TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation

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dc.contributor.authorHo, Jessica Sook Yuin
dc.contributor.authorMok, Bobo Wing-Yee
dc.contributor.authorCampisi, Laura
dc.contributor.authorJordan, Tristan
dc.contributor.authorYildiz, Soner
dc.contributor.authorParameswaran, Sreeja
dc.contributor.authorWayman, Joseph A.
dc.contributor.authorGaudreault, Natasha N.
dc.contributor.authorMeekins, David A.
dc.contributor.authorIndran, Sabarish, V
dc.contributor.authorMorozov, Igor
dc.contributor.authorTrujillo, Jessie D.
dc.contributor.authorFstkchyan, Yesai S.
dc.contributor.authorRathnasinghe, Raveen
dc.contributor.authorZhu, Zeyu
dc.contributor.authorZheng, Simin
dc.contributor.authorZhao, Nan
dc.contributor.authorWhite, Kris
dc.contributor.authorRay-Jones, Helen
dc.contributor.authorMalysheva, Valeriya
dc.contributor.authorThiecke, Michiel J.
dc.contributor.authorLau, Siu-Ying
dc.contributor.authorLiu, Honglian
dc.contributor.authorZhang, Anna Junxia
dc.contributor.authorLee, Andrew Chak-Yiu
dc.contributor.authorLiu, Wen-Chun
dc.contributor.authorJangra, Sonia
dc.contributor.authorEscalera, Alba
dc.contributor.authorAydillo, Teresa
dc.contributor.authorMelo, Betsaida Salom
dc.contributor.authorGuccione, Ernesto
dc.contributor.authorSebra, Robert
dc.contributor.authorShum, Elaine
dc.contributor.authorBakker, Jan
dc.contributor.authorKaufman, David A.
dc.contributor.authorMoreira, Andre L.
dc.contributor.authorCarossino, Mariano
dc.contributor.authorBalasuriya, Udeni B. R.
dc.contributor.authorByun, Minji
dc.contributor.authorAlbrecht, Randy A.
dc.contributor.authorSchotsaert, Michael
dc.contributor.authorGarcia-Sastre, Adolfo
dc.contributor.authorChanda, Sumit K.
dc.contributor.authorMiraldi, Emily R.
dc.contributor.authorJeyasekharan, Anand D.
dc.contributor.authorTenOever, Benjamin R.
dc.contributor.authorSpivakov, Mikhail
dc.contributor.authorWeirauch, Matthew T.
dc.contributor.authorHeinz, Sven
dc.contributor.authorChen, Honglin
dc.contributor.authorBenner, Christopher
dc.contributor.authorRicht, Juergen A.
dc.contributor.authorMarazzi, Ivan
dc.date.accessioned2025-01-20T23:50:56Z
dc.date.available2025-01-20T23:50:56Z
dc.date.issued2021
dc.description.abstractThe 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), an FDA-approved TOP1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as 4 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 severe coronavirus disease 2019 (COVID-19) in humans.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.cell.2021.03.051
dc.identifier.eissn1097-4172
dc.identifier.issn0092-8674
dc.identifier.urihttps://doi.org/10.1016/j.cell.2021.03.051
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94750
dc.identifier.wosidWOS:000652830800009
dc.issue.numero10
dc.language.isoen
dc.pagina.final+
dc.pagina.inicio2618
dc.revistaCell
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleTOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation
dc.typeartículo
dc.volumen184
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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