{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T21:23:46Z","timestamp":1769635426687,"version":"3.49.0"},"reference-count":66,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Transylvania University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioTech"],"abstract":"<jats:p>Antibiotic resistance is a critical problem that results in a high morbidity and mortality rate. The process of discovering new chemotherapy and antibiotics is challenging, expensive, and time-consuming, with only a few getting approved for clinical use. Therefore, screening already-approved drugs to combat pathogens such as bacteria that cause serious infections in humans and animals is highly encouraged. In this work, we aim to identify approved antibiotics that can inhibit the mecA antibiotic resistance gene found in methicillin-resistant Staphylococcus aureus (MRSA) strains. The MecA protein sequence was utilized to perform a BLAST search against a drug database containing 4302 approved drugs. The results revealed that 50 medications, including known antibiotics for other bacterial strains, targeted the mecA antibiotic resistance gene. In addition, a structural similarity approach was employed to identify existing antibiotics for S. aureus, followed by molecular docking. The results of the docking experiment indicated that six drugs had a high binding affinity to the mecA antibiotic resistance gene. Furthermore, using the structural similarity strategy, it was discovered that afamelanotide, an approved drug with unclear antibiotic activity, had a strong binding affinity to the MRSA-MecA protein. These findings suggest that certain already-approved drugs have potential in chemotherapy against drug-resistant pathogenic bacteria, such as MRSA.<\/jats:p>","DOI":"10.3390\/biotech12020025","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T08:27:27Z","timestamp":1680251247000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Computational Screening of Approved Drugs for Inhibition of the Antibiotic Resistance Gene mecA in Methicillin-Resistant Staphylococcus aureus (MRSA) Strains"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6347-3831","authenticated-orcid":false,"given":"Benson","family":"Otarigho","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mofolusho O.","family":"Falade","sequence":"additional","affiliation":[{"name":"Department of Biology, Transylvania University, Lexington, KY 40508, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.2147\/IDR.S272733","article-title":"Methicillin-Resistant Staphylococcus aureus (MRSA): One Health Perspective Approach to the Bacterium Epidemiology, Virulence Factors, Antibiotic-Resistance, and Zoonotic Impact","volume":"13","author":"Algammal","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41579-018-0147-4","article-title":"Methicillin-resistant Staphylococcus aureus: An overview of basic and clinical research","volume":"17","author":"Turner","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.3201\/eid2110.141914","article-title":"Methicillin-susceptible, vancomycin-resistant Staphylococcus aureus, Brazil","volume":"21","author":"Panesso","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S176","DOI":"10.1086\/653518","article-title":"Staphylococcus aureus: Methicillin-susceptible S. aureus to methicillin-resistant S. aureus and vancomycin-resistant S. aureus","volume":"51","author":"Rehm","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","first-page":"1","article-title":"Methicillin-resistant Staphylococcus aureus","volume":"4","author":"Lee","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_6","unstructured":"Centers for Disease Control and Prevention (CDC) (2019). Deadly Staph Infections Still Threaten the US, Retrieved November."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1172\/JCI38226","article-title":"Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era","volume":"119","author":"DeLeo","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tang, Y.-W., Sussman, M., Liu, D., Poxton, I., and Schwartzman, J. (2015). Molecular Medical Microbiology, Elsevier. [2nd ed.].","DOI":"10.1016\/B978-0-12-397169-2.00001-9"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104915","DOI":"10.1016\/j.micpath.2021.104915","article-title":"Emerging resistance mechanisms for 4 types of common anti-MRSA antibiotics in Staphylococcus aureus: A comprehensive review","volume":"156","author":"Liu","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1016\/j.drudis.2019.06.014","article-title":"Drug repurposing: A promising tool to accelerate the drug discovery process","volume":"24","author":"Parvathaneni","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fcimb.2019.00193","article-title":"Drug repurposing to fight colistin and carbapenem-resistant bacteria","volume":"9","author":"Peyclit","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cytogfr.2022.04.007","article-title":"Old drugs, new tricks: Emerging role of drug repurposing in the management of atopic dermatitis","volume":"65","author":"Prasannanjaneyulu","year":"2022","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2174\/1389450116666150806124110","article-title":"New antimicrobial approaches: Reuse of old drugs","volume":"17","author":"Savoia","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s00253-012-4609-8","article-title":"Antimicrobials, drug discovery, and genome mining","volume":"97","author":"Scheffler","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/ilar.51.3.233","article-title":"Methicillin-resistant Staphylococcus aureus in animals","volume":"51","author":"Weese","year":"2010","journal-title":"ILAR J."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Graveland, H., Wagenaar, J.A., Bergs, K., Heesterbeek, H., and Heederik, D. (2011). Persistence of livestock associated MRSA CC398 in humans is dependent on intensity of animal contact. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016830"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e003272","DOI":"10.1136\/bmjopen-2013-003272","article-title":"Risk factors for persistence of livestock-associated MRSA and environmental exposure in veal calf farmers and their family members: An observational longitudinal study","volume":"3","author":"Bos","year":"2013","journal-title":"BMJ Open"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3947\/ic.2016.48.4.267","article-title":"Treatment of methicillin-resistant Staphylococcus aureus bacteremia","volume":"48","author":"Choo","year":"2016","journal-title":"Infect. Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00020-18","DOI":"10.1128\/CMR.00020-18","article-title":"Methicillin-resistant Staphylococcus aureus: Molecular characterization, evolution, and epidemiology","volume":"31","author":"Lakhundi","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ba\u00ebtz, B., Boudrioua, A., Hartke, A., and Giraud, C. (2021). Alternatives to fight vancomycin-resistant staphylococci and enterococci. Antibiotics, 10.","DOI":"10.3390\/antibiotics10091116"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"113","DOI":"10.6026\/97320630014113","article-title":"Analysis of antibiotics resistant genes in different strains of Staphylococcus aureus","volume":"14","author":"Otarigho","year":"2018","journal-title":"Bioinformation"},{"key":"ref_22","unstructured":"Humphreys, H. (2012). Staphylococcus: Skin Infections; Osteomyelitis; Bloodstream Infection; Food Poisoning; Foreign Body Infections; MRSA, in Medical Microbiology, Elsevier."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4352","DOI":"10.1128\/AAC.00356-10","article-title":"Origin and molecular evolution of the determinant of methicillin resistance in staphylococci","volume":"54","author":"Tsubakishita","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1128\/CMR.3.1.13","article-title":"Discovery and development of new antimicrobial agents","volume":"3","author":"Gootz","year":"1990","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ejmech.2018.11.052","article-title":"Boosting the efficacy of anti-MRSA \u03b2-lactam antibiotics via an easily accessible, non-cytotoxic and orally bioavailable FtsZ inhibitor","volume":"163","author":"Lui","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41429-023-00594-2","article-title":"Drug repurposing strategy II: From approved drugs to agri-fungicide leads","volume":"76","author":"An","year":"2023","journal-title":"J. Antibiot."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13866","DOI":"10.1038\/s41598-020-70863-9","article-title":"An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors","volume":"10","author":"Trezza","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1159\/000238445","article-title":"Effect of 5-fluorouracil, mitoxantrone, methotrexate, and vincristine on the antibacterial activity of ceftriaxone, ceftazidime, cefotiam, piperacillin, and netilmicin","volume":"32","author":"Gieringer","year":"1986","journal-title":"Chemotherapy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2217\/fmb.14.3","article-title":"Promises and failures of gallium as an antibacterial agent","volume":"9","author":"Minandri","year":"2014","journal-title":"Future Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e30120","DOI":"10.7554\/eLife.30120","article-title":"Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control","volume":"6","author":"Carroni","year":"2017","journal-title":"Elife"},{"key":"ref_32","first-page":"870","article-title":"Structural basis for the \u03b2 lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus","volume":"9","author":"Lim","year":"2002","journal-title":"Nat. Struct. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1107\/S1744309106009742","article-title":"Structure of the MecI repressor from Staphylococcus aureus in complex with the cognate DNA operator of mec","volume":"62","author":"Safo","year":"2006","journal-title":"Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D313","DOI":"10.1093\/nar\/gkw1132","article-title":"The SWISS-MODEL Repository\u2014New features and functionality","volume":"45","author":"Bienert","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1002\/elps.200900140","article-title":"Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective","volume":"30","author":"Guex","year":"2009","journal-title":"Electrophoresis"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: More and better reference data for improved all-atom structure validation","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"W159","DOI":"10.1093\/nar\/gkac394","article-title":"CB-Dock2: Improved protein\u2013ligand blind docking by integrating cavity detection, docking and homologous template fitting","volume":"50","author":"Liu","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_39","first-page":"1","article-title":"Methicillin-resistant Staphylococcus aureus (MRSA): Burden of disease and control challenges in Europe","volume":"15","author":"Becker","year":"2010","journal-title":"Eurosurveillance"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ijantimicag.2011.09.030","article-title":"Meticillin-resistant Staphylococcus aureus (MRSA): Global epidemiology and harmonisation of typing methods","volume":"39","author":"Stefani","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1128\/jb.171.5.2882-2885.1989","article-title":"Expression and inducibility in Staphylococcus aureus of the mecA gene, which encodes a methicillin-resistant S. aureus-specific penicillin-binding protein","volume":"171","author":"Ubukata","year":"1989","journal-title":"J. Bacteriol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cmrp.2018.01.001","article-title":"Methicillin-resistant Staphylococcus aureus: An update on the epidemiology, treatment options and infection control","volume":"8","author":"Boswihi","year":"2018","journal-title":"Curr. Med. Res. Pract."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e2208378119","DOI":"10.1073\/pnas.2208378119","article-title":"Breaking down antibiotic resistance in methicillin-resistant Staphylococcus aureus: Combining antimicrobial photodynamic and antibiotic treatments","volume":"119","author":"Willis","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1007\/s11224-022-01975-3","article-title":"Repurposing FDA approved drugs as possible anti-SARS-CoV-2 medications using ligand-based computational approaches: Sum of ranking difference-based model selection","volume":"33","author":"De","year":"2022","journal-title":"Struct. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/j.drudis.2022.03.006","article-title":"Structure-based drug repurposing: Traditional and advanced AI\/ML-aided methods","volume":"27","author":"Choudhury","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3389\/fmicb.2019.00041","article-title":"Drug repurposing for the treatment of bacterial and fungal infections","volume":"10","author":"Smani","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"112312","DOI":"10.1016\/j.ejmech.2020.112312","article-title":"Penicillin binding protein 2a: An overview and a medicinal chemistry perspective","volume":"199","author":"Shalaby","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1093\/clinids\/5.Supplement_1.S108","article-title":"Cefoperazone: A review of its antimicrobial spectrum, \u03b2-lactamase stability, enzyme inhibition, and other in vitro characteristics","volume":"5","author":"Jones","year":"1983","journal-title":"Rev. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1128\/AAC.18.1.195","article-title":"Affinity of cefoperazone for penicillin-binding proteins","volume":"18","author":"Matsubara","year":"1980","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1136\/jnnp.64.3.379","article-title":"Treatment of accidental high dose intraventricular mezlocillin application by cerebrospinal fluid exchange","volume":"64","author":"Kristof","year":"1998","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/PL00012156","article-title":"In-vitro antibacterial activities of cefpiramide and other broad-spectrum antibiotics against 440 clinical isolates in China","volume":"6","author":"Wang","year":"2000","journal-title":"J. Infect. Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s40265-013-0168-2","article-title":"Ceftolozane\/tazobactam: A novel cephalosporin\/\u03b2-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli","volume":"74","author":"Zhanel","year":"2014","journal-title":"Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1128\/AAC.06349-11","article-title":"Pharmacokinetics and safety of intravenous ceftolozane-tazobactam in healthy adult subjects following single and multiple ascending doses","volume":"56","author":"Miller","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1128\/AAC.00329-06","article-title":"Randomized, open-label, comparative study of piperacillin-tazobactam administered by continuous infusion versus intermittent infusion for treatment of hospitalized patients with complicated intra-abdominal infection","volume":"50","author":"Lau","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1517\/17425255.2010.506187","article-title":"Pharmacokinetic evaluation of piperacillin-tazobactam","volume":"6","author":"Hayashi","year":"2010","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"ii23","DOI":"10.1093\/jac\/dkh205","article-title":"Pharmacokinetics and pharmacodynamics of ertapenem: An overview for clinicians","volume":"53","author":"Nix","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/S1473-3099(21)00625-3","article-title":"Efficacy of ertapenem, gentamicin, fosfomycin, and ceftriaxone for the treatment of anogenital gonorrhoea (NABOGO): A randomised, non-inferiority trial","volume":"22","author":"Jongen","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/jac\/dkl393","article-title":"Bactericidal agents in the treatment of MRSA infections\u2014The potential role of daptomycin","volume":"58","author":"French","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0195-6701(98)90078-0","article-title":"Limited effectiveness of chlorhexidine based hand disinfectants against methicillin-resistant Staphylococcus aureus (MRSA)","volume":"38","author":"Kampf","year":"1998","journal-title":"J. Hosp. Infect."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.ijantimicag.2015.08.014","article-title":"In vitro activity of oritavancin and comparator agents against staphylococci, streptococci and enterococci from clinical infections in Europe and North America, 2011\u20132014","volume":"46","author":"Biedenbach","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jmb.2008.01.031","article-title":"Oritavancin exhibits dual mode of action to inhibit cell-wall biosynthesis in Staphylococcus aureus","volume":"377","author":"Kim","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S214","DOI":"10.1093\/cid\/cir920","article-title":"Oritavancin: Mechanism of action","volume":"54","author":"Zhanel","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ymgme.2019.01.020","article-title":"Erythropoietic Protoporphyria and X-Linked Protoporphyria: Pathophysiology, genetics, clinical manifestations, and management","volume":"128","author":"Balwani","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s40262-016-0501-5","article-title":"Pharmacokinetics and pharmacodynamics of afamelanotide and its clinical use in treating dermatologic disorders","volume":"56","author":"Minder","year":"2017","journal-title":"Clin. Pharmacokinet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s40257-016-0184-6","article-title":"Afamelanotide: A review in erythropoietic protoporphyria","volume":"17","author":"Kim","year":"2016","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1056\/NEJMoa1411481","article-title":"Afamelanotide for erythropoietic protoporphyria","volume":"373","author":"Langendonk","year":"2015","journal-title":"N. Engl. J. Med."}],"container-title":["BioTech"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-6284\/12\/2\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:07:21Z","timestamp":1760123241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-6284\/12\/2\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":66,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["biotech12020025"],"URL":"https:\/\/doi.org\/10.3390\/biotech12020025","relation":{},"ISSN":["2673-6284"],"issn-type":[{"value":"2673-6284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]}}}