期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ijms22041581
关键词
SARS-CoV-2; antiviral activity; gemcitabine; 2′ -fluoro-2′ -deoxycytidine
资金
- National Research Foundation of Korea (NRF) - Korean government (MSIT) [NRF-2020M3A9I2081687, NRF-2020M3A9I2108564]
The study found that gemcitabine has high antiviral activity against SARS-CoV-2, while 2FdC has lower antiviral activity. Both compounds showed low cytotoxicity towards cells.
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 '-fluoro-2 '-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 mu M, more active than the well-known nucleoside monophosphate remdesivir (EC50 = 35.4 mu M). In contrast, 2FdC was marginally active (EC50 = 175.2 mu M). For all three compounds, the 50% cytotoxic concentration (CC50) values were over 300 mu M 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.
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