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.

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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