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Antiviral Efficacy of Pralatrexate against SARS-CoV-2
Joon-Yong Bae1, Gee Eun Lee1, Heedo Park1
1Department of Microbiology, Institute for Viral Diseases, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Abstract:
Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.
Insights
The anticancer drug pralatrexate effectively inhibited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in cell cultures. This study suggests pralatrexate as a potential drug repurposing candidate for treating coronavirus disease 2019 (COVID-19).
Area of Science:
- Virology
- Pharmacology
- Drug Discovery
Background:
- The global pandemic of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has led to significant health challenges.
- Limited availability of effective vaccines and antiviral treatments necessitates the exploration of alternative therapeutic strategies.
Purpose of the Study:
- To investigate the antiviral efficacy of the anticancer drug pralatrexate against SARS-CoV-2.
- To evaluate pralatrexate's potential for repurposing as a COVID-19 treatment.
Main Methods:
- Antiviral activity was assessed in Vero and human lung epithelial Calu-3 cell lines.
- Viral RNA levels and replication were measured following pralatrexate treatment.
- Cytotoxicity of pralatrexate was evaluated.
- Time-to-addition assays were performed to determine the optimal treatment window.
Main Results:
- Pralatrexate significantly reduced SARS-CoV-2 RNA copies in both cell types.
- Inhibition of viral replication was observed in a dose-dependent manner.
- No detectable cytotoxicity was associated with pralatrexate treatment at effective concentrations.
- Pralatrexate demonstrated inhibitory effects even when administered up to half a day post-infection.
Conclusions:
- Pralatrexate exhibits potent antiviral activity against SARS-CoV-2 in vitro.
- The drug's efficacy and favorable safety profile suggest its potential as a repurposed therapeutic for COVID-19.
- Further investigation into pralatrexate for COVID-19 treatment is warranted.
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