. 2022 Sep 6;105074.
doi: 10.1016/j.isci.2022.105074. Online ahead of print.
TEMPOL inhibits SARS-CoV-2 replication and development of lung disease in the Syrian hamster model

Nunziata Maio 1 , Sara Cherry 2 , David C Schultz 3 , Brett L Hurst 4 , W Marston Linehan 5 , Tracey A Rouault 1



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. 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 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.