{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T01:16:48Z","timestamp":1775179008828,"version":"3.50.1"},"reference-count":14,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A5A2017476"],"award-info":[{"award-number":["NRF-2020R1A5A2017476"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF- 2021R1A2C2006961"],"award-info":[{"award-number":["NRF- 2021R1A2C2006961"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["6634-325-320-01"],"award-info":[{"award-number":["6634-325-320-01"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A5A2017476"],"award-info":[{"award-number":["NRF-2020R1A5A2017476"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF- 2021R1A2C2006961"],"award-info":[{"award-number":["NRF- 2021R1A2C2006961"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["6634-325-320-01"],"award-info":[{"award-number":["6634-325-320-01"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Korea National Institute of Health, the Korea Disease Control and Prevention Agency","award":["NRF-2020R1A5A2017476"],"award-info":[{"award-number":["NRF-2020R1A5A2017476"]}]},{"name":"the Korea National Institute of Health, the Korea Disease Control and Prevention Agency","award":["NRF- 2021R1A2C2006961"],"award-info":[{"award-number":["NRF- 2021R1A2C2006961"]}]},{"name":"the Korea National Institute of Health, the Korea Disease Control and Prevention Agency","award":["6634-325-320-01"],"award-info":[{"award-number":["6634-325-320-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The ongoing COVID-19 pandemic highlights the urgent need for effective antiviral agents and vaccines. Drug repositioning, which involves modifying existing drugs, offers a promising approach for expediting the development of novel therapeutics. In this study, we developed a new drug, MDB-MDB-601a-NM, by modifying the existing drug nafamostat (NM) with the incorporation of glycyrrhizic acid (GA). We assessed the pharmacokinetic profiles of MDB-601a-NM and nafamostat in Sprague-Dawley rats, revealing rapid clearance of nafamostat and sustained drug concentration of MDB-601a-NM after subcutaneous administration. Single-dose toxicity studies showed potential toxicity and persistent swelling at the injection site with high-dose administration of MDB-601a-NM. Furthermore, we evaluated the efficacy of MDB-601a-NM in protecting against SARS-CoV-2 infection using the K18 hACE-2 transgenic mouse model. Mice treated with 60 mg\/kg and 100 mg\/kg of MDB-601a-NM exhibited improved protectivity in terms of weight loss and survival rates compared to the nafamostat-treated group. Histopathological analysis revealed dose-dependent improvements in histopathological changes and enhanced inhibitory efficacy in MDB-601a-NM-treated groups. Notably, no viral replication was detected in the brain tissue when mice were treated with 60 mg\/kg and 100 mg\/kg of MDB-601a-NM. Our developed MDB-601a-NM, a modified Nafamostat with glycyrrhizic acid, shows improved protectivity against SARS-CoV-2 infection. Its sustained drug concentration after subcutaneous administration and dose-dependent improvements makes it a promising therapeutic option.<\/jats:p>","DOI":"10.3390\/ijms24119579","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T03:06:00Z","timestamp":1685588760000},"page":"9579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the Antiviral Efficacy of Subcutaneous Nafamostat Formulated with Glycyrrhizic Acid against SARS-CoV-2 in a Murine Model"],"prefix":"10.3390","volume":"24","author":[{"given":"Ju Hwan","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju-si 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woong Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"MODNBIO Inc., Seoul 08378, Republic of Korea"},{"name":"Institute of Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Cheol","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju-si 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beom Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju-si 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"On Bi","family":"Park","sequence":"additional","affiliation":[{"name":"Biomedical Engineering from the Department of Biotechnology, Graduate School of Advanced Fusion Technology, Cheongju University, Cheongju-si 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santosh","family":"Chokkakula","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju-si 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Ju","family":"Ahn","sequence":"additional","affiliation":[{"name":"Biomedical Engineering from the Department of Biotechnology, Graduate School of Advanced Fusion Technology, Cheongju University, Cheongju-si 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9661-6392","authenticated-orcid":false,"given":"Sol","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju-si 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju-si 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Won","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Medical Engineering, Catholic University of Daegu (DCU), Gyeongsan-si 38430, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Min","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Medical IT, Catholic Kwandong University, Gangneung-si 25601, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eung-Gook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6073-0783","authenticated-orcid":false,"given":"Min-Suk","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju-si 28644, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020, January 30). 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