ArticleCell2021
TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation.
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Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78citing papers in PubMed
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Who cites it
78 citing papers in PubMed, 121 citations in OpenAlex.
- Topoisomerase-mediated resolution of negative DNA supercoiling sustains human transcription and gene activation.bioRxiv : the preprint server for biology · 2026Article
- Targeting FAR1 to inhibit intestinal macrophage ferroptosis: repurposing irinotecan as a novel sepsis therapy.Apoptosis : an international journal on programmed cell death · 2026Article
- High-resolution promoter interaction analysis implicates genes involved in activation of type 3 innate lymphoid cells in immune disease risk.Nature genetics · 2026Article
- Deltacoronavirus Modulates circRNA cGLIS3 Metabolism to Evade Host Antiviral Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting DNA Topoisomerase I for the Treatment of Cancer: Past, Present and Future.Journal of molecular biology · 2026Review
- Global reorganization of genome architecture at the transition to gametogenesis.Nature structural & molecular biology · 2026Article
- Multidimensional transcriptome dataset for systematic evaluation of Jakyakgamcho-tang-induced cell signatures.Scientific data · 2026Article
- A convenient single-cell assay for the newly synthesized transcriptome reveals FLI1 regulon downregulation during T cell activation.Cell reports methods · 2026Article
- The Function of Microglia in Cognitive Impairment Influenced by Sleep Deprivation.Cellular and molecular neurobiology · 2026Review
- High-resolution promoter interaction analysis implicates genes involved in the activation of Type 3 Innate Lymphoid Cells in autoimmune disease risk.bioRxiv : the preprint server for biology · 2026Article
- Cognitive dysfunction in type 1 diabetes: role of TREM2 in microglial activation and Aβ pathology.Journal of neuroinflammation · 2026Article
- Changes in gene expression levels caused by H3K9me3/H3K9ac modifications are associated with BmCPV infection inVirulence · 2025Article
- The gene regulatory landscape driving mouse gonadal supporting cell differentiation.Science advances · 2025Article
- Substituted Triazole-3,5-Diamine Compounds as Novel Human Topoisomerase III Beta Inhibitors.International journal of molecular sciences · 2025Article
- Neopterin mediates sleep deprivation-induced microglial activation resulting in neuronal damage by affecting YY1/HDAC1/TOP1/IL-6 signaling.Journal of advanced research · 2025Article
- Serum proteomic approach to identifying differentially expressed proteins in effusive feline infectious peritonitis.Scientific reports · 2025Article
- ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage.Nature structural & molecular biology · 2025Article
- MicroRNA-24-3p targeting Top1 in perirenal fat is involved in circulating inflammation and high cardiovascular disease risk in patients with primary aldosteronism.Journal of translational medicine · 2025Article
- Genetic coupling of enhancer activity and connectivity in gene expression control.Nature communications · 2025Article
- Applying 3D Genome Technology in Virology Research.Methods in molecular biology (Clifton, N.J.) · 2025Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
53 authors at 14 institutions in 6 countries.
Jessica Sook Yuin HoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Bobo Wing-Yee MokDepartment of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine (HKUMed), The University of Hong Kong, Hong Kong.
Laura CampisiDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Tristan JordanDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Soner YildizDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sreeja ParameswaranCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Joseph A WaymanDivisions of Immunobiology and Biomedical Informatics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Natasha N GaudreaultDiagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA.
David A MeekinsDiagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA.
Sabarish V IndranDiagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA.
Igor MorozovDiagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA.
Jessie D TrujilloDiagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA.
Yesai S FstkchyanDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Raveen RathnasingheDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Zeyu ZhuDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Simin ZhengDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Nan ZhaoDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Kris WhiteDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Helen Ray-JonesMRC London Institute of Medical Sciences, London W12 0NN, UK.
Valeriya MalyshevaMRC London Institute of Medical Sciences, London W12 0NN, UK.
Michiel J ThieckeEnhanc3D Genomics Ltd, Cambridge CB22 0AT, UK.
Siu-Ying LauDepartment of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine (HKUMed), The University of Hong Kong, Hong Kong.
Honglian LiuDepartment of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine (HKUMed), The University of Hong Kong, Hong Kong.
Anna Junxia ZhangDepartment of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine (HKUMed), The University of Hong Kong, Hong Kong.
Andrew Chak-Yiu LeeDepartment of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine (HKUMed), The University of Hong Kong, Hong Kong.
Wen-Chun LiuDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sonia JangraDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Alba EscaleraDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Teresa AydilloDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Betsaida Salom MeloDepartment of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ernesto GuccioneTisch Cancer Institute, Department of Oncological Sciences and Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Robert SebraDepartment of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Sema4, a Mount Sinai venture, Stamford, CT, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Elaine ShumDivision of Medical Oncology and Hematology, NYU Langone Perlmutter Cancer Center, New York, NY 10016, USA.
Jan BakkerPontificia Universidad Católica de Chile, Santiago, Chile; Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Editor in Chief, Journal of Critical Care, NYU School of Medicine, Columbia University College of Physicians & Surgeons, New York, NY, USA.
David A KaufmanDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU School of Medicine, New York, NY, USA.
Andre L MoreiraDepartment of Pathology, New York University School of Medicine, New York, NY, USA.
Mariano CarossinoLouisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Udeni B R BalasuriyaLouisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Minji ByunDepartment of Medicine, Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Randy A AlbrechtDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Michael SchotsaertDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Adolfo Garcia-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Department of Oncological Sciences and Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
Sumit K ChandaImmunity and Pathogenesis Program, Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Emily R MiraldiDivisions of Immunobiology and Biomedical Informatics, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA.
Anand D JeyasekharanDepartment of Haematology-Oncology, National University Hospital and Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore, Singapore.
Benjamin R TenOeverDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Virus Engineering Center for Therapeutics and Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mikhail SpivakovMRC London Institute of Medical Sciences, London W12 0NN, UK.
Matthew T WeirauchCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229, USA; Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Sven HeinzDepartment of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92092, USA.
Honglin ChenDepartment of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine (HKUMed), The University of Hong Kong, Hong Kong.
Christopher BennerDepartment of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92092, USA.
Juergen A RichtCenter of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD), Kansas State University, Manhattan, KS, USA; Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA.
Ivan MarazziDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: ivan.marazzi@mssm.edu.
Icahn School of Medicine at Mount Sinai · USHKU-Pasteur Research Pole · HKKansas State University · USCincinnati Children's Hospital Medical Center · USMRC London Institute of Medical Sciences · GBLouisiana State University · USNew York University · USUniversity of California San Diego · USGenomics (United Kingdom) · GBNational University of Singapore · SGNYU Langone Health · USPontificia Universidad Católica de Chile · CLSanford Burnham Prebys Medical Discovery Institute · USSema4 (United States) · US
Funding
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4MSARS-CoV adaptations through a Systems Biology Lens (SYBIL)U19AI135972 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Adolfo Garcia-Sastre · 2018 to 2026
$27.2MSex-specific effects of obestity on Influenza A virus infection and immunityP20GM130448 · NIGMS · KANSAS STATE UNIVERSITY · PI Jakob Trimpert · 2020 to 2026
$15.8MDynamic regulatory network models of human response to influenza virusU01AI150748 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI MARAZZI, IVAN, MIRALDI, EMILY · 2020 to 2024
$5.8MA host-dependent mechanism controlling influenza virus infection by suppressing viral RNA synthesisR01AI143840 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MARAZZI, IVAN · 2019 to 2023
$2.1MBig Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0MUncovering how transcription and chromatin 3D structure impact one another during cellular activationR01GM134366 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BENNER, CHRISTOPHER W · 2019 to 2023
$1.7MHow transcription disrupts genome 3D organizationR01GM129523 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HEINZ, SVEN W · 2020 to 2023
$1.3MMedical Research Council MC_UP_1605/3NIAID NIH HHS HHSN272201400006CNIAID NIH HHS HHSN272201400008CNIAID NIH HHS R01 AI143840NIAID NIH HHS U01 AI150748NIAID NIH HHS U19 AI135972NIDDK NIH HHS P30 DK063491NIGMS NIH HHS P20 GM130448NIGMS NIH HHS R01 GM129523NIGMS NIH HHS R01 GM134366NIH HHS S10 OD026880
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), 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.
Indexed as
COVID-19 Drug TreatmentAnimalsChlorocebus aethiopsCOVID-19DNA Topoisomerases, Type IHumansInflammationMesocricetusMiceMice, TransgenicSARS-CoV-2THP-1 CellsTopoisomerase I InhibitorsTopotecanVero CellsDNA Topoisomerases, Type ITOP1 protein, humanTopoisomerase I InhibitorsTopotecanchromatinCOVID-19cytokine stormepigeneticsinducible genesinflammationSARS-CoV-2topoisomerasetopotecantranscription
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