{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:31:55Z","timestamp":1790652715733,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T00:00:00Z","timestamp":1524182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Nucleoside analogs have been frequently identified as antiviral agents. In recent years, gemcitabine, a cytidine analog in clinical use for the treatment of many solid tumors, was also shown to have antiviral activity against a broad range of viruses. Nucleoside analogs generally interfere with cellular nucleos(t)ide synthesis pathways, resulting in the depletion or imbalance of (d)NTP pools. Intriguingly, a few recent reports have shown that some nucleoside analogs, including gemcitabine, activated innate immunity, inducing the expression of interferon-stimulated genes, through nucleos(t)ide synthesis inhibition. The precise crosstalk between these two independent processes remains to be determined. Nonetheless, we summarize the current knowledge of nucleos(t)ide synthesis inhibition-related innate immunity and propose it as a newly emerging antiviral mechanism of nucleoside analogs.<\/jats:p>","DOI":"10.3390\/v10040211","type":"journal-article","created":{"date-parts":[[2018,4,23]],"date-time":"2018-04-23T04:29:17Z","timestamp":1524457757000},"page":"211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity"],"prefix":"10.3390","volume":"10","author":[{"given":"Hye Jin","family":"Shin","sequence":"first","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon-si 34114, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chonsaeng","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon-si 34114, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7627-978X","authenticated-orcid":false,"given":"Sungchan","family":"Cho","sequence":"additional","affiliation":[{"name":"Anticancer Agent Research Center, Korea Research Institute of Bioscience &amp; Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 28116, Korea"},{"name":"Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon-si 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/nrd4010","article-title":"Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases","volume":"12","author":"Jordheim","year":"2013","journal-title":"Nat. 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