PropertyValue
?:abstract
  • The ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro and in vivo analyses, we report that Topoisomerase 1 (Top1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of Topotecan (TPT), a FDA-approved Top1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as four days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of Top1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing Top1 inhibitors for COVID-19 in humans.
is ?:annotates of
?:creator
?:doi
?:doi
  • 10.1101/2020.12.01.404483
?:journal
  • bioRxiv
?:license
  • biorxiv
?:pmid
?:pmid
  • 33299999.0
?:publication_isRelatedTo_Disease
is ?:relation_isRelatedTo_publication of
?:source
  • BioRxiv; Medline; WHO
?:title
  • Topoisomerase 1 inhibition therapy protects against SARS-CoV-2-induced inflammation and death in animal models
?:type
?:year
  • 2020-12-01

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