{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:18:33Z","timestamp":1790957913750,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The thioureido derivative 3 was formed when compound 2 was treated with sulfamerazine. Also, compound 3 was reacted with NH2-NH2 in ethanol to produce the N-aminoquinazoline derivative. Additionally, derivative 4 was reacted with 4-hydroxy-3-methoxybenzaldehyde, ethyl chloroacetate, and\/or diethyl oxalate to produce quinazoline derivatives 5, 6, and 12, respectively. The results of the pharmacological study indicated that the synthesized 4\u20136 and 12 derivatives showed good 3CLpro, cPLA2, and sPLA2 inhibitory activity. The IC50 values of the target compounds 4\u20136, and 12 against the SARS-CoV-2 main protease were 2.012, 3.68, 1.18, and 5.47 \u00b5M, respectively, whereas those of baicalein and ivermectin were 1.72 and 42.39 \u00b5M, respectively. The IC50 values of the target compounds 4\u20136, and 12 against sPLA2 were 2.84, 2.73, 1.016, and 4.45 \u00b5M, respectively, whereas those of baicalein and ivermectin were 0.89 and 109.6 \u00b5M, respectively. The IC50 values of the target compounds 4\u20136, and 12 against cPLA2 were 1.44, 2.08, 0.5, and 2.39 \u00b5M, respectively, whereas those of baicalein and ivermectin were 3.88 and 138.0 \u00b5M, respectively. Also, incubation of lung cells with LPS plus derivatives 4\u20136, and 12 caused a significant decrease in levels of sPLA2, cPLA2, IL-8, TNF-\u03b1, and NO. The inhibitory activity of the synthesized compounds was more pronounced compared to baicalein and ivermectin. In contrast to ivermectin and baicalein, bioinformatics investigations were carried out to establish the possible binding interactions between the newly synthesized compounds 2\u20136 and 12 and the active site of 3CLpro. Docking simulations were utilized to identify the binding affinity and binding mode of compounds 2\u20136 and 12 with the active sites of 3CLpro, sPLA2, and cPLA2 enzymes. Our findings demonstrated that all compounds had outstanding binding affinities, especially with the key amino acids of the target enzymes. These findings imply that compound 6 is a potential lead for the development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 quinazoline derivative-based drugs. Compound 6 was shown to have more antiviral activity than baicalein and against 3CLpro. Furthermore, the IC50 value of ivermectin against the SARS-CoV-2 main protease was revealed to be 42.39 \u00b5M, indicating that it has low effectiveness.<\/jats:p>","DOI":"10.3390\/molecules28166052","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T11:07:10Z","timestamp":1692011230000},"page":"6052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Structure Activity Relationship and Molecular Docking of Some Quinazolines Bearing Sulfamerazine Moiety as New 3CLpro, cPLA2, sPLA2 Inhibitors"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1811-2794","authenticated-orcid":false,"given":"Mohammed Abdalla","family":"Hussein","sequence":"first","affiliation":[{"name":"Biotechnology Department, Faculty of Applied Heath Science Technology, October 6 University, Giza 28125, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita M.","family":"Borik","sequence":"additional","affiliation":[{"name":"Chemistry Department, Faculty of Science (Female Section), Jazan University, Jazan 82621, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-6390","authenticated-orcid":false,"given":"Mohamed S.","family":"Nafie","sequence":"additional","affiliation":[{"name":"Chemistry Department (Biochemistry Program), Faculty of Science, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-2272","authenticated-orcid":false,"given":"Heba M.","family":"Abo-Salem","sequence":"additional","affiliation":[{"name":"Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Giza 28125, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4059-2912","authenticated-orcid":false,"given":"Sylvia A.","family":"Boshra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, October 6 University, Giza 28125, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahraa N.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Medical Laboratory Department, Faculty of Applied Medical Sciences, October 6 University, Giza 28125, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023, July 13). WHO Director-General\u2019s Opening Remarks at the Media Briefing on COVID-19\u201411 March 2020. Available online: https:\/\/www.who.int\/director-general\/speeches\/detail\/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1038\/s41467-020-16954-7","article-title":"Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography","volume":"11","author":"Kneller","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.str.2020.10.007","article-title":"Malleability of the SARS-CoV-2 3CL Mpro Active-Site Cavity Facilitates Binding of Clinical Antivirals","volume":"28","author":"Kneller","year":"2020","journal-title":"Structure"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e080921192222","DOI":"10.2174\/2666796702666210311123323","article-title":"Administration of exogenous surfactant and cytosolic phospholipase A2\u03b1 Inhibitors may help COVID-19 infected patients with chronic diseases","volume":"2","author":"Hussein","year":"2021","journal-title":"Coronaviruses"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e00127-20","DOI":"10.1128\/JVI.00127-20","article-title":"Receptor recognition by the novel coronavirus from wuhan: An analysis based on decade-long structural studies of SARS coronavirus","volume":"94","author":"Wan","year":"2020","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1504\/IJBRA.2019.099575","article-title":"Computational protein design of bacteriocins based on structural scaffold of aureocin A53","volume":"15","author":"Talluri","year":"2019","journal-title":"Int. J. Bioinform. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s40267-022-00916-8","article-title":"Plasma lipid profile: A predictive marker of disease severity among COVID-19 patients-an opportunity for low-income countries","volume":"38","author":"Mosaad","year":"2022","journal-title":"Drugs. Ther. Perspect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11779322211055891","DOI":"10.1177\/11779322211055891","article-title":"Plasma Phospholipids: A Promising Simple Biochemical Parameter to Evaluate COVID-19 Infection Severity","volume":"15","author":"Hussein","year":"2021","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_9","first-page":"87","article-title":"Synthesis and biological activities of some novel triazoloquinazolines and triazinoquinazolines containing benzenesulfonamide moieties","volume":"60","author":"Ghorab","year":"2010","journal-title":"Arzneim. Forsch. Drug Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1002\/hc.10187","article-title":"Design, synthesis, and antimicrobial activity of some new pyrazolo[3,4-d]pyrimidines","volume":"14","author":"Ghorab","year":"2003","journal-title":"Heteroat. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"423","DOI":"10.14233\/ajchem.2021.23036","article-title":"Synthesis, Molecular Docking, Biological Potentials and Structure Activity Relationship of New Quinazoline and Quinazoline-4-one Derivatives","volume":"33","author":"Borik","year":"2021","journal-title":"Asian J. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.2174\/1389201022666210601170650","article-title":"A Novel Quinazoline-4-one Derivatives as a Promising Cytokine Inhibitors: Synthesis, Molecular Docking, and Structure-activity Relationship","volume":"23","author":"Borik","year":"2022","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cui, Q., Cheng, H., Xiong, R., Zhang, G., Du, R., Anantpadma, M., Davey, R.A., and Rong, L. (2018). Identification of DiarylQuinoline Compounds as Entry Inhibitors of Ebola Virus. Viruses, 10.","DOI":"10.3390\/v10120678"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7070","DOI":"10.1016\/j.bmc.2011.10.009","article-title":"Quinoline tricyclic derivatives. Design, synthesis and evaluation of the antiviral activity of three new classes of RNA-dependent RNA polymerase inhibitors","volume":"19","author":"Carta","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"127143","DOI":"10.1016\/j.bmcl.2020.127143","article-title":"Design, synthesis and anti-influenza A virus activity of novel 2,4-disubstituted quinazoline derivatives","volume":"30","author":"Wang","year":"2020","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113208","DOI":"10.1016\/j.ejmech.2021.113208","article-title":"Synthesis and antiviral activity of a series of novel quinoline derivatives as anti-RSV or anti-IAV agents","volume":"214","author":"Wang","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.bmc.2011.01.006","article-title":"Synthesis and biological assay of 4-aryl-6-chloro-quinoline derivatives as novel non-nucleoside anti-HBV agents","volume":"19","author":"Guo","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105078","DOI":"10.1016\/j.antiviral.2021.105078","article-title":"A cell-based assay to discover inhibitors of SARS-CoV-2 RNA dependent RNA polymerase","volume":"190","author":"Zhao","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1126\/science.abc1560","article-title":"Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir","volume":"368","author":"Yin","year":"2020","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2165\/00003495-198600321-00005","article-title":"Pharmacological and biochemical actions of sulphasalazine","volume":"32","author":"Hoult","year":"1986","journal-title":"Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"(1987). Nielsen OH, Bukhave K, Elmgreen J, Ahnfelt-Ronne I: Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. Dig. Dis. Sci., 32, 577\u2013582.","DOI":"10.1007\/BF01296156"},{"key":"ref_22","first-page":"S88","article-title":"Therapy of spondylarthropathy in inflammatory bowel disease","volume":"20","author":"Generini","year":"2002","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1046\/j.1365-2036.18.s2.1.x","article-title":"Review article: Mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease","volume":"18","author":"Allgayer","year":"2003","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1016\/S0006-2952(97)00137-8","article-title":"Inhibition of extracellular release of proinflammatory secretory phospholipase A2 (sPLA2) by sulfasalazine: A novel mechanism of anti-inflammatory activity","volume":"53","author":"Pruzanski","year":"1997","journal-title":"Biochem. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1053\/gast.2000.19458","article-title":"Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta","volume":"119","author":"Weber","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1084\/jem.20041948","article-title":"Desreumaux P: Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator-activated receptor-gamma","volume":"201","author":"Rousseaux","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e03227-20","DOI":"10.1128\/mBio.03227-20","article-title":"Baumler AJ: 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-gamma Signaling in the Intestinal Epithelium","volume":"12","author":"Cevallos","year":"2021","journal-title":"mBio"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1172\/JCI992","article-title":"Sulfasalazine: A potent specific inhibitor of nuclear factor kappa B","volume":"101","author":"Wahl","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead- and Drug-like Compounds: The Rule-of-Five Revolution","volume":"1","author":"Lipinski","year":"2004","journal-title":"Drug Discov. Today Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/nrd2445","article-title":"The Influence of Drug-like Concepts on Decision-Making in Medicinal Chemistry","volume":"6","author":"Leeson","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1359-6446(99)01451-8","article-title":"Computational Methods for the Prediction of \u2018Drug-Likeness\u2019","volume":"5","author":"Clark","year":"2000","journal-title":"Drug Discov. Today"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1021\/cn200100h","article-title":"Knowledge-Based, Central Nervous System (CNS) Lead Selection and Lead Optimization for CNS Drug Discovery","volume":"3","author":"Ghose","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1039123","DOI":"10.3389\/fpubh.2022.1039123","article-title":"As the SARS-CoV-2 virus evolves, should Omicron subvariant BA.2 be subjected to quarantine, or should we learn to live with it?","volume":"10","author":"Xu","year":"2022","journal-title":"Front. Public Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.biochi.2014.09.003","article-title":"Emerging roles of secreted phospholipase A2 enzymes: The 3rd edition","volume":"107 Pt A","author":"Murakami","year":"2014","journal-title":"Biochimie"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.bbalip.2019.02.005","article-title":"Novel functions of phospholipase A(2)s: Overview","volume":"1864","author":"Murakami","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13054-019-2336-6","article-title":"Lung fluid biomarkers for acute respiratory distress syndrome: A systematic review and meta-analysis","volume":"23","author":"Wang","year":"2019","journal-title":"Crit. Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/bs.ai.2016.05.001","article-title":"The roles of the secreted phospholipase A(2) gene family in immunology","volume":"132","author":"Murakami","year":"2016","journal-title":"Adv. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.it.2020.02.003","article-title":"Type IIA secreted phospholipase A2 in host defense against bacterial infections","volume":"41","author":"Wu","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3390\/ph13110415","article-title":"Secretory phospholipase A(2)-IIA protein and mRNA pools in extracellular vesicles of bronchoalveolar lavage fluid from patients with early acute respiratory distress syndrome: A new perception in the dissemination of inflammation?","volume":"13","author":"Papadopoulos","year":"2020","journal-title":"Pharmaceuticals"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1084\/jem.20150632","article-title":"Critical role of phospholipase A2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection","volume":"212","author":"Vijay","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18443","DOI":"10.1021\/acsomega.2c00812","article-title":"Biological Evaluation, Molecular Docking Analyses, and ADME Profiling of Certain New Quinazolinones as Anti-colorectal Agents","volume":"7","author":"Almaneai","year":"2022","journal-title":"ACS Omega"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6740","DOI":"10.1016\/j.bmc.2015.09.001","article-title":"Synthesis, in vitro biological activities and in silico study of dihydropyrimidines derivatives","volume":"23","author":"Barakat","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_44","first-page":"14416","article-title":"Carboxamides bearing sulfonamide functionality as potential novel phospholipase A2 inhibitors","volume":"5","author":"Ibezim","year":"2020","journal-title":"Chem. Sel."},{"key":"ref_45","first-page":"887","article-title":"Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation","volume":"123","author":"Gandhirajan","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1124\/jpet.112.201079","article-title":"A novel nontoxic inhibitor of the activation of NADPH oxidase reduces reactive oxygen species production in mouse lung","volume":"345","author":"Lee","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s41232-016-0012-7","article-title":"Metabolic regulation by secreted phospholipase A2","volume":"36","author":"Sato","year":"2016","journal-title":"Inflamm Regen."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.virol.2014.01.030","article-title":"Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection","volume":"454\u2013455","author":"Kelvin","year":"2014","journal-title":"Virology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103499","DOI":"10.1016\/j.arabjc.2021.103499","article-title":"QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches","volume":"15","author":"Jawarkar","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"116393","DOI":"10.1016\/j.bmc.2021.116393","article-title":"Antiviral evaluation of hydroxyethylamine analogs: Inhibitors of SARS-CoV-2 main protease (3CLpro), a virtual screening and simulation approach","volume":"47","author":"Gupta","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1080\/14756366.2020.1801672","article-title":"Flavonoids with inhibitory activity against SARS-CoV-2 3CLpro","volume":"35","author":"Jo","year":"2020","journal-title":"J. Enzyme. Inhib. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.2147\/DDDT.S359009","article-title":"Progress on SARS-CoV-2 3CLpro Inhibitors: Inspiration from SARS-CoV 3CLpro Peptidomimetics and Small-Molecule Anti-Inflammatory Compounds","volume":"16","author":"Zhu","year":"2022","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/s41401-020-0483-6","article-title":"Anti-SARS-CoV-2 Activities in Vitro of Shuanghuanglian Preparations and Bioactive Ingredients","volume":"41","author":"Su","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_54","first-page":"CD010599","article-title":"Anthelmintic drugs for treating ascariasis","volume":"1","author":"Conterno","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Calligari, P., Bobone, S., Ricci, G., and Bocedi, A. (2020). Molecular Investigation of SARS-CoV-2 Proteins and Their Interactions with Antiviral Drugs. Viruses, 12.","DOI":"10.3390\/v12040445"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species severe acute respiratory syndrome related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2","volume":"5","author":"Gorbalenya","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.chempr.2020.04.023","article-title":"Chemistry and biology of SARS-CoV-2","volume":"6","author":"Gao","year":"2020","journal-title":"Chem"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4847","DOI":"10.1093\/nar\/17.12.4847","article-title":"Coronavirus genome: Prediction of putative functional domains in the non-structural polyprotein by comparative amino acid sequence analysis","volume":"17","author":"Gorbalenya","year":"1989","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1099\/0022-1317-81-4-853","article-title":"Virus-encoded proteinases and proteolytic processing in the Nidovirales","volume":"81","author":"Ziebuhr","year":"2000","journal-title":"J. Gen. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/0042-6822(91)90071-I","article-title":"The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase","volume":"180","author":"Lee","year":"1991","journal-title":"Virology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"595097","DOI":"10.3389\/fchem.2020.595097","article-title":"P\u00e9rez-Donoso, Olimpo Garc\u00eda-Beltr\u00e1n8 and Fernando Gonz\u00e1lez-Nilo, In Silico Study of Coumarins and Quinolines Derivatives as Potent Inhibitors of SARS-CoV-2 Main Protease","volume":"8","author":"Osvaldo","year":"2021","journal-title":"Front. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2147\/TCRM.S45412","article-title":"Evaluation of recombinant activated protein C for severe sepsis at a tertiary academic medical center","volume":"9","author":"Anger","year":"2013","journal-title":"Ther. Clin. Risk. Manag."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/s41598-018-37130-4","article-title":"A simple protocol for isolating mouse lung endothelial cells","volume":"9","author":"Wang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/j.bbadis.2015.03.008","article-title":"Effect of azithromycin on the LPS-induced production and secretion of phospholipase A2 in lung cells","volume":"1852","author":"Kitsiouli","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-2269-7_19","article-title":"Small-molecule library screening by docking with PyRx","volume":"1263","author":"Dallakyan","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41586-020-2223-y","article-title":"Structure of Mpro from COVID-19 virus and discovery of its inhibitors","volume":"582","author":"Jin","year":"2020","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nsb0695-458","article-title":"Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2","volume":"2","author":"Schevitz","year":"1995","journal-title":"Nat. Struct. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0092-8674(00)80744-8","article-title":"Crystal structure of human cytosolic phospholipase A2 reveals a novel topology and catalytic mechanism","volume":"97","author":"Dessen","year":"1999","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web toolto evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/16\/6052\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:33:22Z","timestamp":1760128402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/16\/6052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,14]]},"references-count":69,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["molecules28166052"],"URL":"https:\/\/doi.org\/10.3390\/molecules28166052","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,14]]}}}