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Viruses. 2018 Apr 20;10(4). pii: E211. doi: 10.3390/v10040211.

Gemcitabine and Nucleos(t)ide Synthesis Inhibitors Are Broad-Spectrum Antiviral Drugs that Activate Innate Immunity.

Author information

1
Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon-si 34114, Korea. shinhy@krict.re.kr.
2
Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, 141 Gajeong-ro, Yuseong-gu, Daejeon-si 34114, Korea. chonskim@krict.re.kr.
3
Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungbuk 28116, Korea. sungchan@kribb.re.kr.
4
Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science and Technology, 217 Gajeong-ro, Yuseong-gu, Daejeon-si 34113, Korea. sungchan@kribb.re.kr.

Abstract

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.

KEYWORDS:

antiviral drugs; gemcitabine; innate immunity; interferon-stimulated gene; nucleos(t)ide synthesis; nucleoside analog

PMID:
29677162
PMCID:
PMC5923505
DOI:
10.3390/v10040211
[Indexed for MEDLINE]
Free PMC Article

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