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

doi:10.1016/j.isci.2022.105074

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

iScience. 2022 Oct 21;25(10):105074. doi: 10.1016/j.isci.2022.105074. Epub 2022 Sep 6.

Authors

Nunziata Maio¹, Sara Cherry², David C Schultz³, Brett L Hurst⁴, W Marston Linehan⁵, Tracey A Rouault¹

Affiliations

¹ Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
² Department of Pathology and Laboratory Medicine, Chemogenomic Discovery Program. University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
³ Department of Biochemistry and Biophysics, High-throughput Screening Core, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
⁴ Institute for Antiviral Research, Utah State University, Logan, UT 84322, USA.
⁵ Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

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.

Keywords: Health sciences; pharmacology; virology.