic Tool of Drug Discovery","volume":"12","author":"Vagner","year":"2008","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6595","DOI":"10.1021\/acs.jmedchem.5b01461","article-title":"An Overview of Severe Acute Respiratory Syndrome\u2013Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy","volume":"59","author":"Pillaiyar","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bz\u00f3wka, M., Mitusi\u0144ska, K., Raczy\u0144ska, A., Samol, A., Tuszy\u0144ski, J.A., and G\u00f3ra, A. (2020). Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design. Int. J. Mol. Sci., 21.","DOI":"10.1101\/2020.02.27.968008"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115667","DOI":"10.1016\/j.ejmech.2023.115667","article-title":"Exploring Diverse Reactive Warheads for the Design of SARS-CoV-2 Main Protease Inhibitors","volume":"259","author":"Tan","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ren, P., Li, H., Nie, T., Jian, X., Yu, C., Li, J., Su, H., Zhang, X., Li, S., and Yang, X. (J. Med. Chem., 2023). Discovery and Mechanism Study of SARS-CoV-2 3C-like Protease Inhibitors with a New Reactive Group, J. Med. Chem., Accepted Manuscript.","DOI":"10.1021\/acs.jmedchem.3c00818"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3390\/futurepharmacol3010006","article-title":"SARS-CoV-2 Mpro Inhibitors: Achieved Diversity, Developing Resistance and Future Strategies","volume":"3","author":"Fischer","year":"2023","journal-title":"Future Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2012.10.053","article-title":"Design, Synthesis and Crystallographic Analysis of Nitrile-Based Broad-Spectrum Peptidomimetic Inhibitors for Coronavirus 3C-like Proteases","volume":"59","author":"Chuck","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1021\/acscentsci.2c00369","article-title":"The Path to Paxlovid","volume":"8","author":"Halford","year":"2022","journal-title":"ACS Cent. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1126\/science.abl4784","article-title":"An Oral SARS-CoV-2 M pro Inhibitor Clinical Candidate for the Treatment of COVID-19","volume":"374","author":"Owen","year":"2021","journal-title":"Science"},{"key":"ref_29","unstructured":"(2023, March 05). Palace Welcomes FDA Approval of COVID Generic Drug|Inquirer News. Available online: https:\/\/newsinfo.inquirer.net\/1539269\/palace-welcomes-fda-ok-of-covid-generic-drug."},{"key":"ref_30","unstructured":"(2023, March 05). EMA Receives Application for Conditional Marketing Authorisation for Paxlovid (PF-07321332 and Ritonavir) for Treating Patients with COVID-19|European Medicines Agency. Available online: https:\/\/www.ema.europa.eu\/en\/news\/ema-receives-application-conditional-marketing-authorisation-paxlovid-pf-07321332-ritonavir-treating."},{"key":"ref_31","unstructured":"(2023, March 05). Oral COVID-19 Antiviral, Paxlovid, Approved by UK Regulator\u2014GOV.UK, Available online: https:\/\/www.gov.uk\/government\/news\/oral-covid-19-antiviral-paxlovid-approved-by-uk-regulator."},{"key":"ref_32","unstructured":"(2023, March 05). WO2021250648A1\u2014Nitrile-Containing Antiviral Compounds\u2014Google Patents. Available online: https:\/\/patents.google.com\/patent\/WO2021250648A1\/en."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1039\/D1MD00247C","article-title":"Peptidomimetic Nitrile Warheads as SARS-CoV-2 3CL Protease Inhibitors","volume":"12","author":"Bai","year":"2021","journal-title":"RSC Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"117316","DOI":"10.1016\/j.bmc.2023.117316","article-title":"Design, Synthesis and Biological Evaluation of Covalent Peptidomimetic 3CL Protease Inhibitors Containing Nitrile Moiety","volume":"87","author":"Zhu","year":"2023","journal-title":"Bioorg. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1038\/s41467-022-29915-z","article-title":"Covalent Narlaprevir- and Boceprevir-Derived Hybrid Inhibitors of SARS-CoV-2 Main Protease","volume":"13","author":"Kneller","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1021\/acs.jmedchem.2c01627","article-title":"Alkyne Derivatives of SARS-CoV-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit by Reacting Covalently with the Nucleophilic Cysteine","volume":"66","author":"Brewitz","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ngo, C., Fried, W., Aliyari, S., Feng, J., Qin, C., Zhang, S., Yang, H., Shanaa, J., Feng, P., and Cheng, G. (J. Med. Chem., 2023). Alkyne as a Latent Warhead to Covalently Target SARS-CoV-2 Main Protease, J. Med. Chem., Accepted Manuscript.","DOI":"10.1021\/acs.jmedchem.3c00810"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"13190","DOI":"10.1073\/pnas.1835675100","article-title":"The Crystal Structures of Severe Acute Respiratory Syndrome Virus Main Protease and Its Complex with an Inhibitor","volume":"100","author":"Yang","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1126\/science.abb4489","article-title":"Structure-Based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease","volume":"368","author":"Dai","year":"2020","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1021\/acs.jmedchem.0c02258","article-title":"Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2","volume":"65","author":"Dai","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1038\/s41467-020-18096-2","article-title":"Feline Coronavirus Drug Inhibits the Main Protease of SARS-CoV-2 and Blocks Virus Replication","volume":"11","author":"Vuong","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113584","DOI":"10.1016\/j.ejmech.2021.113584","article-title":"Improved SARS-CoV-2 Mpro Inhibitors Based on Feline Antiviral Drug GC376: Structural Enhancements, Increased Solubility, and Micellar Studies","volume":"222","author":"Vuong","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eabe0751","DOI":"10.1126\/sciadv.abe0751","article-title":"Structure and Inhibition of the SARS-CoV-2 Main Protease Reveal Strategy for Developing Dual Inhibitors against M pro and Cathepsin L","volume":"6","author":"Sacco","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1038\/s41467-022-29413-2","article-title":"Development of Optimized Drug-like Small Molecule Inhibitors of the SARS-CoV-2 3CL Protease for Treatment of COVID-19","volume":"13","author":"Liu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1126\/science.abf1611","article-title":"SARS-CoV-2 M pro Inhibitors with Antiviral Activity in a Transgenic Mouse Model","volume":"371","author":"Qiao","year":"2021","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"10047","DOI":"10.1021\/acs.jmedchem.1c00319","article-title":"Structure-Guided Design of Conformationally Constrained Cyclohexane Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3CL Protease","volume":"64","author":"Dampalla","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1021\/acsptsci.1c00099","article-title":"Rational Design of Hybrid SARS-CoV-2 Main Protease Inhibitors Guided by the Superimposed Cocrystal Structures with the Peptidomimetic Inhibitors GC-376, Telaprevir, and Boceprevir","volume":"4","author":"Xia","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11040","DOI":"10.1021\/acs.jmedchem.3c00221","article-title":"A Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease","volume":"66","author":"Geng","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"114596","DOI":"10.1016\/j.ejmech.2022.114596","article-title":"A Systematic Exploration of Boceprevir-Based Main Protease Inhibitors as SARS-CoV-2 Antivirals","volume":"240","author":"Alugubelli","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1126\/science.abf7945","article-title":"X-Ray Screening Identifies Active Site and Allosteric Inhibitors of SARS-CoV-2 Main Protease","volume":"372","author":"Reinke","year":"2021","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1021\/acsinfecdis.0c00761","article-title":"Boceprevir, Calpain Inhibitors II and XII, and GC-376 Have Broad-Spectrum Antiviral Activity against Coronaviruses","volume":"7","author":"Hu","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/cmdc.202000924","article-title":"A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors**","volume":"16","author":"Yang","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Costanzi, E., Kuzikov, M., Esposito, F., Albani, S., Demitri, N., Giabbai, B., Camasta, M., Tramontano, E., Rossetti, G., and Zaliani, A. (2021). Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro\/3CLpro) and Human Cathepsin-L. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111779"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"114570","DOI":"10.1016\/j.ejmech.2022.114570","article-title":"A Multi-Pronged Evaluation of Aldehyde-Based Tripeptidyl Main Protease Inhibitors as SARS-CoV-2 Antivirals","volume":"240","author":"Ma","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1007\/s00044-021-02832-4","article-title":"Isatin Derivatives as Broad-Spectrum Antiviral Agents: The Current Landscape","volume":"31","author":"Elsaman","year":"2022","journal-title":"Med. Chem. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Jiang, X., Li, J., Viayna, A., Luque, F.J., Woodson, M., Jing, L., Gao, S., Zhao, F., Xie, M., and Toth, K. (RSC Med. Chem., 2023). Identification of Novel 1,2,3-Triazole Isatin Derivatives as Potent SARS-CoV-2 3CLpro Inhibitors via Click-Chemistry-Based Rapid Screening, RSC Med. Chem., Accepted Manuscript.","DOI":"10.1039\/D3MD00306J"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"12725","DOI":"10.1021\/acs.jmedchem.0c01063","article-title":"Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19","volume":"63","author":"Hoffman","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1021\/acs.jmedchem.1c00616","article-title":"Peptidomimetic \u03b1-Acyloxymethylketone Warheads with Six-Membered Lactam P1 Glutamine Mimic: SARS-CoV-2 3CL Protease Inhibition, Coronavirus Antiviral Activity, and in Vitro Biological Stability","volume":"65","author":"Bai","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1021\/bi00233a007","article-title":"Peptidyl (Acyloxy)Methyl Ketones and the Quiescent Affinity Label Concept: The Departing Group as a Variable Structural Element in the Design of Inactivators of Cysteine Proteinases","volume":"30","author":"Krantz","year":"1991","journal-title":"Biochemistry"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Hu, X., Lin, C., Xu, Q., Zhou, X., Zeng, P., McCormick, P.J., Jiang, H., Li, J., and Zhang, J. (2022). Structural Basis for the Inhibition of Coronaviral Main Proteases by a Benzothiazole-Based Inhibitor. Viruses, 14.","DOI":"10.3390\/v14092075"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.ejmech.2013.07.037","article-title":"Development of Potent Dipeptide-Type SARS-CoV 3CL Protease Inhibitors with Novel P3 Scaffolds: Design, Synthesis, Biological Evaluation, and Docking Studies","volume":"68","author":"Thanigaimalai","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1038\/s41467-023-36729-0","article-title":"Identification of SARS-CoV-2 Mpro Inhibitors Containing P1\u2032 4-Fluorobenzothiazole Moiety Highly Active against SARS-CoV-2","volume":"14","author":"Tsuji","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"115512","DOI":"10.1016\/j.ejmech.2023.115512","article-title":"Design, Synthesis and Biological Evaluation of Peptidomimetic Benzothiazolyl Ketones as 3CLpro Inhibitors against SARS-CoV-2","volume":"257","author":"Yang","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Citarella, A., and Micale, N. (2020). Peptidyl Fluoromethyl Ketones and Their Applications in Medicinal Chemistry. Molecules, 25.","DOI":"10.3390\/molecules25174031"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1021\/acsptsci.0c00108","article-title":"Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening","volume":"3","author":"Zhu","year":"2020","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4652","DOI":"10.1016\/j.bmc.2008.02.040","article-title":"Design, Synthesis, and Evaluation of Trifluoromethyl Ketones as Inhibitors of SARS-CoV 3CL Protease","volume":"16","author":"Shao","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Citarella, A., Gentile, D., Rescifina, A., Piperno, A., Mognetti, B., Gribaudo, G., Sciortino, M.T., Holzer, W., Pace, V., and Micale, N. (2021). Pseudo-Dipeptide Bearing \u03b1,\u03b1-Difluoromethyl Ketone Moiety as Electrophilic Warhead with Activity against Coronaviruses. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031398"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8293","DOI":"10.1039\/D2OB01382G","article-title":"Synthesis, Computational Investigation and Biological Evaluation of \u03b1,\u03b1-Difluoromethyl Ketones Embodying Pyrazole and Isoxazole Nuclei as COX Inhibitors","volume":"20","author":"Citarella","year":"2022","journal-title":"Org. Biomol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8261","DOI":"10.1021\/acs.orglett.9b03024","article-title":"Direct and Chemoselective Synthesis of Tertiary Difluoroketones via Weinreb Amide Homologation with a CHF 2-Carbene Equivalent","volume":"21","author":"Miele","year":"2019","journal-title":"Org. Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1021\/acsmedchemlett.1c00299","article-title":"Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors","volume":"13","author":"Shcherbakov","year":"2022","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"114046","DOI":"10.1016\/j.ejmech.2021.114046","article-title":"Design, Synthesis and in Vitro Evaluation of Novel SARS-CoV-2 3CLpro Covalent Inhibitors","volume":"229","author":"Stille","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"20697","DOI":"10.1021\/jacs.1c08060","article-title":"Discovery of Di- and Trihaloacetamides as Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity","volume":"143","author":"Ma","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1039\/D1SC06596C","article-title":"Selective Covalent Targeting of SARS-CoV-2 Main Protease by Enantiopure Chlorofluoroacetamide","volume":"13","author":"Yamane","year":"2022","journal-title":"Chem. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/s41589-018-0204-3","article-title":"Selective and Reversible Modification of Kinase Cysteines with Chlorofluoroacetamides","volume":"15","author":"Shindo","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"114130","DOI":"10.1016\/j.ejmech.2022.114130","article-title":"In Silico Screening-Based Discovery of Novel Covalent Inhibitors of the SARS-CoV-2 3CL Protease","volume":"231","author":"Xiong","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1021\/acs.jcim.1c00851","article-title":"High-Throughput Virtual Screening and Validation of a SARS-CoV-2 Main Protease Noncovalent Inhibitor","volume":"62","author":"Clyde","year":"2022","journal-title":"J. Chem. Inf. Model"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"13343","DOI":"10.1021\/acs.jmedchem.2c01146","article-title":"Discovery and Crystallographic Studies of Trisubstituted Piperazine Derivatives as Non-Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity and Low Toxicity","volume":"65","author":"Gao","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"16902","DOI":"10.1021\/acs.jmedchem.2c01716","article-title":"Discovery and Crystallographic Studies of Nonpeptidic Piperazine Derivatives as Covalent SARS-CoV-2 Main Protease Inhibitors","volume":"65","author":"Gao","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Moon, P., Boike, L., Dovala, D., Henning, N.J., Knapp, M., Spradlin, J.N., Ward, C.C., Wolleb, H., Zammit, C.M., and Fuller, D. (2022). Discovery of Potent Pyrazoline-Based Covalent SARS-CoV-2 Main Protease Inhibitors. bioRxiv.","DOI":"10.1101\/2022.03.05.483025"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.1039\/D1SC05892D","article-title":"Computationally Driven Discovery of SARS-CoV-2 M pro Inhibitors: From Design to Experimental Validation","volume":"13","author":"Jing","year":"2022","journal-title":"Chem. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4562","DOI":"10.1021\/acs.jmedchem.9b01828","article-title":"\u03b1-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment","volume":"63","author":"Zhang","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1021\/acs.chemrev.5b00443","article-title":"Recent developments in general methodologies for the synthesis of \u03b1-ketoamides","volume":"116","author":"Pollini","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"13328","DOI":"10.1021\/acs.jmedchem.2c01131","article-title":"Diastereomeric Resolution Yields Highly Potent Inhibitor of SARS-CoV-2 Main Protease","volume":"65","author":"Cooper","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/s41564-022-01119-7","article-title":"An Orally Available Mpro Inhibitor Is Effective against Wild-Type SARS-CoV-2 and Variants Including Omicron","volume":"7","author":"Quan","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chen, X., Huang, X., Ma, Q., Kuzmi\u010d, P., Zhou, B., Xu, J., Liu, B., Jiang, H., Zhang, W., and Yang, C. (2023). Inhibition Mechanism and Antiviral Activity of an \u03b1-Ketoamide Based SARS-CoV-2 Main Protease Inhibitor. bioRxiv.","DOI":"10.21203\/rs.3.rs-2634509\/v1"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41392-023-01392-w","article-title":"A New Generation Mpro Inhibitor with Potent Activity against SARS-CoV-2 Omicron Variants","volume":"8","author":"Huang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"107575","DOI":"10.1016\/j.jsb.2020.107575","article-title":"SARS-CoV and SARS-CoV-2 main protease residue interaction networks change when bound to inhibitor N3","volume":"211","author":"Griffin","year":"2020","journal-title":"J. Struct. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1038\/s41467-021-22362-2","article-title":"Lead Compounds for the Development of SARS-CoV-2 3CL Protease Inhibitors","volume":"12","author":"Iketani","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1021\/acs.jcim.1c00184","article-title":"Lead Discovery of SARS-CoV-2 Main Protease Inhibitors through Covalent Docking-Based Virtual Screening","volume":"61","author":"Amendola","year":"2021","journal-title":"J. Chem. Inf. Model"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"115021","DOI":"10.1016\/j.ejmech.2022.115021","article-title":"Structure-Based Lead Optimization of Peptide-Based Vinyl Methyl Ketones as SARS-CoV-2 Main Protease Inhibitors","volume":"247","author":"Previti","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"21035","DOI":"10.1021\/jacs.2c04626","article-title":"Dual Inhibitors of Main Protease (M Pro) and Cathepsin L as Potent Antivirals against SARS-CoV2","volume":"144","author":"Mondal","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1039\/D3OB00381G","article-title":"Synthesis of SARS-CoV-2 Mpro Inhibitors Bearing a Cinnamic Ester Warhead with in Vitro Activity against Human Coronaviruses","volume":"21","author":"Citarella","year":"2023","journal-title":"Org. Biomol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/j.chembiol.2021.05.018","article-title":"An Automatic Pipeline for the Design of Irreversible Derivatives Identifies a Potent SARS-CoV-2 M pro Inhibitor","volume":"28","author":"Zaidman","year":"2021","journal-title":"Cell Chem. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1021\/acsptsci.0c00216","article-title":"Identification of Inhibitors of SARS-CoV-2 3CL-Pro Enzymatic Activity Using a Small Molecule in Vitro Repurposing Screen","volume":"4","author":"Kuzikov","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1038\/s41467-021-23751-3","article-title":"Identification of Pyrogallol as a Warhead in Design of Covalent Inhibitors for the SARS-CoV-2 3CL Protease","volume":"12","author":"Su","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"14702","DOI":"10.1021\/acs.jmedchem.1c01214","article-title":"Indole Chloropyridinyl Ester-Derived SARS-CoV-2 3CLpro Inhibitors: Enzyme Inhibition, Antiviral Efficacy, Structure-Activity Relationship, and X-ray Structural Studies","volume":"64","author":"Ghosh","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e01833-20","DOI":"10.1128\/mBio.01833-20","article-title":"GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection","volume":"11","author":"Hattori","year":"2020","journal-title":"mBio"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41467-021-20900-6","article-title":"A Small Molecule Compound with an Indole Moiety Inhibits the Main Protease of SARS-CoV-2 and Blocks Virus Replication","volume":"12","author":"Hattori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"10423","DOI":"10.1002\/anie.202016961","article-title":"Targeting the Main Protease of SARS-CoV-2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors","volume":"60","author":"Breidenbach","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"9376","DOI":"10.1021\/acs.jmedchem.2c00636","article-title":"Small-Molecule Thioesters as SARS-CoV-2 Main Protease Inhibitors: Enzyme Inhibition, Structure\u2013Activity Relationships, Antiviral Activity, and X-Ray Structure Determination","volume":"65","author":"Pillaiyar","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1038\/s41467-021-23313-7","article-title":"Inhibition Mechanism of SARS-CoV-2 Main Protease by Ebselen and Its Derivatives","volume":"12","author":"Amporndanai","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Zmudzinski, M., Rut, W., Olech, K., Granda, J., Giurg, M., Burda-Grabowska, M., Zhang, L., Sun, X., Lv, Z., and Nayak, D. (2020). Ebselen Derivatives Are Very Potent Dual Inhibitors of SARS-CoV-2 Proteases\u2014PLpro and Mpro in in Vitro Studies. bioRxiv.","DOI":"10.1101\/2020.08.30.273979"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1021\/acs.jmedchem.1c00566","article-title":"Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors","volume":"65","author":"Huff","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"104889","DOI":"10.1016\/j.bioorg.2021.104889","article-title":"Ebsulfur and Ebselen as Highly Potent Scaffolds for the Development of Potential SARS-CoV-2 Antivirals","volume":"112","author":"Sun","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"128526","DOI":"10.1016\/j.bmcl.2022.128526","article-title":"Discovery of Highly Potent SARS-CoV-2 Mpro Inhibitors Based on Benzoisothiazolone Scaffold","volume":"58","author":"Chen","year":"2022","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Song, L., Gao, S., Ye, B., Yang, M., Cheng, Y., Kang, D., Yi, F., Sun, J.-P., Men\u00e9ndez-Arias, L., and Neyts, J. (Acta Pharm. Sin. B, 2023). Medicinal Chemistry Strategies towards the Development of Non-Covalent SARS-CoV-2 Mpro Inhibitors, Acta Pharm. Sin. B, in press.","DOI":"10.1016\/j.apsb.2023.08.004"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s10930-020-09884-2","article-title":"Covalent Versus Non-Covalent Enzyme Inhibition: Which Route Should We Take? A Justification of the Good and Bad from Molecular Modelling Perspective","volume":"39","author":"Aljoundi","year":"2020","journal-title":"Protein J."},{"key":"ref_108","first-page":"3168","article-title":"Broad-Spectrum Non-Covalent Coronavirus Protease Inhibitors","volume":"797","author":"John","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1021\/acs.jmedchem.1c00509","article-title":"Expedited Approach toward the Rational Design of Noncovalent SARS-CoV-2 Main Protease Inhibitors","volume":"65","author":"Kitamura","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1021\/acs.jmedchem.2c00117","article-title":"Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19","volume":"65","author":"Unoh","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3917","DOI":"10.1021\/acs.jcim.1c00355","article-title":"Structure-Based Discovery of Novel Nonpeptide Inhibitors Targeting SARS-CoV-2 M pro","volume":"61","author":"Yang","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1021\/acs.jmedchem.1c00598","article-title":"Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro)","volume":"65","author":"Han","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"128099","DOI":"10.1016\/j.bmcl.2021.128099","article-title":"Promising Anti-SARS-CoV-2 Drugs by Effective Dual Targeting against the Viral and Host Proteases","volume":"43","author":"Elseginy","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1021\/jacs.1c08402","article-title":"Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses","volume":"144","author":"Luttens","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1038\/s41598-022-06306-4","article-title":"Non-Covalent SARS-CoV-2 Mpro Inhibitors Developed from in Silico Screen Hits","volume":"12","author":"Rossetti","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"115487","DOI":"10.1016\/j.ejmech.2023.115487","article-title":"Discovery of Quinazolin-4-One-Based Non-Covalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 2 Main Protease (SARS-CoV-2 Mpro)","volume":"257","author":"Zhang","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Citarella, A., Moi, D., Pedrini, M., P\u00e9rez-Pe\u00f1a, H., Pieraccini, S., Stagno, C., Micale, N., Schirmeister, T., Sibille, G., and Gribaudo, G. (2023). Discovery of a Novel Trifluoromethyl Diazirine Inhibitor of SARS-CoV-2 Mpro. Molecules, 28.","DOI":"10.3390\/molecules28020514"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Ielo, L., Patamia, V., Citarella, A., Efferth, T., Shahhamzehei, N., Schirmeister, T., Stagno, C., Langer, T., Rescifina, A., and Micale, N. (2022). Novel Class of Proteasome Inhibitors: In Silico and In Vitro Evaluation of Diverse Chloro(Trifluoromethyl)Aziridines. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012363"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Alhadrami, H.A., Burgio, G., Thissera, B., Orfali, R., Jiffri, S.E., Yaseen, M., Sayed, A.M., and Rateb, M.E. (2022). Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors. Mar. Drugs, 20.","DOI":"10.3390\/md20030163"},{"key":"ref_120","first-page":"1253","article-title":"Structure-Based Discovery and Structural Basis of a Novel Broad-Spectrum Natural Product against the Main Protease of Coronavirus","volume":"96","author":"Zhang","year":"2022","journal-title":"J. Virol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.scib.2020.10.018","article-title":"Crystal Structure of SARS-CoV-2 Main Protease in Complex with the Natural Product Inhibitor Shikonin Illuminates a Unique Binding Mode","volume":"66","author":"Li","year":"2021","journal-title":"Sci. Bull."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"114030","DOI":"10.1016\/j.ejmech.2021.114030","article-title":"Discovery of 9,10-Dihydrophenanthrene Derivatives as SARS-CoV-2 3CLpro Inhibitors for Treating COVID-19","volume":"228","author":"Zhang","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"105381","DOI":"10.1016\/j.antiviral.2022.105381","article-title":"Allosteric Inhibitors of the Main Protease of SARS-CoV-2","volume":"205","author":"Samrat","year":"2022","journal-title":"Antiviral. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"mjac039","DOI":"10.1093\/jmcb\/mjac039","article-title":"Apixaban, an Orally Available Anticoagulant, Inhibits SARS-CoV-2 Replication and Its Major Protease in a Non-Competitive Way","volume":"14","author":"Chaves","year":"2022","journal-title":"J. Mol. Cell Biol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/9\/1339\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:45:26Z","timestamp":1760129126000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/9\/1339"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,2]]},"references-count":124,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["biom13091339"],"URL":"https:\/\/doi.org\/10.3390\/biom13091339","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,2]]}}}