TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation
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View abstract on PubMed
Summary
This summary is machine-generated.Topoisomerase 1 (TOP1) inhibition effectively suppresses lethal inflammation caused by SARS-CoV-2 infection. This approach, using the drug topotecan (TPT), shows promise for treating severe COVID-19 and reducing mortality.
Area Of Science
- Virology
- Immunology
- Pharmacology
Background
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic impacts global health.
- Elevated inflammatory cytokines correlate with increased COVID-19 severity and mortality.
Purpose Of The Study
- Investigate the role of topoisomerase 1 (TOP1) in SARS-CoV-2-induced inflammation.
- Evaluate TOP1 inhibition as a potential host-directed therapy for severe COVID-19.
Main Methods
- Multidimensional analyses including epigenetic, transcriptional, in vitro, and in vivo studies.
- Therapeutic treatment with topotecan (TPT), an FDA-approved TOP1 inhibitor, in animal models.
Main Results
- TOP1 inhibition significantly suppresses SARS-CoV-2-induced lethal inflammation.
- TPT treatment reduced morbidity and rescued mortality in hamster and mouse models, even when administered 4 days post-infection.
Conclusions
- TOP1 inhibition represents a promising host-directed therapeutic strategy against severe SARS-CoV-2 infection.
- Repurposing TPT and its derivatives for COVID-19 warrants clinical trials due to their availability and low cost.
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