학술논문
TEMPOL inhibits SARS-CoV-2 replication and development of lung disease in the Syrian hamster model.
Document Type
Academic Journal
Author
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.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
Subject
Language
English
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.
Competing Interests: The authors declare that they have no competing interests.
Competing Interests: The authors declare that they have no competing interests.