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
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.
