Maio Nunziata, Cherry Sara, Schultz David C, Hurst Brett L, Linehan W Marston, Rouault Tracey A
Molecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Pathology and Laboratory Medicine, Chemogenomic Discovery Program. University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
iScience. 2022 Oct 21;25(10):105074. doi: 10.1016/j.isci.2022.105074. Epub 2022 Sep 6.
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 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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）已引发全球大流行，即2019冠状病毒病（COVID-19）。除疫苗外，抗病毒疗法是应对COVID-19医疗措施的重要组成部分。我们之前报道过，小分子稳定氮氧化物TEMPOL通过导致其铁硫辅因子的氧化降解来使SARS-CoV-2的RNA依赖性RNA聚合酶（RdRp）失活。在此，我们证明TEMPOL在叙利亚仓鼠模型中可有效抑制病毒复制。在高风险暴露模型中，当在感染前2小时给药时，在动物身上观察到了TEMPOL对SARS-CoV-2复制的抑制作用。这些数据支持TEMPOL作为一种高效抗病毒药物用于人类对抗SARS-CoV-2感染的潜在应用。
