{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:36:09Z","timestamp":1789673769305,"version":"4.0.1"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanxi Provincial Research Foundation for Basic Research","award":["202103021224236"],"award-info":[{"award-number":["202103021224236"]}]},{"name":"Shanxi Provincial Research Foundation for Basic Research","award":["2021YFC2301603"],"award-info":[{"award-number":["2021YFC2301603"]}]},{"name":"National Key R&amp;D program","award":["202103021224236"],"award-info":[{"award-number":["202103021224236"]}]},{"name":"National Key R&amp;D program","award":["2021YFC2301603"],"award-info":[{"award-number":["2021YFC2301603"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Angiotensin-converting enzyme 2 (ACE2) is a key mediator of SARS-CoV-2 host cell entry, making it an attractive target for drug delivery strategies. Nafamostat (NM), a multifunctional agent with antiviral and anti-inflammatory properties, holds promise for COVID-19 treatment. In this study, we developed PLGA-PEG nanoparticles encapsulating NM (NM-PP NPs) and further conjugated them with specific ACE2 decoys (CTC-445.2d or SI5\u03b1) to generate NM-PP-Pro\/Pep NPs. Both unmodified and ACE2-decoy-modified NPs exhibited uniform size distributions (diameter &lt; 200 nm) and negative surface charges, as confirmed by dynamic light scattering and zeta potential measurements. The nanoparticles maintained structural integrity for at least 18 days at 4 \u00b0C and room temperature. In vitro release studies revealed sustained and controlled NM release kinetics. Notably, NM-PP-Pro NPs displayed potent antiviral activity, with an IC50 &lt; 0.05 nM against wild-type SARS-CoV-2 and remained effective against the D614G variant (IC50 = 2 nM). These results underscore the potential of NM-PP-Pro NPs as a versatile nanotherapeutic platform for targeting SARS-CoV-2 and its emerging variants.<\/jats:p>","DOI":"10.3390\/v17091167","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T15:49:34Z","timestamp":1756309774000},"page":"1167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["ACE2-Decoy-Conjugated PLGA-PEG Nanoparticles Loaded with Nafamostat for Potent Antiviral Activity"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3349-249X","authenticated-orcid":false,"given":"Shulin","family":"Hou","sequence":"first","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China"},{"name":"Academy of Medical Sciences, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China"},{"name":"Academy of Medical Sciences, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruining","family":"Li","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China"},{"name":"Academy of Medical Sciences, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoran","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Qiao","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2449-057X","authenticated-orcid":false,"given":"Xiaozheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Department of Biochemistry and Molecular Biology, College of Basic Medicine, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/s41586-024-08315-x","article-title":"Evolving antibody response to SARS-CoV-2 antigenic shift from XBB to JN.1","volume":"637","author":"Jian","year":"2025","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ma, Y., Xu, S., Luo, Y., Peng, J., Guo, J., Dong, A., Xu, Z., Li, J., Lei, L., and He, L. (2023). Predicting the transmission dynamics of novel coronavirus infection in Shanxi province after the implementation of the \u201cClass B infectious disease Class B management\u201d policy. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1322430"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Dinata, R., Baindara, P., and Mandal, S.M. (2025). Evolution of Antiviral Drug Resistance in SARS-CoV-2. Viruses, 17.","DOI":"10.3390\/v17050722"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1056\/NEJMsb2506929","article-title":"An Evidence-Based Approach to Covid-19 Vaccination","volume":"392","author":"Prasad","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1056\/NEJMoa2107659","article-title":"Safety and Efficacy of NVX-CoV2373 COVID-19 Vaccine","volume":"385","author":"Heath","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, M.Y., Zhao, R., Gao, L.J., Gao, X.F., Wang, D.P., and Cao, J.M. (2020). SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development. Front. Cell Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.587269"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Guo, J., Luo, Y., Ma, Y., Xu, S., Li, J., Wang, T., Lei, L., He, L., Yu, H., and Xie, J. (2024). Assessing the impact of vaccination and medical resource allocation on infectious disease outbreak management: A case study of COVID-19 in Taiyuan City. Front. Public Health, 12.","DOI":"10.3389\/fpubh.2024.1368876"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.7326\/M23-2887","article-title":"Rebound of COVID-19 With Nirmatrelvir-Ritonavir Antiviral Therapy","volume":"176","author":"Cohen","year":"2023","journal-title":"Ann. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s40265-022-01684-5","article-title":"Molnupiravir: First Approval","volume":"82","author":"Syed","year":"2022","journal-title":"Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tian, L., Pang, Z., Li, M., Lou, F., An, X., Zhu, S., Song, L., Tong, Y., Fan, H., and Fan, J. (2022). Molnupiravir and Its Antiviral Activity Against COVID-19. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.855496"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s40265-024-02039-y","article-title":"Ensitrelvir Fumaric Acid: First Approval","volume":"84","author":"Syed","year":"2024","journal-title":"Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Van Egeren, D., Stoddard, M., White, L.F., Hochberg, N.S., Rogers, M.S., Zetter, B., Joseph-McCarthy, D., and Chakravarty, A. (2023). Vaccines Alone Cannot Slow the Evolution of SARS-CoV-2. Vaccines, 11.","DOI":"10.3390\/vaccines11040853"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Focosi, D., Franchini, M., Maggi, F., and Shoham, S. (2024). COVID-19 therapeutics. Clin. Microbiol. Rev., 37.","DOI":"10.1128\/cmr.00119-23"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1021\/acsinfecdis.3c00125","article-title":"Systematic Analyses of the Resistance Potential of Drugs Targeting SARS-CoV-2 Main Protease","volume":"9","author":"Flynn","year":"2023","journal-title":"ACS Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev-virology-110615-042301","article-title":"Structure, Function, and Evolution of Coronavirus Spike Proteins","volume":"3","author":"Li","year":"2016","journal-title":"Ann. Rev. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2111199119","DOI":"10.1073\/pnas.2111199119","article-title":"SARS-CoV-2 spike engagement of ACE2 primes S2\u2019 site cleavage and fusion initiation","volume":"119","author":"Yu","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.str.2022.09.003","article-title":"Hold your horses: The receptor-binding domains of SARS-CoV-2, SARS-CoV, and hCoV-NL63 bind equine ACE2","volume":"30","author":"Nawrath","year":"2022","journal-title":"Structure"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2363","DOI":"10.1002\/rmv.2363","article-title":"Potential intestinal infection and faecal-oral transmission of human coronaviruses","volume":"32","author":"Ning","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e107821","DOI":"10.15252\/embj.2021107821","article-title":"TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells","volume":"40","author":"Koch","year":"2021","journal-title":"EMBO J."},{"key":"ref_22","first-page":"1889","article-title":"Screening of Potential Inhibitors Against SARS-CoV-2 Based on Prescription Mining and Molecular Dynamics Simulations","volume":"49","author":"Zhang","year":"2022","journal-title":"Prog. Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, J., Liu, F., Wu, F., Su, X., Zhang, L., Zhao, X., Shang, C., Han, L., Zhang, Y., and Xiao, Z. (2024). Inhibition of multiple SARS-CoV-2 variants entry by Lycium barbarum L. polysaccharides through disruption of spike protein-ACE2 interaction. Int. J. Biol. Macromol., 261.","DOI":"10.1016\/j.ijbiomac.2024.129785"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00705-025-06327-0","article-title":"ACE2, a therapeutic target of COVID-19, needs to be treated with caution","volume":"170","author":"Liu","year":"2025","journal-title":"Arch. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.1021\/acsnano.4c10708","article-title":"Trained Decoy Nanocages Confer Selective Cuproptosis and Metabolic Reprogramming for Drug-Resistant Bacterial Targeting Therapy","volume":"19","author":"Zhang","year":"2025","journal-title":"ACS Nano"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Maniak, H., Talma, M., and Giurg, M. (2021). Inhibitory Potential of New Phenolic Hydrazide-Hydrazones with a Decoy Substrate Fragment towards Laccase from a Phytopathogenic Fungus: SAR and Molecular Docking Studies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212307"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s40262-013-0072-7","article-title":"Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects","volume":"52","author":"Haschke","year":"2013","journal-title":"Clin. Pharmacokinet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e15230","DOI":"10.15252\/emmm.202115230","article-title":"Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants","volume":"14","author":"Wirnsberger","year":"2022","journal-title":"EMBO Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1126\/science.abc0870","article-title":"Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2","volume":"369","author":"Chan","year":"2020","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhao, H., and An, Y. (2021). ACE2 Shedding and the Role in COVID-19. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.789180"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.4049\/jimmunol.2100144","article-title":"Selective Inhibition of the Interaction between SARS-CoV-2 Spike S1 and ACE2 by SPIDAR Peptide Induces Anti-Inflammatory Therapeutic Responses","volume":"207","author":"Paidi","year":"2021","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14955","DOI":"10.1021\/acs.jmedchem.1c00655","article-title":"Computational Design of Potent D-Peptide Inhibitors of SARS-CoV-2","volume":"64","author":"Valiente","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pei, P., Qin, H., Chen, J., Wang, F., He, C., He, S., Hong, B., Liu, K., Qiao, R., and Fan, H. (2021). Computational design of ultrashort peptide inhibitors of the receptor-binding domain of the SARS-CoV-2 S protein. Brief. Bioinform., 22.","DOI":"10.1093\/bib\/bbab298"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eabn7737","DOI":"10.1126\/scitranslmed.abn7737","article-title":"An engineered ACE2 decoy neutralizes the SARS-CoV-2 Omicron variant and confers protection against infection in vivo","volume":"14","author":"Ikemura","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.abe0075","article-title":"De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2","volume":"370","author":"Linsky","year":"2020","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e12050","DOI":"10.1002\/jev2.12050","article-title":"Extracellular vesicles containing ACE2 efficiently prevent infection by SARS-CoV-2 Spike protein-containing virus","volume":"10","author":"Cocozza","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Fang, J.Y., Huang, K.Y., Wang, T.H., Lin, Z.C., Chen, C.C., Chang, S.Y., Chen, E.L., Chao, T.L., Yang, S.C., and Yang, P.C. (2024). Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02435-2"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Neary, M., Sharp, J., Gallardo-Toledo, E., Herriott, J., Kijak, E., Bramwell, C., Cox, H., Tatham, L., Box, H., and Curley, P. (2023). Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters. Viruses, 15.","DOI":"10.3390\/v15081744"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6532","DOI":"10.1128\/AAC.01043-16","article-title":"Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay","volume":"60","author":"Yamamoto","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yamamoto, M., Kiso, M., Sakai-Tagawa, Y., Iwatsuki-Horimoto, K., Imai, M., Takeda, M., Kinoshita, N., Ohmagari, N., Gohda, J., and Semba, K. (2020). The Anticoagulant Nafamostat Potently Inhibits SARS-CoV-2 S Protein-Mediated Fusion in a Cell Fusion Assay System and Viral Infection In Vitro in a Cell-Type-Dependent Manner. Viruses, 12.","DOI":"10.3390\/v12060629"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1111\/jth.14858","article-title":"Potential of heparin and nafamostat combination therapy for COVID-19","volume":"18","author":"Asakura","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1152\/physrev.00013.2020","article-title":"Elevated Plasmin (ogen) as a Common Risk Factor for COVID-19 Susceptibility","volume":"100","author":"Ji","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1254\/jjp.35.203","article-title":"Pharmacological studies of FUT-175, nafamstat mesilate I. Inhibition of protease activity in in vitro and in vivo experiments","volume":"35","author":"Aoyama","year":"1984","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"106922","DOI":"10.1016\/j.ijantimicag.2023.106922","article-title":"Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicentre randomized controlled clinical trial","volume":"62","author":"Okugawa","year":"2023","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s00216-008-2054-4","article-title":"A method for quantifying the unstable and highly polar drug nafamostat mesilate in human plasma with optimized solid-phase extraction and ESI-MS detection: More accurate evaluation for pharmacokinetic study","volume":"391","author":"Cao","year":"2008","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1248\/yakushi1947.105.5_512","article-title":"Stability studies on nafamstat mesilate in aqueous solution. I. Kinetic studies in various pH and temperature conditions","volume":"105","author":"Arakawa","year":"1985","journal-title":"Yakugaku Zasshi."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Rai, G., Gauba, P., Tyagi, A., and Dang, S. (Drug Deliv. Transl. Res., 2025). Lactoferrin-modified PLGA nanoparticles for pregabalin: Development, characterization, in vitro targeting and pharmacodynamic evaluation, Drug Deliv. Transl. Res., online ahead of print.","DOI":"10.1007\/s13346-025-01848-2"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.jconrel.2023.10.050","article-title":"Drug repurposing for the treatment of COVID-19: Targeting nafamostat to the lungs by a liposomal delivery system","volume":"364","author":"Rai","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lo, Y.C., and Lin, W.J. (2023). Improve BBB Penetration and Cytotoxicity of Palbociclib in U87-MG Glioblastoma Cells Delivered by Dual Peptide Functionalized Nanoparticles. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15102429"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41421-023-00585-5","article-title":"Dosing interval regimen shapes potency and breadth of antibody repertoire after vaccination of SARS-CoV-2 RBD protein subunit vaccine","volume":"9","author":"Guo","year":"2023","journal-title":"Cell Discov."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kelle, D., Speth, K.R., Mart\u00ednez-Negro, M., Mail\u00e4nder, V., Landfester, K., and Iyisan, B. (2025). Effect of protein corona on drug release behavior of PLGA nanoparticles. Eur. J. Pharm. Biopharm., 207.","DOI":"10.1016\/j.ejpb.2024.114611"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.actbio.2025.05.012","article-title":"IL-21R-Targeted Nano-immunosuppressant Prevents Acute Rejection in Allogeneic Transplantation by Blocking Maturation of T Follicular Helper Cells","volume":"199","author":"Zeng","year":"2025","journal-title":"Acta Biomater."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e2207604","DOI":"10.1002\/smll.202207604","article-title":"Boosting Glioblastoma Therapy with Targeted Pyroptosis Induction","volume":"19","author":"Fang","year":"2023","journal-title":"Small"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ejim.2020.04.037","article-title":"The pivotal link between ACE2 deficiency and SARS-CoV-2 infection","volume":"76","author":"Verdecchia","year":"2020","journal-title":"Eur. J. Intern. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mehrabadi, M.E., Hemmati, R., Tashakor, A., Homaei, A., Yousefzadeh, M., Hemati, K., and Hosseinkhani, S. (2021). Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity. Biomed. Pharmacother., 137.","DOI":"10.1016\/j.biopha.2021.111363"},{"key":"ref_57","first-page":"36","article-title":"The Balance between Two Branches of RAS Can Protect from Severe COVID-19 Course","volume":"15","author":"Bobkova","year":"2021","journal-title":"Biochem. Suppl. Ser. A Membr. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1093\/cvr\/cvaa133","article-title":"Targeting mitochondrial fission as a potential therapeutic for abdominal aortic aneurysm","volume":"117","author":"Cooper","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Kuba, K., Yamaguchi, T., and Penninger, J.M. (2021). Angiotensin-Converting Enzyme 2 (ACE2) in the Pathogenesis of ARDS in COVID-19. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.732690"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/j.1365-2362.2009.02153.x","article-title":"SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS","volume":"39","author":"Oudit","year":"2009","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1053\/j.gastro.2020.05.030","article-title":"Age, Inflammation, and Disease Location Are Critical Determinants of Intestinal Expression of SARS-CoV-2 Receptor ACE2 and TMPRSS2 in Inflammatory Bowel Disease","volume":"159","author":"Nowak","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/nano.202100123","article-title":"Broad antiviral and anti-inflammatory efficacy of nafamostat against SARS-CoV-2 and seasonal coronaviruses in primary human bronchiolar epithelia","volume":"3","author":"Niemeyer","year":"2022","journal-title":"Nano Sel."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.ijid.2020.10.093","article-title":"Potential mechanisms of nafamostat therapy for severe COVID-19 pneumonia with disseminated intravascular coagulation","volume":"102","author":"Takahashi","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/j.mayocp.2020.06.018","article-title":"Targeting TMPRSS2 in SARS-CoV-2 Infection","volume":"95","author":"Baughn","year":"2020","journal-title":"Mayo Clin. Proc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.addr.2007.08.038","article-title":"Controlled drug delivery in tissue engineering","volume":"60","author":"Biondi","year":"2008","journal-title":"Adv. Drug Deliv. Rev."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/9\/1167\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:45Z","timestamp":1760034825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/9\/1167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":65,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["v17091167"],"URL":"https:\/\/doi.org\/10.3390\/v17091167","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,27]]}}}