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Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Int+J+Mol+Sci 2021 ; 22 (4): ä Nephropedia Template TP
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Comparison of Antiviral Activity of Gemcitabine with 2 -Fluoro-2 -Deoxycytidine and Combination Therapy with Remdesivir against SARS-CoV-2 #MMPMID33557278
Jang Y; Shin JS; Lee MK; Jung E; An T; Kim UI; Kim K; Kim M
Int J Mol Sci 2021[Feb]; 22 (4): ä PMID33557278show ga
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 (EC(50)) of 1.2 muM, more active than the well-known nucleoside monophosphate remdesivir (EC(50) = 35.4 muM). In contrast, 2FdC was marginally active (EC(50) = 175.2 muM). For all three compounds, the 50% cytotoxic concentration (CC(50)) values were over 300 muM 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.