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. 2020 Dec;9(1):1170-1173.
doi: 10.1080/22221751.2020.1772676.

Gemcitabine, lycorine and oxysophoridine inhibit novel coronavirus (SARS-CoV-2) in cell culture

Ya-Nan Zhang  1   2 , Qiu-Yan Zhang  3   4 , Xiao-Dan Li  1   5 , Jin Xiong  1 , Shu-Qi Xiao  1 , Zhen Wang  6 , Zhe-Rui Zhang  1   2 , Cheng-Lin Deng  1 , Xing-Lou Yang  1 , Hong-Ping Wei  1 , Zhi-Ming Yuan  1 , Han-Qing Ye  1 , Bo Zhang  1   3   4   6
Affiliations

Gemcitabine, lycorine and oxysophoridine inhibit novel coronavirus (SARS-CoV-2) in cell culture

Ya-Nan Zhang et al. Emerg Microbes Infect. 2020 Dec.

Abstract

The emerging SARS-CoV-2 infection associated with the outbreak of viral pneumonia in China is ongoing worldwide. There are no approved antiviral therapies to treat this viral disease. Here we examined the antiviral abilities of three broad-spectrum antiviral compounds gemcitabine, lycorine and oxysophoridine against SARS-CoV-2 in cell culture. We found that all three tested compounds inhibited viral replication in Vero-E6 cells at noncytotoxic concentrations. The antiviral effect of gemcitabine was suppressed efficiently by the cytidine nucleosides. Additionally, combination of gemcitabine with oxysophoridine had an additive antiviral effect against SARS-CoV-2. Our results demonstrate that broad-spectrum antiviral compounds may have a priority for the screening of antiviral compounds against newly emerging viruses to control viral infection.

Keywords: 2019-nCoV; Novel coronavirus; SARS-CoV-2; alkaloid; broad-spectrum antiviral.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
The antiviral activities of gemcitabine, lycorine and oxysophoridine against SARS-CoV-2 in cell culture. (A) Dose-dependent inhibition of gemcitabine, lycorine and oxysophoridine on SARS-CoV-2 infectivity. Vero-E6 cells infected with SARS-CoV-2 at an MOI of 0.005 were treated with increasing concentration of compounds for 24 hours. Real-time RT-PCR was used to quantify viral RNA copy numbers in culture media. The cytotoxicity of the compounds on Vero-E6 cells was examined with CCK-8 assay kit. Antiviral activity and cytotoxicity are shown in pink and blue, respectively. The EC50 and CC50 are displayed in the upper right corner for each compound. At least three independent experiments were performed, and one representative experiment was presented. The data were represented as mean ± standard deviation (SD) of the triplicate measurements. (B) IFA analysis of the inhibition of the compounds on SARS-CoV-2 replication. At 24 hpi, the infected cells treated with different concentration of compounds were fixed and subjected to IFA using the primary antibody against NP protein of SARS-CoV-2. (C) Characterization of antiviral activities based on CPE-reduction assay. At 48 hpi, the CPE in infected Vero-E6 cells was visualized under light microscope. (D) Dose-dependent inhibition of gemcitabine, lycorine and oxysophoridine on SARS-CoV-2 infectivity in Huh-7 cells. The cells infected with SARS-CoV-2 at an MOI of 0.001 were treated with increasing concentration of compounds for 72 hours, and viral RNA copy numbers in culture media were quantified through real-time RT-PCR. The asterisks denote statistical differences between indicated groups.*p < 0.1, **p < 0.01, ***p < 0.001, ****p < 0.0001 (One-way ANOVA with Kruskal-Wallis test). n.s. indicates no statistical differences. (E) Additive anti-SARS-CoV-2 effect of gemcitabine in combination with different concentrations of oxysophoridine. The asterisks denote statistical differences between indicated groups.*p < 0.1, **p < 0.01, ***p < 0.001, ****p < 0.0001(Two-way ANOVA). n.s. indicates no statistical differences. (F) Suppression of the antiviral activity of gemcitabine by cytidine. Vero-E6 cells were infected with SARS-CoV-2 and simultaneously treated with 10 μM gemcitabine plus different concentrations of cytidine or uridine. The asterisks denote statistical differences between indicated groups.*p < 0.1, **p < 0.01, ***p < 0.001, ****p < 0.0001 (Student’s t-test). n.s. indicates no statistical differences. All above experiments were performed at least three independent, and one representative experiment was presented. All the Data were represented as mean ± standard deviation (SD).
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Grants and funding

This work was supported by the National Key Research and Development Program of China [grant number 2018YFA0507201].

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