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TEMPOL inhibits SARS-CoV-2 replication and development of lung disease in the Syrian hamster model.
Maio, Nunziata; Cherry, Sara; Schultz, David C; Hurst, Brett L; Linehan, W Marston; Rouault, Tracey A.
  • Maio N; Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
  • Cherry S; Department of Pathology and Laboratory Medicine, Chemogenomic Discovery Program. University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Schultz DC; Department of Biochemistry and Biophysics, High-throughput Screening Core, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
  • Hurst BL; Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA.
  • Linehan WM; Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Rouault TA; Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
iScience ; 25(10): 105074, 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2007781
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide outbreak, known as coronavirus disease 2019 (COVID-19). Alongside vaccines, antiviral therapeutics is an important part of the healthcare response to COVID-19. We previously reported that TEMPOL, a small molecule stable nitroxide, inactivated the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 by causing the oxidative degradation of its iron-sulfur cofactors. Here, we demonstrate that TEMPOL is effective in vivo in inhibiting viral replication in the Syrian hamster model. The inhibitory effect of TEMPOL on SARS-CoV-2 replication was observed in animals when the drug was administered 2 h before infection in a high-risk exposure model. These data support the potential application of TEMPOL as a highly efficacious antiviral against SARS-CoV-2 infection in humans.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Vaccines Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2022.105074

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Vaccines Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2022.105074