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Methotrexate inhibits SARS-CoV-2 virus replication "in vitro"
Arnaldo Caruso1, Francesca Caccuri1, Antonella Bugatti1
1Department of Molecular and Translational Medicine, Section of Microbiology and Virology, University of Brescia Medical School, Brescia, Italy.
Journal of Medical Virology
|September 14, 2020
Summary
Methotrexate, an existing drug, effectively inhibits SARS-CoV-2 replication by targeting host ribonucleotide pathways. Early treatment with methotrexate may prevent severe COVID-19 complications.
Area of Science:
- Virology
- Pharmacology
- Infectious Diseases
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in significant mortality and economic impact.
- Current treatments for COVID-19 focus on medical complications, with no specific antiviral therapies or vaccines available.
Purpose of the Study:
- To identify host-encoded pathways crucial for viral RNA synthesis as potential therapeutic targets.
- To evaluate the antiviral efficacy of methotrexate, an inhibitor of purine biosynthesis, against SARS-CoV-2.
Main Methods:
- A systems biology approach was employed to identify host targets.
- In vitro experiments assessed the effect of methotrexate on viral RNA replication, protein synthesis, and virus release.
Main Results:
- Methotrexate potently inhibited SARS-CoV-2 RNA replication, viral protein synthesis, and virus release.
- Effective antiviral concentrations of methotrexate were comparable to those used in established human therapies.
Conclusions:
- Targeting host ribonucleotide supply pathways is a viable strategy against SARS-CoV-2.
- Methotrexate demonstrates significant antiviral activity and could be a valuable therapeutic option for early COVID-19 treatment to prevent severe outcomes.

