TEMPOL inhibits SARS-CoV-2 replication and development of lung disease in the Syrian hamster model

Nunziata Maio; Sara Cherry; David C. Schultz; Brett L. Hurst; W. Marston Linehan; Tracey A. Rouault

iScience (Oct 2022)

TEMPOL inhibits SARS-CoV-2 replication and development of lung disease in the Syrian hamster model

Nunziata Maio,
Sara Cherry,
David C. Schultz,
Brett L. Hurst,
W. Marston Linehan,
Tracey A. Rouault

Affiliations

Nunziata Maio: Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
Sara Cherry: Department of Pathology and Laboratory Medicine, Chemogenomic Discovery Program. University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
David C. Schultz: Department of Biochemistry and Biophysics, High-throughput Screening Core, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
Brett L. Hurst: Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA
W. Marston Linehan: Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
Tracey A. Rouault: Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author

Journal volume & issue: Vol. 25, no. 10
p. 105074

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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