{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T22:38:46Z","timestamp":1773787126820,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"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-2020M3A9I2081687"],"award-info":[{"award-number":["NRF-2020M3A9I2081687"]}],"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-2020M3A9I2108564"],"award-info":[{"award-number":["NRF-2020M3A9I2108564"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. The virus still spreads globally through human-to-human transmission. Nevertheless, there are no specific treatments clinically approved. This study aimed to compare antiviral activity of gemcitabine and its analogue 2\u2032-fluoro-2\u2032-deoxycytidine (2FdC) against SARS-CoV-2 as well as cytotoxicity in vitro. Fluorescent image-based antiviral assays revealed that gemcitabine was highly potent, with a 50% effective concentration (EC50) of 1.2 \u03bcM, more active than the well-known nucleoside monophosphate remdesivir (EC50 = 35.4 \u03bcM). In contrast, 2FdC was marginally active (EC50 = 175.2 \u03bcM). For all three compounds, the 50% cytotoxic concentration (CC50) values were over 300 \u03bcM toward Vero CCL-81 cells. Western blot and quantitative reverse-transcription polymerase chain reaction analyses verified that gemcitabine blocked viral protein expression in virus-infected cells, not only Vero CCL-81 cells but also Calu-3 human lung epithelial cells in a dose-dependent manner. It was found that gemcitabine has a synergistic effect when combined with remdesivir. This report suggests that the difluoro group of gemcitabine is critical for the antiviral activity and that its combination with other evaluated antiviral drugs, such as remdesivir, could be a desirable option to treat SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3390\/ijms22041581","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T12:02:10Z","timestamp":1612440130000},"page":"1581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Comparison of Antiviral Activity of Gemcitabine with 2\u2032-Fluoro-2\u2032-Deoxycytidine and Combination Therapy with Remdesivir against SARS-CoV-2"],"prefix":"10.3390","volume":"22","author":[{"given":"Yejin","family":"Jang","sequence":"first","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Soo","family":"Shin","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myoung Kyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunhye","family":"Jung","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4356-6827","authenticated-orcid":false,"given":"Timothy","family":"An","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"},{"name":"Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uk-Il","family":"Kim","sequence":"additional","affiliation":[{"name":"Research and Development Center, ST Pharm Co., Ltd., Seoul 01694, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyungjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Research and Development Center, ST Pharm Co., Ltd., Seoul 01694, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2851-5298","authenticated-orcid":false,"given":"Meehyein","family":"Kim","sequence":"additional","affiliation":[{"name":"Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Korea"},{"name":"Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"ref_1","first-page":"825","article-title":"Coronaviridae","volume":"Volume 2","author":"Knife","year":"2013","journal-title":"Fields Virology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Song, Z., Xu, Y., Bao, L., Zhang, L., Yu, P., Qu, Y., Zhu, H., Zhao, W., Han, Y., and Qin, C. 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