{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:24:38Z","timestamp":1787505878569,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Ministry of Education and Science","award":["122112800079-7"],"award-info":[{"award-number":["122112800079-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Although the COVID-19 pandemic caused by SARS-CoV-2 viruses is officially over, the search for new effective agents with activity against a wide range of coronaviruses is still an important task for medical chemists and virologists. We synthesized a series of thiazolo-thiophenes based on (+)- and (\u2212)-usnic acid and studied their ability to inhibit the main protease of SARS-CoV-2. Substances containing unsubstituted thiophene groups or methyl- or bromo-substituted thiophene moieties showed moderate activity. Derivatives containing nitro substituents in the thiophene heterocycle\u2014just as pure (+)- and (\u2212)-usnic acids\u2014showed no anti-3CLpro activity. Kinetic parameters of the most active compound, (+)-3e, were investigated, and molecular modeling of the possible interaction of the new thiazolo-thiophenes with the active site of the main protease was carried out. We evaluated the binding energies of the ligand and protein in a ligand\u2013protein complex. Active compound (+)-3e was found to bind with minimum free energy; the binding of inactive compound (+)-3g is characterized by higher values of minimum free energy; the positioning of pure (+)-usnic acid proved to be unstable and is accompanied by the formation of intermolecular contacts with many amino acids of the catalytic binding site. Thus, the molecular dynamics results were consistent with the experimental data. In an in vitro antiviral assay against six strains (Wuhan, Delta, and four Omicron sublineages) of SARS-CoV-2, (+)-3e demonstrated pronounced antiviral activity against all the strains.<\/jats:p>","DOI":"10.3390\/v16020215","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T09:41:59Z","timestamp":1706694119000},"page":"215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Potential of Usnic-Acid-Based Thiazolo-Thiophenes as Inhibitors of the Main Protease of SARS-CoV-2 Viruses"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-4893","authenticated-orcid":false,"given":"Olga I.","family":"Yarovaya","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2798-2844","authenticated-orcid":false,"given":"Aleksandr S.","family":"Filimonov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1795-9256","authenticated-orcid":false,"given":"Dmitriy S.","family":"Baev","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"},{"name":"Synchrotron Radiation Facility SKIF, G.K. Boreskov Institute of Catalysis SB RAS, 630559 Koltsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8481-0470","authenticated-orcid":false,"given":"Sophia S.","family":"Borisevich","sequence":"additional","affiliation":[{"name":"Synchrotron Radiation Facility SKIF, G.K. Boreskov Institute of Catalysis SB RAS, 630559 Koltsovo, Russia"},{"name":"Laboratory of Chemical Physics, Ufa Institute of Chemistry, Ufa Federal Research Centre, 450078 Ufa, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna V.","family":"Zaykovskaya","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0492-154X","authenticated-orcid":false,"given":"Varvara Yu.","family":"Chirkova","sequence":"additional","affiliation":[{"name":"Institute of Biology and Biotechnology, Altay State University, 656049 Barnaul, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya K.","family":"Marenina","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5935-2540","authenticated-orcid":false,"given":"Yulia V.","family":"Meshkova","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-6335","authenticated-orcid":false,"given":"Svetlana V.","family":"Belenkaya","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"},{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-4453","authenticated-orcid":false,"given":"Dmitriy N.","family":"Shcherbakov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"},{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia"},{"name":"Institute of Biology and Biotechnology, Altay State University, 656049 Barnaul, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-922X","authenticated-orcid":false,"given":"Maxim A.","family":"Gureev","sequence":"additional","affiliation":[{"name":"Laboratory of Bio- and Cheminformatics, St. Petersburg School of Physics, Mathematics and Computer Science, HSE University, 194100 St. Peterburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8627-3453","authenticated-orcid":false,"given":"Olga A.","family":"Luzina","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg V.","family":"Pyankov","sequence":"additional","affiliation":[{"name":"State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, 630559 Koltsovo, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nariman F.","family":"Salakhutdinov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-4223","authenticated-orcid":false,"given":"Mikhail V.","family":"Khvostov","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1136\/bmj.p1041","article-title":"COVID-19: WHO Declares End of Global Health Emergency","volume":"368","author":"Wise","year":"2023","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sahoo, B.M., Ravi Kumar, B.V.V., Sruti, J., Mahapatra, M.K., Banik, B.K., and Borah, P. (2021). Drug Repurposing Strategy (DRS): Emerging Approach to Identify Potential Therapeutics for Treatment of Novel Coronavirus Infection. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.628144"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"116011","DOI":"10.1016\/j.ejmech.2023.116011","article-title":"Structure-Based Design of SARS-CoV-2 Papain-like Protease Inhibitors","volume":"264","author":"Jadhav","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.bbrc.2020.08.116","article-title":"RNA-Dependent RNA Polymerase: Structure, Mechanism, and Drug Discovery for COVID-19","volume":"538","author":"Jiang","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/jmv.25761","article-title":"The Potential Chemical Structure of Anti-SARS-CoV-2 RNA-dependent RNA Polymerase","volume":"92","author":"Lung","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100103","DOI":"10.1016\/j.metop.2021.100103","article-title":"Roles of Existing Drug and Drug Targets for COVID-19 Management","volume":"11","author":"Ayele","year":"2021","journal-title":"Metab. Open"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Narwal, M., Armache, J.-P., Edwards, T.J., and Murakami, K.S. (2023). SARS-CoV-2 Polyprotein Substrate Regulates the Stepwise Mpro Cleavage Reaction. J. Biol. Chem., 299.","DOI":"10.2210\/pdb8eir\/pdb"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12359","DOI":"10.1021\/acs.jmedchem.0c00606","article-title":"COVID-19: Drug Targets and Potential Treatments","volume":"63","author":"Gil","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1021\/jo901503d","article-title":"Enzyme Catalysis by Hydrogen Bonds: The Balance between Transition State Binding and Substrate Binding in Oxyanion Holes","volume":"75","author":"Goodman","year":"2010","journal-title":"J. Org. Chem."},{"key":"ref_11","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_12","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_13","first-page":"2118","article-title":"FDA Grants Full Approval to Paxlovid, COVID-19 Antiviral Treatment","volume":"329","author":"Harris","year":"2023","journal-title":"JAMA"},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1093\/jac\/dkad027","article-title":"Efficacy Comparison of 3CL Protease Inhibitors Ensitrelvir and Nirmatrelvir against SARS-CoV-2 in Vitro and in Vivo","volume":"78","author":"Kuroda","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115491","DOI":"10.1016\/j.ejmech.2023.115491","article-title":"European Journal of Medicinal Chemistry The Research Progress of SARS-CoV-2 Main Protease Inhibitors from 2020 to 2022","volume":"257","author":"Pang","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1070\/RCR4969","article-title":"Mono- and Sesquiterpenes as a Starting Platform for the Development of Antiviral Drugs","volume":"90","author":"Yarovaya","year":"2021","journal-title":"Russ. Chem. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.57634\/RCR5056","article-title":"Antiviral Properties of Diterpenes and Their Derivatives","volume":"92","author":"Yarovaya","year":"2023","journal-title":"Russ. Chem. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5384","DOI":"10.1002\/ptr.7151","article-title":"Natural Products and Phytochemicals as Potential Anti-SARS-CoV-2 Drugs","volume":"35","author":"Merarchi","year":"2021","journal-title":"Phyther. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4774","DOI":"10.1080\/07391102.2020.1780947","article-title":"Natural Compounds from Clerodendrum Spp. as Possible Therapeutic Candidates against SARS-CoV-2: An in Silico Investigation","volume":"39","author":"Kar","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yarovaya, O.I., Shcherbakov, D.N., Borisevich, S.S., Sokolova, A.S., Gureev, M.A., Khamitov, E.M., Rudometova, N.B., Zybkina, A.V., Mordvinova, E.D., and Zaykovskaya, A.V. (2022). Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses. Viruses, 14.","DOI":"10.3390\/v14061295"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Baev, D.S., Blokhin, M.E., Chirkova, V.Y., Belenkaya, S.V., Luzina, O.A., Yarovaya, O.I., Salakhutdinov, N.F., and Shcherbakov, D.N. (2022). Triterpenic Acid Amides as Potential Inhibitors of the SARS-CoV-2 Main Protease. Molecules, 28.","DOI":"10.3390\/molecules28010303"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fomenko, V.V., Rudometova, N.B., Yarovaya, O.I., Rogachev, A.D., Fando, A.A., Zaykovskaya, A.V., Komarova, N.I., Shcherbakov, D.N., Pyankov, O.V., and Pokrovsky, A.G. (2022). Synthesis and In Vitro Study of Antiviral Activity of Glycyrrhizin Nicotinate Derivatives against HIV-1 Pseudoviruses and SARS-CoV-2 Viruses. Molecules, 27.","DOI":"10.3390\/molecules27010295"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Filimonov, A.S., Yarovaya, O.I., Zaykovskaya, A.V., Rudometova, N.B., Shcherbakov, D.N., Chirkova, V.Y., Baev, D.S., Borisevich, S.S., Luzina, O.A., and Pyankov, O.V. (2022). (+)-Usnic Acid and Its Derivatives as Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses. Viruses, 14.","DOI":"10.3390\/v14102154"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19865","DOI":"10.1039\/D3NJ03598K","article-title":"Usnic Acid Based Thiazole-Hydrazones as Multi-Targeting Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses","volume":"47","author":"Yarovaya","year":"2023","journal-title":"New J. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pathania, S., and Chawla, P.A. (2020). Thiophene-Based Derivatives as Anticancer Agents: An Overview on Decade\u2019s Work. Bioorg. Chem., 101.","DOI":"10.1016\/j.bioorg.2020.104026"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2100462","DOI":"10.1002\/ardp.202100462","article-title":"Thiophene-containing Compounds with Antimicrobial Activity","volume":"355","author":"Roman","year":"2022","journal-title":"Arch. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Qandeel, N.A., El-Damasy, A.K., Sharawy, M.H., Bayomi, S.M., and El-Gohary, N.S. (2020). Synthesis, in Vivo Anti-Inflammatory, COX-1\/COX-2 and 5-LOX Inhibitory Activities of New 2,3,4-Trisubstituted Thiophene Derivatives. Bioorg. Chem., 102.","DOI":"10.1016\/j.bioorg.2020.103890"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.biomag.2014.08.002","article-title":"Synthesis, in Silico Preclinical Evaluation, Antidepressant Potential of 5-Substituted Phenyl-3-(Thiophen-2-Yl)-4,5-Dihydro-1h-Pyrazole-1-Carboxamides","volume":"4","author":"Mathew","year":"2014","journal-title":"Biomed. Aging Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ejmech.2012.12.003","article-title":"Synthesis and Biological Evaluation of Thieno [2\u2032,3\u2032:4,5]Pyrimido [1,2-b][1,2,4]Triazines and Thieno [2,3-d][1,2,4]Triazolo [1,5-a]Pyrimidines as Anti-Inflammatory and Analgesic Agents","volume":"62","author":"Ashour","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4376","DOI":"10.1016\/j.ejmech.2009.05.026","article-title":"A New Class of Anticonvulsants Possessing 6Hz Activity: 3,4-Dialkyloxy Thiophene Bishydrazones","volume":"44","author":"Kulandasamy","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1021\/tx500134g","article-title":"Bioactivation Potential of Thiophene-Containing Drugs","volume":"27","author":"Gramec","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1800225","DOI":"10.1002\/ardp.201800225","article-title":"Synthesis of Novel Derivatives of 7,8-dihydro-6H-imidazo [2,1-b][1,3]Benzothiazol-5-one and Their Virus-inhibiting Activity against Influenza A Virus","volume":"352","author":"Galochkina","year":"2019","journal-title":"Arch. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gharbi-Ayachi, A., Santhanakrishnan, S., Wong, Y.H., Chan, K.W.K., Tan, S.T., Bates, R.W., Vasudevan, S.G., El Sahili, A., and Lescar, J. (2020). Non-Nucleoside Inhibitors of Zika Virus RNA-Dependent RNA Polymerase. J. Virol., 94.","DOI":"10.1128\/JVI.00794-20"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105418","DOI":"10.1016\/j.antiviral.2022.105418","article-title":"Anti-Influenza Virus Activity of the REV-ERB\u03b1 Agonist SR9009 and Related Analogues","volume":"207","author":"Cheng","year":"2022","journal-title":"Antiviral Res."},{"key":"ref_36","unstructured":"Polovinka, M.P., Salakhutdinov, N.F., and Panchenko, M.Y. (2006). Method for Preparing Usnic Acid. (RU2317076), Patent."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Filimonov, A.S., Chepanova, A.A., Luzina, O.A., Zakharenko, A.L., Zakharova, O.D., Ilina, E.S., Dyrkheeva, N.S., Kuprushkin, M.S., Kolotaev, A.V., and Khachatryan, D.S. (2019). New Hydrazinothiazole Derivatives of Usnic Acid as Potent Tdp1 Inhibitors. Molecules, 24.","DOI":"10.3390\/molecules24203711"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Belenkaya, S.V., Merkuleva, I.A., Yarovaya, O.I., Chirkova, V.Y., Sharlaeva, E.A., Shanshin, D.V., Volosnikova, E.A., Vatsadze, S.Z., Khvostov, M.V., and Salakhutdinov, N.F. (2023). The Main Protease 3CLpro of the SARS-CoV-2 Virus: How to Turn an Enemy into a Helper. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1294266"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_40","unstructured":"(2022). Schrodinger Realease 2022-1: Small Molecule Drug Discovery Suite, Schr\u00f6dinger, LLC."},{"key":"ref_41","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."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lockbaum, G.J., Reyes, A.C., Lee, J.M., Tilvawala, R., Nalivaika, E.A., Ali, A., Kurt Yilmaz, N., Thompson, P.R., and Schiffer, C.A. (2021). Crystal Structure of SARS-CoV-2 Main Protease in Complex with the Non-Covalent Inhibitor ML188. Viruses, 13.","DOI":"10.2210\/pdb7l0d\/pdb"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1021\/acs.jctc.1c00302","article-title":"OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space","volume":"17","author":"Lu","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Suenaga, A., Okimoto, N., Hirano, Y., and Fukui, K. (2012). An Efficient Computational Method for Calculating Ligand Binding Affinities. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042846"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s11101-020-09717-1","article-title":"Usnic Acid: From an Ancient Lichen Derivative to Promising Biological and Nanotechnology Applications","volume":"20","author":"Macedo","year":"2021","journal-title":"Phytochem. Rev."},{"key":"ref_46","unstructured":"(2023, November 18). Available online: https:\/\/www.plantarium.ru\/lang\/en\/page\/view\/item\/75054.html."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13118","DOI":"10.1038\/s41598-022-17506-3","article-title":"(+)-Usnic Acid and Its Salts, Inhibitors of SARS-CoV-2, Identified by Using in Silico Methods and in Vitro Assay","volume":"12","author":"Oh","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6386","DOI":"10.1007\/s12010-022-04103-3","article-title":"Exploration of Novel Lichen Compounds as Inhibitors of SARS-CoV-2 Mpro: Ligand-Based Design, Molecular Dynamics, and ADMET Analyses","volume":"194","author":"Gupta","year":"2022","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Roney, M., Singh, G., Huq, A.K.M.M., Forid, M.S., Ishak, W.M.B.W., Rullah, K., Aluwi, M.F.F.M., and Tajuddin, S.N. (2023). Identification of Pyrazole Derivatives of Usnic Acid as Novel Inhibitor of SARS-CoV-2 Main Protease Through Virtual Screening Approaches. Mol. Biotechnol.","DOI":"10.1007\/s12033-023-00667-5"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1021\/acsptsci.0c00130","article-title":"Ebselen, Disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin Are Nonspecific Promiscuous SARS-CoV-2 Main Protease Inhibitors","volume":"3","author":"Ma","year":"2020","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/med.21862","article-title":"Haste Makes Waste: A Critical Review of Docking-based Virtual Screening in Drug Repurposing for SARS-CoV-2 Main Protease (M-pro) Inhibition","volume":"42","author":"Macip","year":"2022","journal-title":"Med. Res. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Manelfi, C., Gossen, J., Gervasoni, S., Talarico, C., Albani, S., Philipp, B.J., Musiani, F., Vistoli, G., Rossetti, G., and Beccari, A.R. (2021). Combining Different Docking Engines and Consensus Strategies to Design and Validate Optimized Virtual Screening Protocols for the SARS-CoV-2 3CL Protease. Molecules, 26.","DOI":"10.3390\/molecules26040797"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5196","DOI":"10.1038\/s41467-022-32854-4","article-title":"X-ray Crystallographic Characterization of the SARS-CoV-2 Main Protease Polyprotein Cleavage Sites Essential for Viral Processing and Maturation","volume":"13","author":"Lee","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/JVI.01357-21","article-title":"Natural and Recombinant SARS-CoV-2 Isolates Rapidly Evolve In Vitro to Higher Infectivity through More Efficient Binding to Heparan Sulfate and Reduced S1\/S2 Cleavage","volume":"95","author":"Shiliaev","year":"2021","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s12223-022-01001-3","article-title":"Delta Variant (B.1.617.2) of SARS-CoV-2: Current Understanding of Infection, Transmission, Immune Escape, and Mutational Landscape","volume":"68","author":"Bhattacharya","year":"2023","journal-title":"Folia Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/med.21941","article-title":"Research Progress in Spike Mutations of SARS-CoV-2 Variants and Vaccine Development","volume":"43","author":"He","year":"2023","journal-title":"Med. Res. Rev."},{"key":"ref_57","first-page":"2017","article-title":"Human Airway and Nasal Organoids Reveal Escalating Replicative Fitness of SARS-CoV-2 Emerging Variants","volume":"120","author":"Li","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1038\/s41591-022-01911-2","article-title":"Emergence of SARS-CoV-2 Omicron Lineages BA.4 and BA.5 in South Africa","volume":"28","author":"Tegally","year":"2022","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jobb.2023.01.002","article-title":"Evolutionary Analysis of Omicron Variant BF.7 and BA.5.2 Pandemic in China","volume":"5","author":"Sun","year":"2023","journal-title":"J. Biosaf. Biosecurity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e239","DOI":"10.1002\/mco2.239","article-title":"The Rapid Rise of SARS-CoV-2 Omicron Subvariants with Immune Evasion Properties: XBB.1.5 and BQ.1.1 Subvariants","volume":"4","author":"Ao","year":"2023","journal-title":"MedComm"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.cell.2022.12.018","article-title":"Alarming Antibody Evasion Properties of Rising SARS-CoV-2 BQ and XBB Subvariants","volume":"186","author":"Wang","year":"2023","journal-title":"Cell"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/2\/215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:52:21Z","timestamp":1760104341000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/2\/215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,31]]},"references-count":61,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["v16020215"],"URL":"https:\/\/doi.org\/10.3390\/v16020215","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,31]]}}}