Work

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

Year: 2022

Type: article

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 are an important part of the healthcare response to COVID-19. Here, we report that TEMPOL, a stable nitroxide that inactivates the RNA-dependent RNA polymerase of SARS-CoV-2 by causing the oxidative degradation of its iron-sulfur cofactors, inhibits 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 hours 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.Funding Information: This work was supported by the Intramural Research Program of the National Institutes of Health (to T.A.R.) and by the Center for Cancer Research, National Cancer Institute (to W.M.L).Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: All animal studies were conducted in compliance with all relevant local, state, and federal regulations and were approved by the Bioqual Institutional Animal Care and Use Committee (IACUC).

Source: iScience

DOI: 10.1016/j.isci.2022.105074

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